NZ778303B2

NZ778303B2 - Systems and Methods for Ex- Vivo Organ Care

Info

Publication number: NZ778303B2
Application number: NZ778303A
Authority: NZ
Inventors: Hossam Algamil; Richard Bringham; David Carpenter; Giovanni Cecere; Ahmed Elbetanony; Robert Fishman; Lawrence Goff; Waleed Hassanein; Tamer Khayal; Stanley Kyi
Original assignee: Transmedics Inc
Filing date: 2005-10-07
Publication date: 2023-11-28

Abstract

Disclosed is a method of ex-vivo organ preservation at physiologic or near-physiologic conditions. The method comprises placing an ex-vivo organ in a chamber of an organ care system; connecting the ex-vivo organ to a perfusion fluid circuit; opening an outer lid of the chamber of the organ care system to examine the ex-vivo organ through a flexible membrane of the organ care system. A perfusion fluid is pumped to the ex-vivo organ via the perfusion fluid circuit. The ex-vivo organ is tested for one of measuring, with respect to the ex-vivo organ, an arterial blood gas level or a metabolite level, or measuring a flow rate of the perfusion fluid, a pressure of the perfusion fluid, or a temperature of the perfusion fluid, or a pressure volume loop evaluation. A setting of the organ care system in response to a result of the testing; and after adjusting the setting of the organ care system in response to the result of the testing, re-testing the ex-vivo organ or the organ care system, where the adjusted setting is one of a flow rate of the perfusion fluid, a pressure of the perfusion fluid, a temperature of the perfusion fluid, an oxygenation level of the perfusion fluid, and a nutritional level of the perfusion fluid, or applying, via one or more electrodes positioned between the ex-vivo organ and a pad in the organ care system, a defibrillation signal to the ex-vivo organ.

Description

Disclosed is a method of ex-vivo organ preservation at physiologic or near-physiologic ions.

The method comprises placing an ex-vivo organ in a chamber of an organ care system; connecting the ex-vivo organ to a perfusion fluid circuit; opening an outer lid of the chamber of the organ care system to examine the ex-vivo organ through a flexible membrane of the organ care system.

A perfusion fluid is pumped to the ex-vivo organ via the perfusion fluid circuit. The o organ is tested for one of measuring, with respect to the o organ, an arterial blood gas level or a metabolite level, or measuring a flow rate of the perfusion fluid, a pressure of the perfusion fluid, or a temperature of the perfusion fluid, or a pressure volume loop evaluation. A setting of the organ care system in response to a result of the testing; and after adjusting the g of the organ care system in se to the result of the testing, ting the ex-vivo organ or the organ care system, where the adjusted setting is one of a flow rate of the perfusion fluid, a pressure of the perfusion fluid, a temperature of the perfusion fluid, an oxygenation level of the perfusion fluid, and a nutritional level of the perfusion fluid, or applying, via one or more electrodes positioned between the o organ and a pad in the organ care system, a defibrillation signal to the ex-vivo organ. 778303 B2 Systems and Methods for Ex- Vivo Organ Care The present application is a divisional application of New Zealand Application No. , which is incorporated in its entirety herein by reference.

Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/616,835, filed on October 7, 2004; U.S. Provisional Patent Application Serial No. 60/694,971, filed on June 28, 2005; and U.S. Provisional Patent Application filed on October 6, 2005, and ed Systems and Methods for Ex-Vivo Organ Care. The specifications of each of the foregoing are incorporated by reference herein in their entirety.

Field of the Invention The ion generally relates to s, methods, and devices for ex-vivo organ care. More particularly, in various ments, the invention relates to caring for an organ ex-vivo at physiologic or near-physiologic conditions.

Background of the Invention Current organ preservation techniques typically involve hypothermic storage of the organ in a chemical perfusate solution on ice. In the case of a heart, it is typically arrested, and cooled with the storage/cardioplegic solution in a hypothermic, nonfunctioning state. These ques utilize a variety of plegic solutions, none of which sufficiently protect the heart from myocardial damage resulting from ischemia.

Such injuries are particularly undesirable when an organ, such as a heart, is intended to be transplanted from a donor into a recipient. In addition to myocardial damage resulting from ischemia, reperfusion of a heart may exacerbate the myocardial injury and may cause coronary vascular endothelial and smooth muscle injury, which may lead to ry vasomotor dysfunction.

Using conventional approaches, such injuries increase as a on of the length of time an organ is maintained ex-vivo. For example, in the case of a heart, typically it may be ined o for only a few hours before it becomes unusable for transplantation. This relatively brief time period limits the number of recipients who can be reached from a given donor site, thereby restricting the ent pool for a harvested heart. Even within the few hour time limit, the heart may nevertheless be significantly damaged. A significant issue is that there may not be any apparent indication of the damage. Because of this, less-than-optimal organs may be transplanted, ing in post- transplant organ dysfunction or other injuries. Thus, it would be desirable to develop techniques that can extend the time during which an organ can be preserved in a healthy state o. Such techniques would reduce the risk of transplantation failure and enlarge potential donor and recipient pools.

Effective preservation of an ex-vivo organ would also provide numerous other benefits.

For instance, prolonged ex-vivo preservation would permit more careful monitoring and functional testing of the harvested organ. This would in turn allow earlier detection and potential repair of defects in the harvested organ, further reducing the likelihood of transplantation failure. The ability to m simple repairs on the organ would also allow many organs with minor defects to be saved, whereas current transplantation techniques require them to be discarded.

In addition, more effective matching between the organ and a ular recipient may be achieved, further reducing the likelihood of eventual organ rejection. Current transplantation techniques rely mainly on matching donor and recipient blood types, which by itself is a relatively unreliable indicator of whether or not the organ will be rejected by the recipient. A more preferred test for organ compatibility is a Human Leukocyte Antigen (HLA) matching test, but current cold ischemic organ preservation approaches de the use of this test, which can often e 12 hours or more to complete.

Prolonged and le ex-vivo organ care would also provide benefits e the context of organ transplantation. For e, a patient's body, as a whole, can typically tolerate much lower levels of , bio- and radiation therapy than many particular organs.

An ex-vivo organ care system would permit an organ to be removed from the body and treated in isolation, reducing the risk of damage to other parts of the body.

In view of the foregoing, improved systems, methods, and devices for caring for an organ ex-vivo are needed.

Summary of the Invention In a first aspect, the present disclosure provides a method comprising: placing an ex-vivo organ in a chamber of an organ care system; connecting the ex-vivo organ to a perfusion fluid circuit of the organ care system; opening an outer lid of the chamber of the organ care system; ing the o organ through a flexible membrane of the organ care system; pumping, via the perfusion fluid circuit, a perfusion fluid to the ex-vivo organ; testing the ex-vivo organ or the organ care ; (42146317_1):SAK adjusting a setting of the organ care system in response to a result of the testing; and after adjusting the setting of the organ care system in response to the result of the testing, retesting the ex-vivo organ or the organ care system.

In a second aspect, the present disclosure es a method according to the first aspect of the disclosure, substantially as herein described with reference to any one or more of the examples or figures.

The invention addresses the deficiencies in the prior art by, in various embodiments, ing ed systems, s and devices relating to portable ex- vivo organ care.

More particularly, ing to various aspects, the invention provides systems, methods and devices relating to portable ex-vivo heart care. According to one advancement, the heart care system of the invention maintains the heart in a beating state at, or near, normal physiological conditions. To this end, the system circulates an 2a followed by page 3 oxygenated, nutrient enriched perfusion ?uid to the heart at or near physiological ature, pressure and ?ow rate. According to one entation, the system employs a blood product-based perfusion ?uid to more accurately mimic normal physiologic ions. In alternative embodiments, the system uses a synthetic blood substitute solution, while in other embodiments, the solution may n a blood product in combination with a blood substitute product.

According to another advancement, the system of the invention can in a harvested heart in two modes of operation; a normal aortic ?ow mode (also referred to as "normal ?ow mode"), and a retrograde aortic flow mode (also referred to as a "retrograde ?ow mode"). Generally, in the normal flow mode, the system circulates the perfusion ?uid to the heart in the same manner as blood would circulate in the human body. More particularly, the perfusion fluid enters the heart via the left atrium and is ?owed away from the heart via the right and left ventricles. In normal ?ow mode, the system pumps the perfusion ?uid to the heart at a rate of between about 1 liter/min and about 5 liters/minute.

This mode is useful, for example, for performing functional testing to verify that the heart is defect free, both prior and subsequent to transportation to a donor location.

Altematively, in retrograde flow mode, the system flows the perfusiOn ?uid into the heart via the aorta, through the coronary sinus, and then out ofthe heart via the right ventricle.

In this mode of operation, the system reduces the ?ow rate of the perfusion fluid to 2O between about 300 iters/min and about 1 liter/min. The inventors have found that the retrograde flow path, along with the reduced ?ow rate, s damage to the heart during extended periods of ex-vivo care. Thus, according to one feature ofthe invention, the heart is transported to a donor site in retrograde flow mode.

According to various aspects, the systems and/or devices of the invention include, and!or the methods ofthe invention employ, one or more of: an organ chamber assembly for containing a heart during ex—vivo care; a oir for containing and optionally, defoaming and/or ?ltering a volume ofperfusion ?uid; a ion ?uid pump for pumping/circulating perfusion fluid to and from the ted heart; a heater assembly for maintaining the temperature ofthe perfusion ?uid at or near physiological temperatures; a ?ow mode selector valve for switching between normal and retrograde ?ow modes; an oxygenator for re-oxygenating the perfusion ?uid subsequent to it being expelled by the heart; a nutritional subsystem for replenishing nts in the ion ?uid as they are metabolized by the heart and for providing preservatives to the per?ision ?uid to reduce, for example, isohemia and/or other reperfusion related injuries to the heart; a sensor subsystem for monitoring, for example, temperature, re, flow rate and/or oxygenation of the perfusion ?uid, and/or electrical signals ?rom the heart and/or the various components employed to maintain suitable flow ions to and hem the heart; an or interface for assisting an operator in monitoring system operation and/or the condition of the heart, and/or for enabling the operator to set various operating parameters; a power subsystem for providing fault tolerant power to the organ care system; and a control subsystem for controlling operation of the organ care system.

Operationally, in one practice, a heart is harvested from a donor and af?xed to the organ chamber ly by a process of cannulation. The perfusion ?uid pump pumps ion ?uid from a reservoir to the heater assembly. The heater assembly heats the perfusion fluid to or near a normal physiological temperature. According to one embodiment, the heater assembly heats the perfusion ?uid to between about 32° C and about 37° C. From the heater assembly, the ion ?uid ?ows to the ?ow mode selector valve. Initially, the ?ow mode selector valve is positioned for retrograde ?ow mode to direct the perfusion ?uid from the heater assembly to a ?rst interface on the organ chamber assembly. Also referred to as an aorta interface or the left ventricle interface, the ?rst interface is ated to vascular tissue of the left ventricle (e.g., an aorta stub) via a conduit d within the organ chamber assembly. The heart then pumps the perfusion ?uid out of the heart through the right ventricle via a second interface on the organ chamber assembly. The second interface, also referred to as a pulmonary artery interface or right ventricle interface, is cannulated to vascular tissue of the right ventricle (cg, a pulmonary artery stub) via a t located within the organ chamber assembly. In retrograde ?ow mode, fluid is not pumped into or out of the left side of the heart other than in the form of a small trickle ofperfusion ?uid, which is delivered to moisten the left atrium. In se to the flow mode selector valve being in the normal ?ow mode position, it directs the perfusion fluid into the left atrium of the heart via a third interface on the organ chamber assembly. The third interface, also ed to as a pulmonary vein interface or left atrium interface, is cannulated to the vascular tissue ofthe left atrium (e.g, a pulmonary vein stub) via a conduit located within the organ chamber assembly. The heart then expels the perfusion fluid through the left cle via the aorta interface, and through the right ventricle via the puhnonary artery interface.

In both modes ofoperation, from the ary artery interface, the per?rsion ?uid ?ows into the oxygenator. The oxygenator es oxygen ?om an external or onboard gas source and s gas (cg, ) to the perfusion ?uid prior to returning it to the reservoir. The system may e one or more oxygen saturation sensors to measure the oxygen saturation level ofthe perfusion ?uid to ensure that the perfusion ?uid is maintained at physiological oxygen levels. In the embodiments where the perfusion ?uid is blood~product based, it contains red blood cells (i.e., oxygen ng cells).

Optionally, the oxygen sensors also provide a hematocrit measurement of the concentration of red blood cells in the ion ?uid.

In both normal and retrograde ?ow modes, the nutritional subsystem infuses the perfusion ?uid with a supply ofmaintenance solutions as the perfusion ?uid ?ows through the system, and in some embodiments, while it is in the reservoir. According to one feature, the maintenance solutions e nutrients, such as glucose, ing to another feature, the maintenance solutions include a supply oftherapeutics and/or preservatives (e.g., cardio stimulants, insulin, amino acids, etc.) for reducing ischemia and/or other reperfusion related es to the heart.

According to another practice, the per?lsion ?uid includes blood removed from the donor through a process of exsanguination during harvesting of the heart. Initially, the blood from the donor is loaded into the reservoir and the cannulation locations in the organ chamber assembly are bypassed with a bypass conduit to enable normal mode flow of perfusion ?uid through the system without a heart being present. Prior to cannulating the harvested heart, the system may be primed by circulating the exsanguinated donor blood through the system to heat, oxygenate and/or ?lter it. Nutrients, preservatives, and/or other therapeutics may also be provided during priming via the infusion pump of the nutritional subsystem. During priming, various ters may also be initialized and calibrated via the operator interface during priming. Once primed and g appropriately, the pump flow is reduced or cycled off, the bypass conduit is removed from the organ chamber assembly, and the heart is cannulatecl into the organ chamber assembly.

The pump flow is then restored or increased, as the case may be. According to one feature, the operator interface may be d into the system via a hard wired connection, or may be unplugged and used to wirelessly communicate with the system of the invention.

According to one feature, the system includes a plurality of compliance chambers.

The ance chambers are essentially small inline ?uid accumulators with ?exible, resilient walls for simulating the human body’s vascular compliance by aiding the system in more accurately ing blood ?ow in the human body, for example, by providing flow back-pressure and70r by ?ltering/reducing ?uid pressure spikes due, for example, to ?ow rate changes. In one ration, compliance chambers are located on either side of the ?ow mode selector valve and on the output of the perfusion ?uid pump. According to one feature, a compliance chamber is located next to a clamp used for regulating back pressure seen by the aorta during normal ?ow mode operation.

According to one implementation, the sensor subsystem includes an electrocardiogram (ECG) sensor for monitoring ical signals from the heart.

According to one embodiment, the control subsystem synchronizes the pumping of the perfusion ?uid to the heart with the ECG s. According to one feature, the ECG signals include an r—wave, and the control subsystem uses the r—wave to synchronize the ?uid pumping with a diastolic state of the heart. According to another feature, the control tem adjusts pump stroke volume and/or pump rate in dependence on the ECG signals. For e, in one embodiment, the control subsystem reduces the pump stroke volume as heart rate increases in order to in blood ?ow. In another embodiment, the system reduces the pump stroke volume in response to detecting an irregular heart rate.

In both cases, the result is to reduce fluid volume pumped to the heart, which in turn reduces the likelihood ofcausing damage to the heart. In various embodiments, the sensors include perfusion ?uid ?ow rate and/or ?ow pressure sensors, which provide feedback for controlling the perfusion ?uid pump. According to one embodiment, to more tely simulate normal circulation through the body, the pump ofthe system is a pulsatile pump.

According to one aspect of the invention, the organ chamber ly includes a plurality of improved features. More ularly, in one con?guration, the organ chamber assembly of the invention includes a housing, an outer lid and an intermediate lid. The housing includes a bottom and one or more walls for containing the organ. The intermediate lid covers an opening to the housing for ntially enclosing the organ within the housing, and includes a frame and a ?exible membrane suspended within the frame. The ?exible membrane, preferably, is transparent but may be opaque, translucent, 0r substantially transparent. According to one feature, the ?exible ne includes suf?cient excess membrane material to contact an organ contained within the chamber.

This feature enables a medical Operator to touch/examine the organ indirectly through the membrane while still maintaining sterility ofthe system and the organ. The outer lid opens and closes over the intermediate lid independently from the intermediate lid.

Preferably, the outer lid is rigid enough to protect the organ from al contact, indirect or direct.

According to one implementation, the ediate lid is hinged to the housing.

The intermediate lid may also e a latch for securing the ediate lid closed over the opening ofthe organ chamber. The outer lid may be similarly hinged and latched. In some con?gurations, gaskets are provided for forming a ?uid seal between the intermediate lid frame and the one or more organ chamber walls, and/or for forming a ?uid seal between the periphery ofthe outer lid and the frame ofthe intermediate lid.

Optionally, the organ chamber assembly includes a pad or a sac assembly sized and shaped for irner?tting Within a bottom ofthe g. Preferably, the pad ly includes a pad formed from a material ent enough to rl the organ from mechanical vibrations and shocks during transport. In the case of the organ chamber assembly being con?gured to receive a heart, according to one e, the pad of the invention includes a mechanism for receiving at least one electrode. The mechanism may include, without limitation, one or more slots, indentations, protrusions, through apertures, partially through res, hooks, eyelets, snaps, adhesive patches, or the like. According to one advantage, the mechanism allows for adjustable placement of the at least one electrode on or in the pad to accommodate differently sized and shaped hearts. According to one embodiment, the pad includes a through~aperture through which an ical lead of_the at least one electrode may pass. ing to one embodiment, the pad assembly includes at least one electrode adjustably positioned at a location on or in the pad in such a way as to facilitate contact with a heart placed on the pad in the organ chamber assembly. According to one con?guration, the at least one electrode rests on the e ofthe pad and is held in place by the weight ofthe heart. In another con?guration, the at least one electrode is glued to the e ofthe pad. The at least one electrode includes One or more sensors for monitoring one or more electrical signals from the heart. It may also include one or more de?brillator contacts for providing an electrical signal to the heart. One advantage ofthe pad/electrode con?guration of the invention is that it does not require the at least one electrode to be permanently or temporarily sutured or otherwise mechanically connected to the heart. Instead, ical tion is made by placing the heart on the one or more electrodes. In one con?guration, the at least one electrode includes an integrated sensor and de?brillation contact that allows the user to monitor ical signals from the heart and provide an ical signal to the heart through a common electrical interface connection to the organ chamber assembly. According to another feature, the common electrical interface includes one or more electrical ports on the organ chamber ly for transferring electrical signals between the at least one electrode Within the chamber and instrumentation located external to the housing. By way ofexample, the ports may e the ECG s to an external sor and/or display, and/or may provide de?brillation power to the electrodes.

Optionally, the organ chamber housing also includes a base for angling the g for optimal heart function. According to one feature, the base maintains a heart contained within the organ chamber at an angle of between about 30° and about 60° relative to l5 horizontal.

According to another , the perfusion ?uid heater assembly of the invention includes a plurality of improved features relating to providing a compact, solid state mechanism for heating the perfusion ?uid. Some features ofthe heater assembly make it particularly suitable for g blood-product based embodiments of the per?rsion ?uid.

In one embodiment, the heater assembly ofthe invention includes an inlet, an outlet, a ?ow channel, ?rst and second ?ow channel plates and a ?rst heater. The ?ow channel is formed between the ?rst and second ?ow channel . The inlet flows the perfusion ?uid into the ?ow channel and the outlet flows the perfusion ?uid out ofthe . The ?rst and second flow channel plates have substantially bioinert perfusion ?uid contacting surfaces for providing direct contact with the perfusion fluid ?owing through the channel.

The ion ?uid contacting surfaces may be formed, for example, from a treatment or g on a substrate or may be the substrate surface itself. The ?rst heater is thermally coupled to the ?rst flow channel plate for heating the ?rst flow channel plate. In one ration, the ?rst heater is located on a nonpcrfusion ?uid contacting side of the ?rst ?ow channel plate. According to a further embodiment, the heater assembly of the invention also includes a second heater thermally coupled to the second flow channel plate for heating the second ?ow channel plate to provide a more uniform temperature distribution in the ?ow channel.

According to one con?guration, the heater assembly includes a ?rst heater plate disposed between the ?rst heater and the ?rst ?ow channel plate for thermally coupling heat from the ?rst heater to the ?rst ?ow l plate. According to one e, the ?rst heater plate is formed from a material, such as aluminum, that conducts and distributes heat fmm the heater relatively uniformly. The unifome uted heat ofthe heater plate is then coupled to the ?rst channel plate, which preferably is formed ?om a bioinert material, such as titanium, which does not necessarily provide suf?ciently uniform heat distribution ifput in direct contact With the heater. The heater assembly may also include a second heater plate ed between the second heater and the second ?ow channel plate for coupling heat from the second heater to the second ?ow channel plate.

According to one embodiment, the ?rst and/or second heaters ofthe ion are resistive heaters. In one con?guration, they each include a resistive heating element formed on a polyimide substrate. ing to a further ration, the resistive g elements have a resistance of about 5 ohms. In other con?gurations, the resistance of the heating elements ranges from about 3 ohms to about 10 ohms.

Optionally, the heater assembly of the invention includes one or more temperature sensors. For e, the heater ly may include a temperature sensor at its outlet for reporting the temperature of the perfusion ?uid exiting the heater to the control subsystem. The signal from this sensor may be employed in a feedback loop to l drive signals to the ?rst and second heaters to control the temperature of the heater plates.

Additionally, to ensure that the perfusion ?uid contacting surfaces of the heater plates do not reach a temperature that might damage the perfusion fluid, the heater assembly may also include temperature s for reporting the temperature ofthe ?rst and/or second s to the control subsystem. The signals from these sensors may also be employed in a feedback 100p to further control the drive signals to the ?rst and/or second heaters to limit the maximum temperature of the heater plates. According to a variation of this ment, the heater assembly may include temperature sensors for reporting the temperature of the ?rst and/or second heaters to the control subsystem.

To provide improved contact between the ?rst and/or second heaters and their respective heater plates, and also between the ?rst and/or second heater plates and their respective flow channel plates, the heater assembly may also include ?rst and second resilient pads disposed on the respective heaters for maintaining the ?rst heater in contact with the ?rst heater plate and the second heater in contact with the second heater plate in response to compressive force. The compressive force may be provided, for example, by way of one or more heater assembly housing components. According to one feature, the heater assembly includes housing components formed from a polycarbonate, and weighs less than about 5 1b, while in other ments the heater assembly may weigh less than about 4 lb, less than about 3 11), less than about 2 lb, or even less than about 1 lb.

According to another feature, the heater assembly is about 6.75 inches long, about 2.75 inches wide, and about 2.5 inches thick, all exclusive of inlet and outlet ports and temperature sensor lies. ing to another feature, the heater assembly is a single use disposable assembly.

According to one embodiment, in operation, the heater assembly uses n about 1 Watt and abOut 200 Watts of power. According to a further embodiment, the heater assembly ofthe invention is sized and shaped to transition about 2.5 liters of perfusion ?uid ?owing through the channel at a rate ofbetween about 300 nil/min and about 5 L/min from atemperature of less than about 30 °C to a temperature of about 37 °C in less than about 25 minutes, less than about 20 minutes, less than about 15 s or even less than about 10 minutes, without causing substantial hemolysis to the blood cells or denaturation of any proteins that may be contained in the perfusion ?uid.

According to a further embodiment, the power subsystem ofthe invention provides a fault tolerant battery arrangement. More particularly, a plurality ofbatteries are ocked such that all of them may not be removed from the system at any ular time while the system is operating to maintain an organ. According to one feature, the power subsystem can switch between external power and d battery backup, without interruption of system operation. According to another feature, the power subsystem tically allocates externally supplied power between powering the system, ng the batteries, and charging internal batteries ofthe wireless or interface. ing to another aspect, the invention segments various subsystems and components ofthe portable organ care system into two modules; a portable multiple use module and a single use able module. According to one segmentation, the system of the invention generally assigns perfusion ?uid contacting (and thus, blood product contacting in embodiments employing a blood product perfusion fluid) components to the disposable module, and non perfusion-?uid—contacting (and thus, non~blood t contacting components) to the multiple use module. However, the disposable unit may also include non—blood contacting components. ing to one feature, the perfusiOn— ?uid contacting components may be coated or bonded with heparin or other anticoagulant or biocompatible material to reduce the in?ammatory se that may otherwise arise when the perfusion fluid contacts the surfaces ofthe components. Heparin may also be added to the maintenance solutions for circulation within the system.

In one embodiment, the portable multiple use module includes a le housing constructed on a portable chassis, and the single use disposable module includes a disposable chassis. To reduce weight, in one con?guration, the single use module s is formed from molded plastic such as polycarbonate, and the le use module chassis is 'formed ?om molded materials such as polycarbonate or carbon ?ber composites.

According to one e, the single use chassis unloaded with components weighs less than about 12 pounds and the loaded single use module Weighs less than about 18 pounds.

According to another feature, the multiple use housing and chassis unloaded with components weighs less than about 50 pounds, and when loaded with a multiple use module, batteries, gas, maintenance solutions, perfusion ?uid and a heart, weighs about 85 pounds or less. According to another advantage, the system of the invention including both single and multiple use modules, exclusive ofany perfusion, nutrient, preservative or other fluids, batteries and oxygen supply, weighs less than about 65 pounds.

The single use able chassis is sized and shaped for interlocking with the portable chassis ofthe multiple use module for electrical, mechanical, gas and fluid interoperation with the le use module. According to one feature, the multiple and single use s communicate with each other via an optical interface, which comes, into optical alignment automatically upon the single use disposable module being installed into the portable le use module. According to another feature, the portable multiple use module provides power to the single use disposable module via spring loaded connections, which also automatically connect upon the single use diSposable module being installed into the portable multiple use module. According to one feature, the optical interface and spring loaded connections ensure that connection between the single and multiple modules is not lost due to ng, for example, during transport over rough terrain.

In various embodiments, the organ chamber ly and the pump interface ly both mount to the able chassis. The pump ace assembly is aligned to receive a pumping force from the pump driver of the perfusion ?uid pump, and the interface assembly then translates the pumping force to the perfusion ?uid to circulate the perfusion ?uid to the organ chamber assembly. According to one embodiment, the perfusion ?uid pump is a pulsatile pump and the pump interface assembly includes a housing, a ?rst deformable ne, a ?uid inlet, and a fluid outlet. The housing ofthe pump interface assembly includes an interior side and an exterior side. The ?rst able membrane mounts in ?uid tight interconnection with the or side ofthe g to form a chamber between an interior side ofthe ?rst deformable membrane and the or side of the housing. The ?uid inlet receives per?lsion fluid, for example, from the reservoir, and provides the fluid into the chamber in response to the pump driver moving in a direction away from the interior side ofthe housing, and thus deforming the ?rst deformable membrane in the same direction. The outlet expels the perfusion fluid out of the chamber, for example, to the heater assembly, in response to the pump driver moving in a direction toward the interior side of the housing. ing to one con?guration, the pump interface assembly es a bracket for ?tting over a periphery of the ?rst deformable membrane to form the ?uid tight seal between the periphery ofthe interior side of the deformable membrane and a periphery of the interior side ofthe housing. According to a thither con?guration, the pump interface assembly includes a gasket for providing a ?uid tight seal between the perfusion ?uid pump driver and the pump interface housing.

According to one implementation, the system also includes a flow valve positioned on the input to the ?uid inlet. The ?ow valve includes a ball valve ly oriented to open and pass the perfusion ?uid into the r through the bidirectional ?uid inlet in response to the pump driver moving in the ion avvay from the interior side ofthe housing, and oriented to close and stop perfusion ?uid g back out of the chamber through the ?uid inlet in response to the pump driver moving in the direction toward the interior surface of the g. In a further implementation, the ?uid outlet also includes a ball valve assembly oriented to close in response to the pump driver moving in the direction away ?om the or surface ofthe housing, and to open to expel the organ perfusion fluid through the ?uid outlet in response to the pump driver moving in the direction toward the or side ofthe housing.

Optionally, the perfusion ?uid pump rigidly mounts to the portable multiple use chassis, the pump interface assembly rigidly mounts to the disposable single use chassis, and the system includes features for automatically forming a fluid tight seal between the perfusion pump driver and the pump interface assembly in response to the single use diaposable module being inter?tted with the portable multiple use module. More particularly, the pump interface assembly may include one or more tions out ofthe exterior side ofthe interface assembly housing, sized and shaped for engaging with and abutting one or more surfaces on the le le-use module to force/draw the or side of the pump interface assembly g in a direction toward the pump driver of the perfusion pump.

According to one feature, the pump interface assembly includes a second deformable membrane mounted adjacent to the ?rst deformable membrane for providing a fault tolerant seal in case the ?rst deformable membrane tears. According to another e, the pump ace assembly is formed at least in part from a polycarbonate or other molded plastic material, to reduce the weight of the single use disposable module.

In one embodiment, the perfusion ?uid oir mounts to the single use disposable chassis and is in ?uid communication with the organ chamber. According to a r embodiment, the flow mode selector valve mounts to the disposable chassis. In other embodiments, the solid state perfusion heater ofthe invention mounts to the disposable chassis. The oxygenator is preferably provided with the multiple-use module, but in certain embodiments may alternatively be part of the disposable module. The oxygen source feeding the oxygenator may be included on the le use portable s, may be part ofthe multiple~use module, or may be external to the .

In one con?guration, the various sensors associated with the heater assembly, the oxygenator and/or the perfusion fluid pump are included on the disposable single use module. However, this need not be the case, for example, with regard to non-perfusion fluid contacting sensors. According to one embodiment, the single use able module employs an oxygen sensor including iii-line cuvette through which the perfusion fluid passes, an optical source for directing light at the perfusion ?uid passing through the cuvette, and an optical sensor for measuring an optical quality of the perfusion ?uid passing through the cuvette. Preferably, the in~1ine cuvctte ssly or substantially seamlessly attaches to a per?rsion fluid ?ow conduit to reduce turbulence in the pei?ision fluid and provide one or more te ements. The seamless or substantially seamless con?guration also reduces damage to any blood based components ofthe perfusion ?uid.

According to a ?lrther con?guration, the disposable single—use module includes the above~mentioned plurality ofinline compliance chambers located, for example, at the outlet of the perfusion ?uid pump, and on either side of the mode select valve between the organ r and the mode select valve. In a timber embodiment, the disposable single- use module includes a plurality ofports for sampling fluids from the organ chamber assembly. According to one feature, the ports are interlocked such that sampling ?uid from a ?rst of the plurality ofports its simultaneously sampling ?uids from a second port of the plurality. This safety feature reduces the likelihood ofnrixing ?uid samples and inadvertently opening the ports. In one embodiment, the organ chamber assembly includes ports for ?uid interconnection with one or more ofthe pulmonary artery, aorta, and left atrium interfaces.

IO In another aspect, the invention is directed to a method ofpreserving a heart ex— vivo. The method includes placing a heart in a protective chamber of a portable organ care system, pumping a perfusion ?uid to the heart, the perfusion ?uid being at a temperature ofbetween about 25° C and about 37° C, and at a volume een about 200 ml/min and about 5 Umin, monitoring one or more physiologic characteristics ofthe heart while it is beating in the protective chamber, and adjusting a pumping characteristic based at least in part on the electrical characteristics to preserve the heart ex vivo.

According to another aspect, the invention is directed to a method endng a heart ex vivo, the method including the steps ofplacing a heart on one or more electrodes in a protective r ofa portable organ care system, pumping a perfusion fluid to the heart, the perfusion ?uid being at a ature ofbetween about 25° C and about 37° C, and at a volume of between about 200 ml/min and about 5 L/min, and-monitoring ical signals from the odes While pumping the perfusion ?uid to the heart to preserve the heart ex vivo.

In a further asPect, the invention is directed to a method oftransporting a heart ex vivo, including the steps ing a heart for transplantation in a protective chamber of a portable organ care system, pumping a perfusion ?uid into the heart via an aorta of the heart, providing a flow ofthe perfusion ?uid away ?'om the heart via a right ventricle of the heart, and orting the heart in the portable organ care system from a donor site to a recipient site while pumping the ion ?uid into the heart via the aorta and providing the flow of the perfusion ?uid away from the heart via the right ventricle.

According to an additional aspect, the invention is directed to a method of evaluating a heart for transplantation, ing the steps ofplacing a heart in a protective chamber of a portable organ care , pumping a perfusion fluid into the heart via a le? ventricle of the heart, providing a flow ofthe perfusion ?uid away from the heart via a right ventricle of the heart, transporting the heart via the portable organ care system from a donor site to a recipient site while pumping the per?ision ?uid into the heart via the left cle and providing the flow of the perfusion ?uid away from the heart via the right ventricle; prior to transPIanting the heart into a recipient, operating a ?ow control external to the protective r to alter a ?ow of the perfusion ?uid such that the perfusion ?uid is'pumped into the heart via a left atrium ofthe heart and is ?owed away from the heart via the right ventricle and the left ventricle of the heart; and performing an evaluation of the heart. In certain embodiments the evaluation includes performing an ELA test on the heart while the perfusion ?uid is pumping.

In another aspect, the invention is directed to a method iding therapy to a heart The method includes placing a heart in a tive chamber of a portable organ care system, pumping a perfusion fluid into the heart via a left ventricle of the heart, providing a ?ow of the perfusion fluid away from the heart via a right ventricle of the heart, operating a flow control external to the protective chamber to alter a ?ow ofthe ion ?uid such that the perfusion ?uid is pumped into the heart via a left atrium ofthe heart and is ?owed away from the heart via the right ventricle and the left ventricle of the heart, and administering a therapeutic treatment to the heart. The treatments may include, for example, stering one or more ofimmunosuppressive treatment, chemotherapy, gene therapy and irradiation therapy to the heart. ing to another aspect, the invention is directed to a method oftransplanting a heart. The method includes arresting a heart of a donor, explanting the heart from the donor, transferring the heart to an organ care system, and pumping a perfusion ?uid to the heart in less than 30 minutes after explanting the heart from the donor (so as to reduce the heart’s explantation cold ischemia time), the perfusion ?uid being at a temperature of between about 32° C and about 37° C. In certain ments the heart is brought to a temperature ofbetween about 35° C and about 37° C in less than 10 minutes a?er erring the heart to the organ care system.

These and other features and ages ofthe invention are described in further 3O detail below with regard to illustrative embodiments ofthe invention.

Brief Description of the Drawings The following ?gures depict illustrative embodiments of the invention in which like reference numerals refer to like ts. These ed embodiments may not be drawn to scale and are to be understood as illustrative of the invention and not as limiting, the scope of the invention instead being de?ned by the appended claims.

Figure l is a schematic diagram ofa portable organ care system according to an illustrative embodiment of the invention.

Figure 2 is a diagram depicting a harvested heart.

Figure 3 is a tual diagram depicting the harvested heart of Figure 2 interconnected with the organ care system ofFigure l in a normal ?ow mode ration according to an illustrative embodiment of the invention.

Figure 4 is a conceptual diagram depicting the harvested heart ofFigure 2 IO onnected with the organ care system ofFigure l in a retrograde ?ow mode con?guration according to an illustrative embodiment of the invention.

Figures 5A—5F show various views ofan organ chamber assembly of the type employed in the organ care system ofFigure 1 according to an illustrative embodiment of the invention.

Figures 6A-6F show various views of a perquion heater assembly of the type employed in the organ care system of Figure 1 according to an illustrative embodiment of the invention.

Figure 7 shows a more detailed View of an ary resistive heater element of the type employed in the heater assembly ofFigures 6A—6F.

Figures 8A-8C show various views of a perfusion fluid pump ace assembly according to an rative embodiment of the invention.

Figure 9 shows a perspective view ofa pump driver side of a perfusion ?uid pump assembly ofthe type depicted in Figure 1, along with a bracket for ng with the perfusion pump interface assembly.

Figure 10 shows a side View ofthe per?lsion fluid pump interface assembly of Figures SA-SC mated with the pump driver side ofthe perfusion ?uid pump ly of Figure 9.

Figure 11 depicts a block diagram of an illustrative control scheme for controlling operation of the organ care system of Figure 1.

Figure 12 is a block diagram of an exemplary data acquisition subsystem of the type that may be ed with an the illustrative organ care system of Figure 1.

Figure 13 is a block diagram ofan exemplary heating control subsystem of the type that may be employed for maintaining perfusion ?uid temperature in the illustrative organ care system ofFigure 1.

Figure 14 is a block diagram ofan exemplary power management subsystem ofthe type that may be employed in the rative organ care system of Figure 1.

Figure 15 is a block diagram of an ary pumping l subsystem ofthe type that may be employed for lling operation ofa perfusion ?uid pump assembly in IO the rative organ care system ofFigure 1.

Figure 16 is a graph depicting an r-wave with which the pumping control subsystem ofFigure 15 synchronizes according to an illustrative embodiment of the invention.

Figure 17A~17J depict exemplary display screens ofthe type that may be employed with an operator interface according to an illustrative ment ofthe invention.

Figures 18A and18B show an exemplary implementation of the system ofFigure 1 according to an illustrative embodiment of the invention.

Figures l9A-19C Show various views of the system ofFigures 18A and 1813 with its top off and front panel open according to an illustrative embodiment of the invention.

Figure 20A is a ?oat perspective view of the system of Figures 18A and 18B with the top removed, the front panel open and the single use disposable module removed according to an illustrative embodiment of the invention.

Figure 2013 is a side View of a slot formed in a basin ofthe multiple use module of Figure 20A for engaging with a corresponding projection in the single use di5posable module.

Figure 21A shows a mounting bracket for receiving and looking into place the single use disposable module within the multiple use module of Figure 20A.

Figures 21B and 210 show installation of the single use disposable module into the multiple uSe module using the mounting bracket ofFigure 21A according to an illustrative embodiment of the invention.

Figures 22A-22C show exemplary mechanisms for automatically making 6180110» optical interconnections between the single use disposable module and the multiple use module during the installation ofFigures 21B and 21C.

Figures 23A-ZSC show various views of the system of Figures {SA and 18B with all ofthe external walls removed according to an illustrative embodiment of the invention.

Figure 23D is a conceptual diagram showing interconnections between the t beans res 23A~23C according to an illus..ative embodiment ofthe invention. s 24A—24E show various top perspective views of a single use disposable module according to an illustrative embodiment of the invention.

IO Figures 25A-ZSC show various bottom persPective views of the illustrative single use diSposabie module ofFigures 24A-24D.

Figures 26A and 26B depict the operation of a flow mode selector valve according to an illustrative embodiment of the invention.

Figures 27A and 27B show s top views ofthe single use disposable module of Figures lQA-lQC with the top off of illustrative organ chamber.

Figures 28A » 280 show various views of an exemplary crit and oxygen saturation sensor of the type employed in the illustrative single use disposable module of Figures C.

Figure 29A is a ?ow diagram depicting a donor-side s for removing an organ from a donor and placing it into the organ care system ofFigure 1 according to an illustrative embodiment ofthe invention.

Figure 29B is a m depicting a ted heart with suture and cannulation sites according to an illustrative embodiment of the invention.

Figure 30 is a flow diagram depicting a recipient-side process for removing an organ from the organ care system ofFigure 1 and transplanting it into a recipient according to. an illustrative embodiment of the invention.

Figure 31 depicts a chart demonstrating olyte stability for an organ under going perfusion in forward mode ing to an embodiment of the ion.

Figure 32 depicts a chart demonstrating electrolyte stability for an organ under going perfusion in retrograde mode according to another an embodiment of the iHVention.

Figure 33 depicts a chart demonstrating the arterial blood gas pro?le for an organ under going perfusion according to an embodiment ofthe invention.

Illustrative Description As described above in summary, the invention generally provides improved approaches to ex-vivo organ care. More particularly, in s embodiments, the invention is directed to improved systems, methods and devices relating to ining an organ in an ex—vivo portable environment. According to one improvement, the organ preservation system of the invention maintains a heart beating at or near normal physiological ions. To this end, the system circulates an oxygenated, nutrient enriched perfusion fluid to the heart at nearphysiological ature, pressure and ?ow rate. According to one entation, the system employs a perfusion ?uid solution that more accurately mimics normal physiologic ions. In one embodiment, the perfusion ?uid is blood—product based. In ative embodiments, the solution is synthetic blood substitute based. In other embodiments the solution may contain a blood product in combination with a blood substitute product.

According to various illustrative embodiments, the improvements ofthe ion enable an organ, such as a heart, to be maintained ex~vivo for extended periods of time, for erample, exceeding 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 or more hours. Such extended ex-vivo maintenance times expand the pool ofpotential recipients for donor organs, making geographical distance between donors and recipients less important.

Extended ex—vivo maintenance times ofthe invention also provide the time needed for better genetic and HLA matching between donor organs and organ recipients, increasing the likelihood of a favorable outcome. The ability to maintain the organ in a near physiologic functioning condition also enables a clinician to evaluate the organ’s ?mction ex-vivo, further increasing the likelihood oftransplantation success. In some ces, the extended maintenance time enables l operators to perform repairs on donor organs with minor defects. ing to another advantage, the increased ex-vivo organ nance times of the ion enable an organ to be removed from a patient, treated in isolation o, and then put back into the body of a patient Such treatment may include, without limitation, surgical treatments, , bio~, gene and/or radiation therapies.

The illustrative systems, methods and devices of the invention are described below in the following order. First, the components of an illustrative organ care system 100 are described. Second, illustrative operation ofthe system 100 is discussed. Third, a subset of the components ofthe system 100 are described in further . Fourth, illustrative control s and methods for the system 100 are discussed. Fifth, an illustrative user interface is described. Sixth, mechanical es of the system 100 are discussed in further detail with regard to an exemplary implementation. Seventh, exemplary methods for employing the system 100 during an organ harvest, transport, and transplantation procedure are described. , illustrative perfusion, nutritional and preservative solutions suitable for use with the system 100 are presented. g to the illustrative embodiments, Figure 1 s a schematic diagram of a portable organ care system 100 according to an illustrative embodiment of the invention.

Figure 2 shows a conceptual drawing of a heart 102, which may be preserved/maintained ex-vivo by the organ care system 100 ofthe invention. Referring to Figures 1 and 2, the illustrative system 100 includes an organ chamber assembly 104 for containing the heart 102 during ex~vivo maintenance, a reservoir 160 for holding, defoaming and ng the perfusion ?uid 108, portal 774 for loading perfusion ?uid 108 into the reservoir 160 and a portal 762 for applying therapeutics to the ?uid 108 contained in the reservoir 160, a perfusion ?uid pump 106 for pumping/circulating perfusion ?uid 108 to and from the harvested heart 102; a heater assembly 110 for maintaining the temperature ofthe perfusion ?uid 108 at or near physiological temperatures; a ?ow mode selector valve 112 for switching between normal and retrograde aortic flow modes (also referred to as "normal ?ow mode" and "retrograde ?ow mode," tively); an oxygenator 114 for re- oxygenating the perfusion fluid 108 subsequent to it being eitpelled by the heart 102; a nutritional subsystem 115 for replenishing nutrients 116 in the perfusion ?uid 108 as they are metabolized by the heart 102 and for providing onal preservatives 118 to the ion ?uid to reduce, for example, ischemia and/or other re-perfusion related injuries to the heart 102. The illustrative system 100 also es a plurality of sensors, including without limitation: temperature sensors 120, 122 and 124; pressure sensors 126, 128, I30 and 132; perfusion ?ow rate sensors 134, 136 and 138; a perfusion fluid ation sensor 140; and sensor electrodes 142 and 144, and de?brillation source 143. The system 100 ?irther includes: s components employed for maintaining suitable ?ow conditions to and from the heart 102; an operator interface 146 for assisting an Operator in monitoring operation of the system 100, and the condition of the heart 102, and for enabling the operator to select various operating parameters; a power subsystem 148 for providing fault tolerant power to the system 100; and a controller 150 for controlling operation of the organ care system 100. ing also to Figures 3 and 4, according to the illustrative embodiment, the system 100 can in the heart 102 in two modes of operation ~- a normal ?ow mode, shown in Figure 3, and a rade ?ow mode shown in Figure 4. Generally, in the normal ?ow mode ofFigure 3, the system 100 circulates the perfusion ?uid 108 to the heart 102 in the same manner as blood would circulate in the human body. More particularly, referring to Figures 1—3, the ion ?uid enters the left atrium 152 ofthe heart 102 via the puhnonary vein 168. The per?rsion ?uid 108 is flowed away from the right ventricle 154 via the ary artery 164 and away from the led 156 ventricle via the aorta 158. In normal ?ow mode, the system 100 pumps the per?ision ?uid to the heart 102 at a near physiological rate ofbetween about 1 nun and about 5 liters/minute.

This mode is useful, for e, for performing functional testing to verify that the heart 102 is defect free, both prior and subsequent to transportation to a donor location.

Alternatively, in retrograde flow mode, shown in Figure 4, the system 100 ?ows the perfusion ?uid 108 into the heart 102 via the ao?a 158, through the coronary sinus 155 and other coronary vasculature ofthe heart, and out ofthe right ventricle 154 of the heart 102 via the pulmonary artery 164. As discussed in further detail below with regard to Figures 24A and 2413, the system 100 also provides a trickle ?ow 769 to the left atrium 152 through trickle valve 768. The trickle ?ow is provided in an amount suf?cient to moisten the left atrium 152 and left ventricle 156. In certain applications the trickle flow is less than about 5 ml/min, less than about 1 ml/min, or less than about 0.1 mI/min. In this mode of Operation, the system 100 reduces the ?ow rate of the ion ?uid 108 to between about 300 milliliters/minute and about 1 liter/minute. The inventors have found that the retrograde ?ow path ofFigure 4, along with the reduced ?ow rate, reduces damage to the heart 102 during extended periods of ex-vivo maintenance. Thus, according to one feature of the invention, the heart 102 is transported to a donor site in retrograde ?ow mode.

Having brie?y described the normal and retrograde ?ow modes, the system 100 will next be described in ?irther detail operationally. Referring once again to s 1—4, in one practice, the heart 102 is harvested from a donor and cannulated into the organ chamber assembly 104. The perfusion ?uid 108 is prepared for use within system 100 by being loaded into the reservoir 160 via portal 774 and, optionally, being treated with therapeutics via portal 762. The pump 106 pumps the loaded perfusion ?uid 108 from a oir 160 to the heater assembly 110. The heater assembly 110 heats the per?ision ?uid 108 to or near a normal physiological temperature. According to one ment, the heater assembly 110 heats the perfusion ?uid to between about 32° C and about 37° C.

The heater assembly 110 has an internal ?ow channel with a cross-sectional ?ow area that is approximately equal to the inside cross—sectional area of?uid conduits that carry the ion ?uid l08 into and/or away from the heater assembly 110, so as to ze disturbance of ?uid ?ow. From the heater ly 110, the perfusion ?uid 108 ?ows to the ?ow mode selector valve 1 l2.

Initially, the flow mode selector valve 112 is positioned in retrograde mode to direct the perfusion ?uid 108 from the heater assembly 110 into the organ chamber assembly 104 via a ?rst interface 162. Also referred to as an aorta interface or left ventricle ace, the interface 162 includes cannulation to vascular tissue of the le? ventricle Via an aperture 228b located on the organ chamber assembly 104 (as shown in Figures 5A - 5B). As the heart 102 warms, it begins to beat which causes the heart 102 to pump the perfusion fluid 108 through the coronary vasculature 155 and out of the heart 102 through the right ventricle 154 via a second ace 166. The second interface 166, also referred to as a pulmonary artery interface or a right ventricle interface, includes cannulation to vascular tissue ofthe right ventricle via an re 2280 located on the organ chamber assembly 104 (as shown in Figures 5A~ SB). As mentioned above, in retrograde ?ow mode, ?uid is not actively pumped into or out of the left side of the heart, except for a relatively small trickle 769 ofperfusion fluid, which is delivered to moisten the left atrium 152 and left ventricle 156, as described below in reference to Figures 24A —- In response to the flow mode selector valve 112 being placed in the normal mode position, it directs the perfusion ?uid 108 into the left atrium 152 ofthe heart 102 via a third interface 170. The third interface 170, also referred to as a pulmonary vein ace or left atrium interface, es cannulation to ar tissue ofthe left atrium 152 via an aperture 228a located on the organ chamber assembly 104 (as shown in Figures 5A - SB).

The heart 102 then expels the perfusion ?uid 108 through the left ventricle 156 via the aorta interface 162 and through the right ventricle 154 via the pulmonary artery ace Each of the interfaces 162, 166 and 170 may be cannulated to the heart 102 by pulling vascular tissue (e.g., an aorta stub) over the end ofthe interface, then tying or otherwise securing the tissue to the interface. The vascular tissue is preferably a short segment ofa blood vessel (e.g., an aorta stub 158) that remains connected to the heart 102 after the heart 102 is severed and explanted from the donor. For example, the aorta interface 162 is cannulated to a small segment of the severed aorta 158 which has been termed by severing the aorta 158 in a location down-stream from the ry sinus 155.

In certain applications, the short vessel segments maybe about 5 to about 10 inches in length or . The segments may also be shorter than about 5 inches. The segments in other may be about 2 to about 4 inches in length, or about 1 to about 2 inches in length; ations the segments may be less than about V2 inch, or less than about 1/4 inch.

Alternatively, the cannulation may occur by af?xing the interface directly to the able atrium or ventricle, as may be preferred in applications where the heart 102 is prepared for explantatlon by severing an entire blood vessel Without leaving any stub portion of the vessel connected to the heart 102. For example, a hit atrium 152 cannulation can be formed by inserting the interface 170 directly into the left atrium 152 and clamping the interface 170 in place, Without the need to tie to any pulmonary vein 168 tissue.

With continued reference to Figure 1, in both ?ow modes the perfusion ?uid 108 flows from the pulmonary artery interface 166 into the oxygenatcr 114. The oxygenator 114 receives gas from an external or onboard source 172 h a gas regulator 174 and a valve that controls gas flow chamber 176, which can be a pulse—width modulated solenoid flow rate. A gas ?ow, or any other gas control device that allows for precise control of gas 172 is. The gas pressure gauge 178 provides a visual indication ofhow full the gas supply transducer 132 provides r information to the controller 150. The ller 150 can regulate tically the gas ?ow into the oxygenator 114 in dependence, for example, on the perfusion ?uid oxygen content measured at the sensor 140. According to various rative embodiments, the oxygenator 114 is a standard membrane oxygenator, such as the Liliput 2 manufactured by Dideco, a division of Sorin ical, or the MINE/[AX PLUSTM ctured by Mcdtronic, Inc. In the illustrative embodiment, the gas includes an oxygen and carbon dioxide mixture. An exemplary composition of such a mixture contains about 85% 02, about 1% 002, with the balance being N2. Subsequent to re- oxygenation, the oxygenator 114 returns the perfusion fluid 108 to the reservoir 160.

According to the illustrative embodiment, the sensor 140 measures the amount of light absorbed or re?ected by the perfusion ?uid 108 when applied at a multi-wavelength to provide an optical-based ement of oxygen saturation. Since the perfusion ?uid 108 is blood product based in certain embodiments, it may n red blood cells (i.e., oxygen carrying cells). Accordingly, the sensor 140 also es a signal 145 indicative of a hematocrit measurement of the ion ?uid 108. In alternative embodiments the solution 108 is formed ofa synthetic blood substitute, while in other embodiments, the solution 108 may contain a blood t in combination with a blood substitute product.

Also, in both flow modes, the nutritional tem 115, ing a supply of maintenance solutions 116/118 and an infhsion pump 182, infuses the perfusion ?uid 108 with nts 116, such as glucose, as the perfusion 108 solution ?ows h the system 100, and in some embodiments, while it is in the reservoir 160. The maintenance solutions 116/1 18 also include a supply oftherapeutics and preservatives 118 for reducing ischemia and other re-perfusion related injuries to the heart 102.

Both nonnal and retrograde ?ow modes are described in ?u'ther detail below with reference to Figures 24A—2613. ~ According to the illustrative embodiment, the system 100 is primed prior to introducing an organ into the organ chamber assembly 104. During priming, a priming solution (described below) is inserted into the organ chamber 160 and pumped through the system 100. In one exemplar application, the priming occurs for a period ofbetween about and about 20 minutes. The cannulation interfaces 162, 166 and 170 in the organ chamber assembly 104 are bypassed to enable normal mode ?ow ofperfusion fluid 108 through the system 100, without the donor heart 102 being present. Blood (or a synthetic blood substitute) is then loaded into the reservoir 160. The may be the blood exsanguinated from the donor during harvesting of the heart 102 or obtained from typed and cross~matched banked blood. The system 100 then ates the blood (or blood substitute) through the system 100 to heat, oxygenate, and ?lter it. Nutrients, preservatives and/or other therapeutics are provided via the infusion pump 1 82 ofthe nutritional subsystem 115. Various parameters may also be lized and calibrated via the operator interface 146 during priming. Once the system 100 is running appropriately, the pump rate can be decreased or brought to zero, and the heart 102 can be cannulated into the organ chamber assembly 104‘ The pump rate can then be increased. Priming ofthe system 100 is described in ?rr?ler detail below with reference to the ?ow diagram of Figure 29A.

As shown in Figure l, the system 100 also includes a plurality of compliance chambers 184, 186 and 188. The compliance chambers 184, 186 and 188 are essentially small inline ?uid accumulators with ?exible, resilient walls designed to simulate the human body’s vascular compliance by aiding the system in more accurately mimicking blood ?ow in the human body, for e, by providing ?ow ressure and/or by ?ltering/reducing ?uid pressure Spikes due, for example, to ?ow rate changes and/or the pumping of the pump 106. According to the illustrative embodiment, the compliance chamber 184 is located between an output 112a of the mode valve 112 and the oir 160 and operates in combination with an adjustable clamp 190 during normal ?ow mode to provide back re to the aorta 158 to cause per?lsion ?uid to ?ow into the ry sinus 155 to feed the heart 102. In the illustrative embodiment, the fluid back-pressure provided to the aorta 153 is n about 55 mmHg and about 85 mmHg, which is within an acceptable hysiologic range ofmean aortic blood pressure (which is typically between about 80 mmHg and about 100 mmHg). The back pressure to the aorta 158 aids the system 100 in simulating normal physiologic conditions. The compliance chamber 186 is located between an output 112b of the mode valve 112 and the pulmonary vein cannulation interface 170 ofthe organ chamber ly 104. The primary function of the compliance r 186 is to provide ressure to the left atrium 152 and to smooth re/?ow spikes caused ?rom the pumping action of the perfusion ?uid pump 106, which delivers blood to the heart without causing substantial ?uid pressure spikes. In the illustrative embodiment, the ?uid back-pressure provided to the left auium 152 is between about 0 urinal-lg to about 14 man, which is approximately the same as the left atrial re under normal physiologic conditions. . The compliance chamber 188 is located between an output of a one way valve 310 and an inlet 110a ofthe heater 110. The primary function of the compliance chamber 188 is also to smooth pressure/flow spikes caused by the pumping action ofthe perfusion ?uid pump 106 and to provide ?uid back— pressure to the pulmonary artery 164. In the illustrative embodiment, the fluid back- 3O pressure provided to the pulmonary artery 164 is between about 0 mmElg and about 25 mmHg, which is within an acceptable nearuphysiologic range ofmean arterial blood pressure (between about 0 1111an and about 12 mmHg).

The compliance chambers 184, 186 and 188 provide the bene?ts described above through their size and shape and the materials used in their design. The chambers 184, 186 and 188 are sized to contain about 20 ml to about 100 ml of ?uid 108, and they are shaped in an oval con?guration to allow them to receive ?uid 108 and expand to dampen pressure spikes and to provide ressure to the heart 102. In certain applications, the material used for the chambers 184, 186 and 188 includes at least one ?exible membrane, selected so‘ that the chambers have a Shore A durametn'c hardness (ASTM D2240 00) of about 10 (more ?exible) to about 60 (less ?exible), with certain preferred embodiments having a hardness of between about 30 (+/— about 8) and about 50 (+/- about 8). In the illustrative embodiment, the ance chamber 184 has a Shore A hardness of about 50 (+/- about 8) and the compliance chamber 186 has a Shore A hardness of about 30 (+/- about 8). In the rative embodiment, the compliance chamber 188 has a dual-layered con?guration, with an inner chamber having a Shore A hardness t 50 (+/- about 8) and an outer sleeve having a Shore A hardness ofabout 30 (+/- about 8). Alternatively, the inner chamber can have a lower hardness (e.g., about 30, +/— about 8) and outer sleeve can have a higher hardness (cg, about 50, +/— about 8)).

Having provided an operational overview ofthe system 100, the organ chamber assembly 104, the perfusion heater assembly 110, and a pump head interface assembly 192 for interfacing with the pump 106 are next described in further detail. Figures SA—SF depict various views of the illustrative organ r assembly 104 ofFigure 1. As shown most clearly in Figures SA-SD, the organ chamber assembly 104 includes a g 194, a outer lid 196 and an intermediate lid 198. The housing includes a bottom 1946 and one or more walls 194a—194d for containing the heart 102. The ediate lid 198 covers an g 200 to the housing 194 for substantially enclosing the heart 102 within the housing 194. As most clearly shown in Figures 5E and SF, the ediate lid 198 includes a frame 1988 and a ?exible ne 198b suspended within the frame 198a.

The ?exible membrane 198b, ably, is transparent but may be opaque, translucent, or substantially transparent. According to one feature, the ?exible membrane includes suf?cient excess membrane material to contact the heart 102 when contained within the housing 195. This feature enables a medical or to touch/examine the heart 102 indirectly through the membrane 198b, or apply an ultrasound probe to the heart 102 through the membrane 198b, while maintaining sterility ofthe housing 195. The membrane 198b may be made, for example, from any suitable flexible polymer plastic, for example ethane. The ne 19% may also have integrated elastically conductive pads/contacts 1993 and 19% through which electrical activity of the heart may be sensed via electrodes such as the electrodes 142 and 144, and/or for through which de?brillation or pacing signals may be delivered, as described more ?llly below.

Alternatively, the contacts 199a and 1991) may be electrodes including all or a portion of the functionality of the electrodes 142 and 144. As shown in Figure SC, the outer lid 196 Opens and closes over the intermediate lid 198 independently from the intermediate lid 198. Preferably, the outer lid 196 is rigid enough to protect the heart 102 from physical t, indirect or indirect. The outer lid 196 and the chamber 194 may also he made ?om any suitable r plastic, for example polycarbonate.

According to one entation, the housing 194 includes two hinge sections 202a and 202b, and the intermediate lid frame 198a includes two corresponding mating hinge sections 204a and 204b, respectively. The hinge sections 202a and 202b on the housing 194 inter?t with the hinge sections 204a and 204b on the intermediate lid ?ame 198a to enable the intermediate lid 198 to open and close relative to the opening 200 ofthe housing 194. As shown most clearly in Figures 5D and SF, the organ chamber ly 104 also includes two s 206a and 206?) for securing the intermediate lid 198 closed over the opening 200. As shown in Figures 513 and SF, the s 206a and 2061) rotatably snap fit onto latch hinge section 2083 and 208b, respectively, on the wall 194:: ofthe 2O housing 194. As shown most clearly in Figures 5A and 513, the intermediate lid frame 198a also includes a hinge section 210. The hinge section 210 rotatably snap ?ts with a mating hinge section 212 on the outer lid 196 to enable the outer lid 196 to open without opening the intermediate lid 198. As shown best in Figures SB, 5D and SF, the outer lid 196 also includes two cutouts 214a and 21413 for enabling the latches 206a and 206b to clamp down on the edge 216 ofthe intermediate lid ?ame 1983. As shown in Figures 5B, 5D and SF, the organ r assembly 104 also includes a latch 218, which rotatably snap ?ts onto a hinge part 220 on the wall 194:; ofthe housing 194. In operation, the latch 218 engages a tab 221 on the edge 225 of the outer lid 196 to secure the outer lid 196 closed over the intennediate lid 198.

As shown most clearly in Figures 5E and SF, the intermediate lid also includes two gaskets 1980 and 198d. The gasket 198d inter?ts n a periphery of the ediate lid frame 198a and a periphery of the outer lid 196 to form a ?uid seal between the intermediate lid 198 and the outer lid 196 when the outer lid 196 is closed. The gasket 198c inter?ts between an outer rim 194i" ofthe housing 194 and the intermediate lid frame 1983 to form a fluid seal between the intermediate lid 198 and the ery 194f of the housing 194 when the intermediate lid 198 is closed.

Optionally, the organ chamber assembly 104 includes a pad 222 or a sac assembly sized and shaped for inter?tting over an inner bottom surface 194g of the housing 194.

Preferably, the pad 222 is formed from a material resilient enough to cushion the heart 102 from mechanical vibrations and shocks during transport, for example a closed-cell foam.

According to one feature, the pad 222 es a mechanism for ably oning a pair of electrodes, such as the electrodes 142 and 144 ofFigure 1. According to the IO illustrative embodiment, the mechanism includes two throug11~apertures 224a and 2241) for passing electrical leads from the under side of the pad 222 to corresponding electrodes 142 and 144 on the heart—contacting e of the pad. ?assing the electrical leads through the pad 222 to the electrodes 142 and 144 enables the electrodes 142 and 144 to be ably positioned within the pad 222 to odate variously sized hearts. In other embodiments, the mechanism may include, without limitation, one or more differently oriented slots, indentations, protrusions, through apertures, partially h apertures, hooks, eyelets, ve patches, or the like. In certain embodiments, the pad 222 may be con?gured With one or more sleeve-like structures that allow an electrode to be inserted within the pad 222, thus providing a membrane-like surface ofthe pad 222 positioned n the electrode and the heart 102.

In some illustrative embodiments, the pad 222 is con?gured as a pad assembly, with the assembly including one or more electrodes, such as the electrodes 142 and 144, adjustably located in or on the pad 222. According to one advantage, the pad/electrode con?guration of the invention facilitates contact between the electrodes and the heart 102 placed on the pad 222, t temporarily or permanently suturing or otherwise mechanically connecting the electrodes to the heart 102. The weight of the heart 102 itself can also help stabilize the electrodes during tranSport. According to the illustrative ment, the odes 142 and 144 include one or more sensors for monitoring one or more electrical signals from the heart and/or de?brillators for providing an electrical signal to the heart. ‘As shown in Figures 1 and 5C, the organ chamber assembly 104 includes electrical interface connections 235343513, which mount into the apertures 234a~ 234b, respectively, in the wall 194b of the housing 194. A cover 226 is provided for protecting the ical interface connections 235a~23 5b when not being used.

As described below in further detail with reference to Figure 15, the interface connections 235a and 235b couple electrical signals, such as ECG signals, from the electrodes 142 and 144 out ofthe housing 194, for example, to the controller 194 and/or the operator ace 146. As described in further detail below with reference to Figure 22A, the ace connections 23 5a and 2351) may also couple to a de?brillation source, which may be either ed by external instrumentation or through circuitry within the system 100, and which can send a de?brillation or pacing signal 143 through odes 142 and 144 to the heart 102.

As shown most clearly in s 513 and SF, the organ chamber assembly 104 includes a resealable membrane ace 230, which mounts in an interface aperture 232.

The ace 230 includes a frame 230a and a resealable polymer membrane 230b mounted in the ?ame 230a. The membrane 230b may be made of silicone or any other le polymer. In Operation, the interface 230 is used to provide pacing leads, when necessary, to the heart 102, without having to open the chamber lids 196 and 193. The membrane 2301) seals around the pacing leads to maintain a closed nment around the heart 102. The membrane 23013 also reseals in response to ng the pacing leads.

As shown in Figures 5A and 5B, the organ chamber assembly 104 includes apertures 228a~228c for receiving the aorta interface 162, the pulmonary artery ace 166 and the pulmonary vein interface 170, described above with reference to Figures 1-4, 2O and below with reference to Figures 24A—2SC. As shown in Figure 5D, the organ chamber assembly 104 also includes a drain 201 for draining ion ?uid 108 out of the housing 194 back into the reservoir 160, and mounting receptacles 203A~203d for mounting the organ chamber assembly 104 onto the single use module (shown at 634 in Figure 19A).

Figures 6A-6F depict various views ofthe per?rsion ?uid heater assembly 110 of Figure 1. As shown in Figures 6A and 6B, the heater assembly 110 includes a housing 234 having an inlet 110a and an outlet 11%. As shown in both the longitudinal cross-sectional View ofFigure 6D and the lateral cross-sectional View ofFigure 6B, the heater assembly 110 includes a ?ow channel 240 extending between the inlet 110a and the outlet 110b.

The heater assembly 110 may be conceptualized as having upper 236 and lower 238 symmetrical halves. Accordingly, only the upper half is 3110an in an exploded View in Figure 6F.

Referring now to Figures 6D~6F, the ?ow channel 240 is formed between ?rst 242 and second 244 flow channel plates. The inlet 110a ?ows the perfusion ?uid into the ?ow channel 240 and the outlet llOb flows the ion ?uid out ofthe heater 110. The ?rst 242 and second 244 flow channel plates have substantially bioinert per?ision ?uid 108 contacting surfaces (which may contain a blood-product in certain ments) for providing direct contact With the perfusion ?uid ?owing through the channel 240. The ?uid contacting surfaces may be formed from a treaunent or coating on the plate or may be the plate surface itself. The heater assembly 110 includes ?rst and second electric heaters 246 and 248, tively. The ?rst heater 246 is located nt to and couples heat to a ?rst heater plate 250. The ?rst heater plate 250, in turn, couples the heat to the ?rst ?ow channel plate 242. Similarly, the second heater 248 is located adjacent to and couples heat to a second heater plate 252. The second heater plate 252 couples the heat to the second ?ow channel plate 244. According to the illustrative embodiment, the ?rst 250 and second 252 heater plates are formed ?om a material, such as aluminum, that conducts and distributes heat from the ?rst 246 and second 248 electric heaters, respectively, relatively uniformly. The uniform heat distribution of the heater plates 250 and 252 enables the ?ow channel plates to be formed from a bioinert material, such as titanium, reducing concern regarding its heat distribution characteristic.

Referring particularly to Figures 6E and 6F, the heater assembly 110 also es O~rings 254 and 256 for ?uid sealing respective ?ow channel plates 242 and 244 to the g 234 to form the flow channel 240.

The heater assembly 110 further includes ?rst assembly brackets 258 and 260. The ly bracket 258 mounts on the top side 236 ofthe heater assembly I 10 over a periphery of the electric heater 246 to sandwich the heater 246, the heater plate 250 and the flow channel plate 242 between the assembly bracket 258 and the g 234. The bolts 262a-262j ?t through corresponding through holes in the bracket 258, electric heater 246, heater plate 250 and flow channel plate 242, and thread into corresponding nuts 64j to af?x all of those components to the housing 234. The assembly bracket 260 mounts on the bottom side 238 ofthe heater assembly 110 in a similar fashion to af?x the heater 248, the heater plate 252 and the ?ow l plate 244 to the housing 234. A resilient pad 268 inter?ts within a periphery of the bracket 258. Similarly, a resilient pad 270 inter?ts within a periphery of the bracket 260. A bracket 272 ?ts over the pad 268. The bolts 278a—278f inter?t through the holes 276a-276f, respectively, in the t 272 and thread into the nuts 2803—230fto compress the resilient pad 268 against the heater 246 to provide a more ef?cient heat transfer to the heater plate 250. The resilient pad 270 is compressed t the heater 24s in a similar fashion by the bracket 274.

As mentioned with t to Figure l, and as also shown in Figure 6A, the illustrative heater assembly 110 includes temperature sensors 120 and 122 and dual-sensor 124. The dual sensor 124 in ce includes a dual thermistor sensor for providing fault tolerance, measures the temperature ofthe perfusion fluid 108 exiting the heater assembly 110, and es these temperatures to the controller 150. As described in ?irther detail below with respect to the heating subsystem 149 ofFigure 13, the signals from the sensors 120, 122 and 124 may be employed in a feedback loop to control drive signals to the ?rst 246 and/or second 248 s to control the temperature of the heaters 256 and 248.

Additionally, to ensure that heater plates 250 and 252 and, therefore, the blood contacting surfaces 242 and 244 ofthe heater plates 250 and 252 do not reach a temperature that might damage the perfusion ?uid, the illustrative heater assembly 1 10 also includes temperature sensors/lead wires 120 and 122 for monitoring the temperature of the heaters 246 and 248, respectively, and providing these temperatures to the controller 150. In practice, the sensors ed to sensors/lead wires 120 and 122 are RTD (resistance temperature device) based. As also discussed in thither detail with respect to Figure 13, the signals from the sensors attached to sensors/lead wires 120 and 122 may be ed in a feedback loop to further control the drive signals to the ?rst 246 and/or second 248 heaters to limit the maximum temperature ofthe heater plates 250 and 252. As a fault protection, there are sensors for each of the heaters 246 and 248, so that if one should fail, the system can continue to operate with the temperature at the other sensor.

As described in further detail below with respect to Figure 13, the heater 246 of the heater assembly 110 receives ?om the controller 150 drive signals 281a and 281b (collectively 281) onto ponding drive lead 282a. Similarly, the heater 248 receives from the ller 150 drive signals 283a and 28% (collectively 283) onto drive lead 282b. The drive signals 281 and 283 control the current to, and thus the heat generated by, the respective heaters 246 and 248. More particularly, as shown in Figure 7, the drive leads 282a includes a high and a low pair, which connect across a resistive element 286 of the heater 246- The greater the current provided through the resistive t 286, the hotter the resistive element 286 gets. The heater 248 operates in the same fashion with regard to the drive lead 28%. ing to the illustrative embodiments, the element 286 has a resistance of about 5 ohms. However, in other illustrative embodiments, the element may have a resistance of between about 3 ohms and about 10 ohms. As discussed in more detail below with regard to Figures 11 and 13, the heaters 246 and 248 may be controlled independently by the processor 150.

According to the illustrative embodiment, the heater assembly 110 housing components are formed from a molded plastic, for example, polycarbonate, and weighs less than about one pound. More particularly, the housing 234 and the brackets 258, 260, 272 and 274 are all formed from a molded plastic, for example, polycarbonate. According to another feature, the heater assembly is a single use disposable assembly.

In operation, the illustrative heater assembly 110 uses between about 1 Watt and about 200 Watts ofpcwer, and is sized and shaped to transition perfusion ?uid 108 ?owing through the channel 240 at a rate of between about 300 ml/min and about 5 L/min from a temperature of less than about 30°C to a temperature of at least about 37°C in less than about 30 minutes, less than about 25 minutes, less than about 20 minutes, less than about 15 s or even less than about 10 minutes, Without substantially causing hemolysis of cells, or denaturing ns or otherwise ng any blood product portions of the perfusion ?uid.

According to one feature, the heater assembly 110 includes housing components, such as the housing 234 and the brackets 258, 260, 272 and 274, that are formed from a polycarbonate and weighs less than about 5 1b. In other ments, the heater assembly may weigh less than about 4 lb, less than about 3 lb, less than about 2 lb, or even less than about 1 lb. In the illustrative embodiment, the heater assembly 110 has a length 288 of about 6.6 inches, not including the inlet 110a and outlet 11013 ports, and a width 290 of about 2.7 inches. The heater assembly l 10 has a height 292 of about 2.6 inches. The flow channel 240 of the heater assembly 110 has a nominal width 296 of about 1.5 , a l length 294 of about 3.5 inches, and a l height 298 of about 0.070 inches.

The height 298 and width 296 are selected to provide for m heating ofthe perfusion ?uid 108 as it passes h the channel 240. The height 298 and width 296 are also selected to provide a sectional area within the channel 240 that is approximately equal to the inside cross—sectional area of ?uid conduits that carry the per?ision ?uid 108 into and/or away from the heater assembly 110. In one con?guration, the height 298 and width 296 are selected to provide a cross-sectional area within the channel 240 that is approydmately equal to the inside cross-sectional area ofthe inlet fluid conduit 792 (shown .32.. below with reference to Figure 25C) and/or substantially equal to the inside cross-sectional area of the outlet fluid conduit 794 (showu below. with reference to Figure 24E).

Projections 257a ~257d and 259a—259d are included in the heater ly 110 and are used to receive a heat-activated adhesive for binding the heating assembly to the multiple-use unit 650 (referenced in Figure 20A).

Figures EBA-80 show various views of a pump interface assembly 300 according to an illustrative embodiment of the invention. Figure 9 shows a perspective View of a pump- driver end ofthe ion ?uid pump assembly 106 ofFigure l, and Figure 10 shows the pump interface ly 300 mated with the pump-driver end ofthe perfusion ?uid pump assembly 106, according to an illustrative embodiment of the invention. Referring to Figures 8A-10, the pump ace assembly 300 includes a housing 302 having an outer side 304 and an inner side 306. The interface assembly 300 includes an inlet 308 and an outlet 310. As shown most y in the bottom View ofFigure SB and the exploded view of Figure BC, the pump interface assembly 300 also includes inner 312 and outer 314 O ring seals, two deformable membranes 316 and 318, a doughnut-shaped bracket 320, and half-rings 319a and 31% that ?t between the o-ring 314 and the bracket 320. The half- rings 319a and 31% may be made offoam, plastic, or other suitable material.

The inner O-ring 312 ?ts into an annular track along a periphery ofthe inner side 306. The ?rst deformable ne 316 mounts over the inner O-ring 312 in ?uid tight interconnection with the inner side 306 ofthe housing 302 to form a chamber between an interior side ofthe ?rst deformable membrane 316 and the inner side 306 of the housing 302. A second deformable membrane 318 ?ts on top of the ?rst deformable ne 316 to provide fault tolerance in the event that the ?rst deformable membrane 316 rips or tears. Illustratively, the deformable membranes 316 and 318 are formed from a thin polyurethane ?lm (about 0.002 inches thick). However, any suitable material of any suitable ess may be employed. Referring to Figures 8A and 8B, the bracket 320 mounts over the second deformable membrane 318 and the rings 319a and 31913 and af?xes to the housing 302 along a periphery of the inner side 306. Threaded fasteners 3223-322i attach the bracket 320 to the housing 302 by way ective ed apertures 324a-324i in the bracket 320. As shown in Figure 8B, the outer O-ring 314 inter?ts into an annular groove in the t 320 for providing ?uid tight seal with the. pump assembly 106. Prior to inserting O—ring 314 into the annular groove in bracket 320, the half-rings 319a and 31% are placed in the . The O-Iing 314 is then compressed and positioned within the annular groove in bracket 320. After being positioned within the annular groove, the O-ring 314 expands within the groove to seCure itself and the half— rings 319a and 31% in place.

The pump interface assembly 300 also includes heat stake points 32la—321c, which project hem its outer side 304. As described in further detail below with nce to s 21A~21C and 2411-240, the points 321a~3210 receive a hot glue to heat-stake the pump interface assembly 300 to a C—shaped bracket 656 of the single use disposable module s 635.

As shown in Figure 80, the ?uid outlet 310 includes an outlet g 310a, an outlet ?tting 310b, a ?ow regulator ball 31 00 and an outlet port 310d. The ball 3100 is sized to ?t within the outlet port 310d but not to pass through an inner aperture 326 of the outlet 310. The ?tting 310b is bonded to the outlet port 310d (e.g., via epoxy or another adhesive) to capture the ball 3100 between the inner aperture 326 and the ?tting 31%. The outlet housing 31011 is similarly bonded onto the ?tting 31%.

In operation, the pump interface assembly 300 is aligned to receive a pumping force from a pump driver 334 of the perfusion fluid pump ly 106 and translate the pumping force to the perfusion ?uid 108, thereby circulating the perfusion ?uid 108 to the organ chamber assembly 104. According to the rative embodiment, the perfusion ?uid pump assembly 106 includes a pulsatile pump having a driver 334 (described in further detail below with regard to Figure 9), which contacts the membrane 318. The fluid inlet 308 draws perfusion ?uid 108, for example, from the reservoir 160, and provides the ?uid into the chamber formed between the inner membrane 316 and the inner side 306 of the housing 302 in response to the pump driver moving in a direction away from the deformable membranes 316 and 318, thus deforming the nes 316 and 318 in the same direction. As the pump driver moves away from the deformable membranes 316 and 318, the pressure head of the ?uid 108 inside the reservoir 160 causes the perfusion ?uid 108 to flow from the reservoir 160 into the pump assembly 106. In this respect, the pump assembly 106, the inlet valve 191 and the reservoir 160 are oriented to provide a gravity feed ofperfusion ?uid 108 into the pump assembly 106. At the same time, the ?ow regulator ball 3100 is drawn into the aperture 326 to prevent perfusion ?uid 108 from also being drawn into the chamber h the outlet 310. It should be noted that the outlet valve 310 and the inlet valve 191 are one way valves in the rated embodiment, but in alternative embodiments the valves 310 and/or 191 are two-way valves. In response to the pump driver 334 moving in a direction toward the deformable membranes 316 and 318, the ?ow regulator ball 310s moves toward the ?tting 31% to open the inner aperture 326, which enables the outlet 310 to expel perfusion ?uid 108 out of the chamber formed between the inner side 306 of the housing 302 and the inner side of the defonnable membrane 316. A separate one-way inlet valve 191, shown between the reservoir 160 and the inlet 308 in Figure 1, stops any perfusion ?uid from being expelled out of the inlet 308 and ?owing back into the reservoir 160.

As discussed in ?n‘ther detail below with respect to Figures 18A—27B, in certain ments the organ care system 100 ically divides into a able single—use unit (shown at 634 in Figures l9A—19C and 24A~25C) and a non~disposable multi-use unit (shown at 650 in Figure 20A). In such embodiments, the pump assembly 106 rigidly mounts to the multiple use module 650, and the pump interface assembly 300 y mounts to the disposable single use module 634. The pump assembly 106 and the pump interface assembly 300 have corresponding interlocking connections, which mate together to form a fluid tight seal between the two assemblies 106 and 300.

More particularly, as shown in the perspective view ofFigure 9, the perfusion ?uid pump ly 106 includes a pump driver housing 338 having a top surface 340, and a pump driver 334 housed within a cylinder 336 ofthe housing 338 The pump driver housing 338 also includes a docking port 342, which includes a slot 332 sized and shaped for mating with a ?ange 328 projecting from the pump interface assembly 300. As shown in- Figure 10, the top surface 340 of the pump driver housing 338 mounts to a bracket 346 on the sposable le use module unit 650. The bracket 346 includes features 3443. and 34413 for abutting the tapered projections 323a and 3231), respectively, of the pump interface assembly 300. The bracket 346 also includes a cutout 330 sized and shaped for aligning with the docking port 342 and the slot 332 on the pump driver housing Operationally, the seal n the pump ace ly 300 and the ?uid pump assembly 106 is formed in two steps, illustrated with reference to Figures 9 and 10.

In a ?rst step, the ?ange 328 is positioned within the docking port 342, while the tapered projections 323a and 323b are positioned on the clockwise side next to corresponding features 344a and 34413 on the bracket 346. In a second step, as shown by the arrows 345, 347 and 349 in Figure 9, the pump interface assembly 300 and the ?uid pump assembly 106 are rotated in opposite directions (e.g., rotating the pump interface assembly 300 in a counter ise direction while holding the pump assembly 106 ?xed) to slide the ?ange 328 into the slot 332 ofthe docking port 342. At the same time, the tapered projections 323a and 323i) slide under the bracket features 344a and 344b, respectively, engaging inner surfaces ofthe t features 344a and 344i) with tapered outer es VI ofthe tapered projections 323a and 32% to draw the inner side 306 ofthe pump interface assembly 300 toward the pump driver 334 and to interlock the ?ange 328 with the docking ports 342, and the tapered projections 323a and 323i) with the bracket es 344a and 3441) to form the ?uid tight seal between the two assemblies 300 and 106.

Having described the illustrative organ care system 100 ?om a system, operational and component point ofview, rative control systems and methods for achieving operation of the system 100 are next discussed. More particularly, Figure ll s a block diagram of an illustrative control scheme for the system 100. As described above with reference to Figure l, the system 100 includes a controller 150 for controlling operation of the system 100. As shown, the controller 150 connects interoperationally with the following six subsystems: an operator interface 146 for assisting an Operator in monitoring and controlling the system 100 and in ring the condition of the heart 102; a data acquisition subsystem 147 having various sensors for obtaining data relating to the heart 102 and to the system 100, and for conveying the data to the controller 150; a power management subsystem 148 for providing fault tolerant power to the system 100; a heating subsystem 149 for providing controlled energy to the heater 110 for warming the ion ?uid 108; a data management subsystem 151 for storing and maintaining data relating to operation of the system 100 and with respect to the heart 102; and a pumping subsystem 153 for controlling the pumping ofthe perfusion ?uid 108 through the system 100. It should be noted that although the system 100 is described conceptually with reference to a single controller 150, the control ofthe system 100 may be distributed in a plurality of controllers or processors. For example, any or all of the described subsystems may include a dedicated processor/controller. Optionally, the dedicated processors/controllers of the various subsystems may communicate with and via a central controller/processor.

Figures 12 - 173! illustrate the interoperation of the s subsystems ofFigure 11. Referring ?rst to the block diagram of Figure 12, the data ition subsystem 147 includes s for obtaining information ning to how the system 100 and the heart 102 is functioning, and for communicating that information to the controller 150 for processing and use by the system 100. As described with t to Figure 1, the sensors of subsystem 147 include, without limitation: temperature sensors 120, 122 and 124; pressure sensors 126, 128, and 130; ?ow rate sensors 134, 136 and 138; the oxygenation/hematocrit sensor 140; and electrodes 142 and 144. The data acquisition subsystem 147 also includes: a set of Hall sensors 388 and a shaft encoder 390 from the perfusion pump assembly 106; battery sensors 362a~3 620 for sensing Whether the batteries 352a-352c, respectively, are suf?ciently charged; an external power available sensor 354 for sensing whether external AC power is available; an operator interface module battery sensor 370 for sensing a state of charge ofthe Operator interface module battery; and a gas pressure sensor 132 for sensing gas ?ow from the gas ?ow chamber 176. How the system 100 uses the information ?om the data acquisition subsystem 147 will now be described with regard to the heating 149, power management 148, pumping 153, data management 151, and or ace 146 subsystems, shown in further detail in s 13—171, respectively.

The heating subsystem 149 is depicted in the block diagram of Figure 13. With continued reference also to Figure 1, the heating tem 149 controls the temperature of the perfusion ?uid 108 within the system 100 h a dual feedback loop approach.

In the ?rst loop 251 (the perfusion ?uid temperature loop), the perfusion ?uid temperature thermistor sensor 124 provides two (fault tolerant) s 125 and 127 to the ller 150. The signals 125 and 127 are tive of the ature of the perfusion fluid 108 as it exits the heater assembly 110. The controller 150 regulates the drive signals 285 and 287 to the drivers 247 and 249, tively. The drivers 247 and 249 convert corresponding l level signals 285 and 287 from the controller 150 to heater drive signals 281 and 283, respectively, having suf?cient current levels to drive the ?rst 246 and second 248 heaters to heat the perfusion ?uid 108 to Within an operator selected temperature range. In response to the controller 150 detecting that the perfusion ?uid temperatures 125 and 127 are below the cperator~selected temperature range, it sets the drive signals 281 and 283 to the ?rst 246 and second 248 heaters, respectively, to a suf?cient level to continue to heat the ion ?uid 108. Conversely, in response to the controller 150 detecting that the perfusion ?uid temperatures 125 and 127 are above the operator-selected temperature range, it decreases the drive signals 281 and 283 to the ?rst 246 and second 248 heaters, respectively. In response to detecting that the temperature of the perfusion fluid 108 is Within the operator—selected temperature range, the ller 150 ins the drive signals 281 and 283 at censtant or substantially constant levels.

Preferably, the controller 150 varies the drive signals 281 and 283 in ntially the same manner. r, this need not he the case. For example, each heater 246 and 248 may respond differently to a particular current or voltage level drive signal. In such a case, the controller 150 may drive each heater 246 and' 248 at a slightly different level to obtain the same ature from each. According to one feature, the heaters 246 and 248 each have an associated calibration factor, which the controller 150 stores and employs when determining the level of a ular drive signal to provide to a particulanheater to achieve a particular temperature result. In certain con?gurations, the controller 150 sets one ofthe thermistors in dual sensor 124 as the default thermistor, and will use the temperature reading from the default thermistor in instances where the stors give two different temperature readings. In certain con?gurations, where the temperature readings are within a pro-de?ned range, the controller 150 uses the higher ofthe two readings. The drivers 247 and 249 apply the heater drive signals 281 and 283 to corresponding drive leads 282a and 282b on the heater assembly 110.

In the second loop 253 (the heater temperature loop), the heater temperature sensors 120 and 12?. provide signals 121 and 123, indicative of the temperatures of the s 246 and 243, respectively, to the controller 150. According to the illustrated ment, a ature ceiling is established for the heaters 246 and 248 (e.g., by default or by operator selection), above which the atures of the heaters 246 and 248 are not allowed to rise. As the temperatures of the heaters 246 and 248 rise and ch the temperature ceiling, the sensors 121 and 123 te the same to the controller 150, which then lowers the drive signals 281 and 283 to the heaters 246 and 248 to reduce or stop the supply ofpower to the heaters 246 and 248. Thus, while a low temperature signal 125 or 127 ?om the perfusion ?uid temperature sensor 124 can cause the controller 150 to increase power to the heaters 246 and 248, the heater temperature sensors 120 and 122 ensure that the heaters 246 and 248 are not driven to a degree that would cause their respective heater plates 250 and 252 to become hot enough to damage the perfusion ?uid 108. According to various illustra?Ve embodiments, the centroller 150 is set to maintain the perfusion fluid temperature at between about 32° C and about 37° C, or between about 34° C and about 36° C. According to a further illustrative embodiment, the controller 150 is set to limit the maximum temperature ofthe heater plates 250 and 252 to less than abOut 38° C 39° C , , 40° C, 41° C, or42° C.

As can be seen, the second loop 253 is con?gured to override the ?rst loop 251, if necessary, such that temperature readings from temperature Sensors 120 and 122 indicating that the heaters 246 and 248 are approaching the maximum allowable temperature override the effect of any low temperature signal ?om the perfusion ?uid ature sensor 124.

In this respect, the subsystem 149 ensures that the ature of the heater plates 250 and 252 do not rise above the maximum allowable temperature, even ifthe temperature ofthe perfusion ?uid 108 has not reached the operator~sclected temperature value. This override feature is particularly important during failure situations. For example, ifthe per?lsion ?uid ature sensors 124 both fail, the second loop 253 stops the heater assembly 110 from overheating and damaging the ion fluid 108 by switching control exclusively to the heater temperature sensors 120 and 122 and dropping the temperature set point to a lower value. According to one feature, the controller 150 takes into account two time constants assigned to the delays ated with the temperature measurements from the heaters 246 and 248 and perfusion ?uid 108 to optimize the dynamic se ofthe temperature controls.

Figure 14 depicts a block diagram of the power management system 148 for providing fault tolerant power to the system 100. As shown, the system 100 may be powered by one offour sources - by an external AC source 351 (e.g., 60 Hz, 120 VAC in North America or 50Hz, 230 VAC in Europe) or by any of three independent batteries 352a - 3520. The controller 150 receives data from an AC line voltage availability sensor 354, which indicates whether the AC voltage 351 is ble for use by the system 100.

In response to the controller 150 detecting that the AC voltage 351 is not available, the controller 150. s the power switching circuitry 356 to provide system power high 358 from one of the batteries 352a-352c. The controller 150 determines from the y charge sensors 362a~362c which ofthe available batteries 35221—3520 is most fully charged, and then switches that y into operation by way ofthe switching network 356.

Alternatively, in response to the ller 150 ing that the external AC voltage 351 is available, it determines r to use the available AC voltage 351 (e.g., subsequent to recti?cation) for providing system power 358 and for providing power to the user interface module 146, for charging one or more ofthe batteries 352a—352c, and/or for charging the internal battery 368 ofuser interface module 146, which also has its own internal r and charging controller. To use the available AC voltage 351, the controller 150 draws the AC voltage 351 into the power supply 350 by signaling through the switching system 364. The power supply 350 receives the AC e 351 and converts it to a DC current for providing power to the system 100. The power supply 350 is universal and can handle any line frequencies or line voltages commonly used throughout the world. According to the illustrative embodiment, in response to a low battery indication from one or more ofthe battery sensors 36211-3620, the controller 150 also directs power via the switching network 364 and the charging t 366 to the appmpn'ate battery. In se to the controller 150 receiving a low battery signal from the sensor 370, it also or alternatively directs a charging voltage 367 to the user interface battery 368. According to another feature, the power management subsystem 148 selects batteries to power the system 100 in order of charged ?rst, preserving the most charged batteries. Ifthe battery that is currently being used to power the system 100 is d by the user, the power management subsystem 148 automatically switches over to_the next least~charged battery to continue ng the system 100.

According to another feature, the power management tem 148 also employs a lock-out mechanism to prevent more than one of the batteries 352a—3 52c from being d from the system 100 at a given time. Ifone battery is removed, the other two are mechanically locked into position within the system 100. In this respect, the system 148 provides a level of fault tolerance to help ensure that a source r 358 is always available to the system 100.

The pumping subsystem 153 ofFigure 11 will now be described in further detail with reference to Figures 15 and 16. More particularly, Figure 15 is a conceptual block diagram depicting the illustrative pumping subsystem 153, and Figure 16 shows an exemplary ECG 414 of a heart 102 synchronized with an exemplary wave 385 depicting pumping output by the subsystem 153. The ECG 414 shown in Figure 16 has P, Q, R, S, T, and U peaks. The pumping subsystem 153 includes the ion ?uid pump 106 interoperationally connected to the pump interface assembly 300, as bed in more detail above with reference to s 8A—10. As shown in Figure 15, the controller 150 Operates the pumping subsystem 153 by sending a drive signa1339 to a brushless three- phase pump motor 360 using Hall Sensor feedback. The drive signal 339 causes the pump motor shaft 337 to rotate, thereby causing the pump screw 341 to move the pump driver 334 up and/or down. According to the illustrative embodiment, the drive signal 339 is controlled to change a rotational direction and rotational velocity ofthe motor shaft 337 to cause the pump driver 334 to move up and down cyclically. This cyclical motion pumps the per?rsion ?uid 108 h the system 100.

In ion, the controller 150 receives a ?rst signal 387 from the Hall sensors 388 positioned integrally within the pump motor shaft 337 to indicate the position ofthe pump motor shaft 337 for purposes of commutating the motor winding currents. The controller 150 receives a second higher resolution signal 389 from a sha? encoder sensor 390 indicating a precise rotational position of the pump screw 341. From the current motor commutation phase on 387 and the current rotational position 389, the controller 150 calculates the appropriate drive signal 339 (both magnitude and polarity) to cause the necessary rotational change in the motor shalt 337 to cause the appropriate vertical position change in the pump screw 341 to achieve the desired pumping action. By g the magnitude ofthe drive signal 339, the controller 150 can vary the pumping rate (l.6., how often the g cycle repeats) and by varying the rotational direction s, the controller 150 can vary the pumping stroke volume (e.g., by varying how far the pump driver 334 moves during a cycle). Generally speaking, the cyclical pumping rate regulates the ile rate at which the perfusion ?uid 108 is provided to the heart 102, while (for a given rate) the pumping stroke regulates the volume ofper?ision ?uid 108 provided to the heart 102.

Both the rate and stroke volume affect the flow rate, and indirectly the re, of the perfusion ?uid 108 to and from the heart 102. As mentioned with regard to Figure l, the system includes three ?ow rate sensors 134, 136 and 138, and three pressure sensors 126, 128' and 130. As shown in Figure 15, the sensors 134, 136, and 138 provide corresponding flow rate signals 135, 137 and 139 to the controller 150. Similarly, the sensors 126, 128 and 130 e corresponding pressure signals 129, 131 and 133 to the controller 150. The controller 150 s all ofthese signals in feedback to ensure that the commands that it is providing to the perfusion pump 106 have the desired effect on the system 100. In some instances, and as sed below in further detail with nce to Figures 17A-17J, the controller 150 may generate various alarms in reSponse to a signal indicating that a ular flow rate or ?uid pressure is outside an acceptable range.

Additionally, employing multiple sensors enables the controller 150 to distinguish between a mechanical issue (e.g., a conduit blockage) with the system 100 and a biological issue with the heart 102.

According to one feature of the invention, the pumping system 153 may be con?gured to control the position of the pump driver 334 during each moment ofthe pumping cycle to allow for ?nely tuned pumping rate and volumetric pro?les. This in turn enables the g system 153 to supply per?jsion fluid 108 to the heart with any desired pulsatile pattern. According to one illustrative embodiment, the rotationai on ofthe shaft 33’? is sensed by the shaft encoder 390 and adjusted by the controller 150 at least about 100 ents per revolution. In another illustrative embodiment, the rotational on ofthc shaft 337 is sensed by the shaft encoder 390 and adjusted by the controller 150 at least about 1000 increments per tion. According to a further illustrative embodiment, the rotational position of the shaft 337 is sensed by the shaft encoder 390 and adjusted by the controller 150 at least about 2000 increments per revolution. The vertical position ofthe pump screw 341 and thus the pump driver 334 is calibrated initially to a zero or a ground position, corresponding to a reference position of the pump screw 341.

According to the illustrative embodiment, the positional precision of the pumping tem 153 enables the controller 150 to precisely regulate the pumping of the perfusion fluid 108 through the heart 102. This process of synchronizing the 'lo ?ow of the perfusion ?uid to the heart’s natural rate is referred to herein as "r~wave synchronization," which is bed with continued reference to Figures 2, 15, and 16. A normally ning heart has a ase pumping cycle —- diastole and systole. During the diastolic phase, also known as the "resting phase," the heart’s atria 157 and 15?. contract, causing valves to open between the atria 157 and 152 and the ventricles 154 and 156 to allow blood to ?ow into and load the cles 154 and 156. During the systolic phase, the loaded ventricles eject the blood, and the atria 157 and 152 are opened and ?ll with blood. The cyclical expansion and contraction of the heart 102 during this process can be ented by graphing the heart’s ventricular ECG wave form, shown at 414 in Figure 16. Figure 16 depicts the ECG rm 414 synchronized with an exemplary wave 385 representative of a pumping output by the subsystem 153.

The pumping subsystem 153 is con?gured to provide the maximum output at a time that will result in delivery of?uid 108 to the heart 102 at the most bene?cial time. In the illustrated embodiment, in retrograde mode, the pumping subsystem 153 is con?gured to pump ?uid 108 toward the heart 102 so that the maximum pump output 382 occurs during the diastolic phase of the heart, which begins after the S peak shown in Figure 16 arid is when the left ventricle 156 has ?nished ejecting perfusion ?uid 108 through the aorta 158. Timing the pump output in this manner allows the user to ze the injection ofperfusion ?uid 108 through the aorta 158 and into the coronary sinus 155. The timed g is accomplished by starting the pumping at point 377 on wave 385, which is a point prior to point 382 and corresponds to the peak of the s r—wave pulse 380 and the middle ofventricular systole. The point 377 is selected to account for elay between the time a signal is provided from the controller 150 to start pumping the ?uid and the time of actual delivery of the pumped ?uid 108 to the heart 102. In another example, during normal ?ow mode where the left side ofthe heart ?lls and ejects perfusion ?uid (as described in more detail with reference to Figure 24A), the controller 150 synchronizes the pumping tem 153 to start g at a ?xed period oftime after the r-wave 380, so as to match the natural ?lling cycle ofthe left atrium 152. The synchronization may be adjusted and ?ne-tuned by the or through a pus—programmed routine in the operating software on the system 100 and/or by manually operating the controls of the user interface display area 410, as bed in more detail below in reference to Figures 17A— 17.1.

To achieve the synchronized pump output, the controller 150 predicts When the heart’s r-wave pulses 380 will occur and causes the pump to pump at the appropriate time during the ECG 414. To make this prediction, the controller 150 measures the length various r-wave pulses 380 from the electrical signals 379 and 381 provided from the electrodes 142 and 144, respectively. From these pulses, the controller 150 tracks the time that elapses from one pulse 380 to the next, and uses this information to calculate a running average of the leng?i oftime separating two sequential r—wave pulses. From this information, the controller 150 projects the time of the next r-wave (and ?rom the projection determines the time prior to or after that projected r~wave when the pumping should start to achieve l output delivery) by adding the average time separating two sequential r-wave pulses to the time of the previous r-Wave 380. Based on this running average of separation time between r-waves, the controller 150 has the option to adjust the, time ofpump output in relation to subsequent r-waves, as re?ected in the movement of wave 385 to the left or the right along the ECG 414 as signi?ed by the arrow 383 in Figure 16. Adjusting the wave 385 thus allows the user to adjust and customize the timing of output by the pump 106 so as to optimize the ?lling of the heart. In addition, the pump 106 may also be adjusted to se or decrease the pump stroke volume to customize the volume of fluid 108 provided by the pump 106, and this may be done either in concert with or independent of the r-wave synchronization.

It should be noted that although the subsystem 153 particularly syncln'onizes with the r-wave cycle 385, this need not be the case. In alternative illustrative embodiments, the subsystem 153 may pump in synchrorricity with any available characteristic ofthe heart, including ?uid pressures into or out of a particular chamber or vessel. Also, the subsystem 153 may be programmed to pump in any ary pattern, whether periodic or l0 Referring back to Figure 1 1, the data management subsystem 151 es and stores data and system information from the various other subsystems. The data and other ation may be downloaded to a portable memory device and organized within a database, as desired by an operator. The stored data and ation can be accessed by an operator and displayed through the operator ace subsystem 146.

Turning now to the operator interface subsystem 146, Figures l7A—l 7J show various illustrative display screens ofthe operator interface tem 146. The display screens ofFigures 17A~17J enable the operator to receive information horn and provide commands to the system 100. Figure 17A depicts a top level "home page" display screen 400 according to an illustrative embodiment ofthe invention. From the display screen 400 an operator can access all of the data available from the data ition tem 147, and can provide any desired ds to the ller 150. As described in more detail in reference to Figures 1738-17], the display screen 400 of Figure 17A also allows the operator to access more detailed display screens for obtaining information, providing ' commands and setting Operator selectable parameters.

With continued nce to Figure 1, the diSplay screen 400 includes a display area 402, which shows a number of numerical and graphical indications pertaining to the operation of the system 100. In particular, the display area 402 includes a cal reading of the aorta output pressure (AOP) 404 ofthe perfusion fluid 108 exiting the aorta interface 162 on the organ chamber assembly 104, a wave form depiction 406 ofthe aortic ?uid pressure (AOP) 404, and an ADP alarm image 408 indicating whether the fluid pressure 404 is too high or too low (the alarm 408 is shown as "of’ in Figure 17A). The display screen 400 also includes a display area 410 having a numerical indication 412 of the rate at which the heart 102 is beating, an ECG 414 of the heart 102, a heart rate (HR) alarm image 416 indicating whether the HR 412 exceeds or falls below operator set thresholds, and a time log 418 indicating how long the system 100 has been running, including priming time (discussed in further detail below with nce to Figure 29.4) A numerical display 419 shows the amount oftime for which the system 100 has been supporting the heart 102. The indicator alarm 413 indicates when an operator preset time limit is encoded.

The y screen 400 includes a number of additional y areas 420, 424, 432, 438, 444, 450, 456, 460, 462, 466, 472, 480, and 482. The display area 420 shows a numerical reading of the pulmonary artery pressure (PAP) 422. The PAP 422 is an indication of the pressure of the perfusiou ?uid 108 ?owing from the heart’s ary artery 164, as ed by the pressure sensor 130. The display area 420 also provides a PAP alarm indicator 424, which signals when the PAP 422 is outside an Operator preset range. The display area 426 indicates the temperature (Temp) 428 ofthe perfusion ?uid 108 as it exits the heater 110. The display area 426 also includes a Temp alarm indicator 43 0, which signals in response to the Temp 428 being outside of an operator preset range.

The upper limit of the operator preset range is shown at 427. The display area 432 shows a numerical reading of the crit (HOT) 434 ofthe perfusion ?uid 108, and an HCT alarm indicator 436 for signaling the or ifthe HCT 434 falls below an operator preset threshold. The display area 438 shows the oxygen saturation (SvOz) 440 of the iOn ?uid 108. The display area 438 also includes a 8x0; alarm 442 for indicating if the SvOz 440 ofthe perfusion fluid 108 falls below an operator preset threshold. The display area 444 indicates the aorta output ?ow rate (AOF) 446 of the perfusion ?uid 108 as it ?ows out of the aorta 158. The AOF 446 is measured by the ?ow rate sensor 134.

The AOF alarm 448 indicates whether the flow rate 446 falls outside of an operator preset range. The y area 450 shows the organ chamber ?ow rate (CF) 452. The CF 452 is an indication ofthe flow rate ofthe per?asion ?uid 108 as it exits the organ chamber 104, as measured by the flow rate sensor 136. The diSplay area 450 also includes a CF alarm 454, which signals in response to the CF 454 falling outside of an operator preset range.

The display area 456 includes a graphic 458 for indicating when a ?le transfer to the memory card is occurring.

The display area 460 shows a graphical representation 459 of the degree to which each of the batteries 352a—3520 (described above with reference to Figure 14) is charged.

The display area 460 also provides a numerical indication 461 of the amount of time remaining for which the batteries 35123—3 52c can continue to run the system 100 in a current mode of ion. The display area 462 identi?es whether the operator interface module 146 is Operating in a ss 464 fashion, along with a graphical representation 463 of the strength ofthe wireless connection between the operator interface module 146 and the remainder ofthe system 100. The display area 462 also provides graphical indication 467 of the charge remaining in the Operator interface module battery 368 (described above with reference to Figure 14) and a numerical indication 465 of the amount oftime remaining for which the operator interface module battery 368 can support it in a wireless mode of ion. The diSplay area 466 indicates the ?ow rate 468 of oxygen from the gas ?ow chamber 176. It also provides a graphical indication 469 ofhow ?ill an onboard oxygen tank is, and a numerical indication 470 of the amount oftime remaining before the onboard oxygen taiik runs out. The y area 472 shows the heart rate ofthe heart 102, and the amount of time 476 for which the heart 102 has been cannulated onto the system 100. This ?eld is duplicative of the ?eld 419 mentioned above. The y areas 480 and 482 Show the t time and date, respectively, of operation of the system 100.

Acmating a dial (or mouse, or other control device), such as the dial 626 shown in Figure 18A, on the operator interface 146 opens a con?guration menu 484, such as shown in the display screen 401 ofFigures 178. As shown, aCCessing the ration menu 484 covers the display areas 402 and 410 so they no longer show the graphical ions of the pressure 406 and the heart rate 414, but continue to display critical alpha/numeric information. As also shown, all other display areas remain unchanged. This enables an operator to adjust operation ofthe system 100 while continuing to monitor critical information. According to one feature, the con?guration menu 484 allows the operator to pre-program desired operational parameters for the system 100. Using the display screen 401, the operator can dit worldng and lic (or rade) mode alarms by selecting the ?elds 488 and 490, respectively. The operator can set particular ECG and LAP cal options by selecting the fields 492 and 494. Additionally, the operator can set oxygen ?ow rate and perfusion ?uid temperature by selecting the ?elds 496 and 498, respectively. Selecting the ?eld 500 enables the operator to set the time and date, while selecting the ?eld 502 enables the operator to select the language in which information is displayed. At the bottom of the display ?eld 484, the operator has the option to return 504 to the display screen 400, cancel 506 any changes made to operational settings, save 508 the changes as new defaults, or reset 510 the operational settings to factory ts.

Referring to Figures 17C-17D, ing the view/edit working mode alarms ?eld 483 causes the working mode alarm dialog 512 ofFigure 171) to open within the display ?eld 484 of Figure 17C. The working mode dialog 512 displays the parameters ated with normal ?ow mode ibed above with reference to Figures 1 and 3) and includes a ?eld for setting numerical thresholds for each ofthe normal ?ow mode alarms. More speci?cally, the dialog 512 includes: CF alarm ?eld 514; PAP alarm ?eld 516; AOP alarm ?eld 518; LAP alarm ?eld 520; perfusion ?uid Temp alarm ?eld 524; SvOz alarm ?eld 526; HCT alarm ?eld 528; and HR alarm ?eld 530. By selecting a particular alarm ?eld and actuating the up 532 and/or down 534 arrows, at operator can adjust the acceptable upper and/or lower thresholds for each ofthe parameters associated with each ofthe . The dialog 512 also includes alarm graphics 536a~536i, each ofwhich being associated with a particular normal ?ow mode alarm. The operator can enable/disable any of the above normal flow mode alarms by selecting the associated alarm graphic 536a— 536i. Any changes made using the dialog 512 are ed in corresponding ?elds in the display screen 400 ofFigure 17A.

Referring to Figures 17A, 17B and 17B, selecting the view/edit non-working mode alarms ?eld 490 causes the resting mode alarm dialog 538 ofFigure 1713 to Open within the display ?eld 484 ofFigure 170. The resting mode dialog 538 diaplays the parameters associated with retrograde ?ow mode (described above with reference to Figures 1 and 4) and includes a ?eld for g numerical thresholds for each ofthe rade ?ow mode alarms. ing to the illustrative embodiment, the available alarms for the normal and retrograde ?ow modes are r, but not necessarily the same. Additionally, even for those that are the same, the thresholds may differ. ingly, the invention enables the operator to select different alarms and/or different thresholds for each ?ow mode of operatiou. More speci?cally, the dialog 538 includes: CF alarm ?eld 540; PAP alarm ?eld 542; AOF alarm ?eld 544; AOP alarm ?eld 546; LAP alarm ?eld 548; perfusion ?uid Temp alarm ?eld 550; SvOz alarm ?eld 552; HCT alarm ?eld 556; and HR alarm ?eld 558. By ing a particular alarm ?eld and actuating the up 560 andlor down 562 arrows, an operator can adjust the acceptable numerical upper and/or lower thresholds for each of the parameters associated with each ofthe alarms. The dialog 538 also includes alann graphics 564a—564i, each ofwhich being associated with a particular normal ?ow mode alarm. The operator can enable/disable any ofthe above normal ?ow mode alarms by selecting the associated alarm graphic 564a—564i. As is the case of the dialog 512, any changes made using the dialog 538 are reflected in corresponding ?elds in the display screen 400 of Figure 17A. In one implementation, the system 100 may be con?gured to automatically switch between sets of alarm limits for a given ?ow mode upon changing the ?ow mode.

Referring to Figures 17A, 17B, 17F and 176, the or ace 146 also provides cal mechanisms for adjusting various parameters. For example, as noted above in reference to Figure 16, one advantage of the user display area 402 is that it allows the operator to monitor (and adjust) the g ofthe subsystem 153. Display area 410 identi?es the ECG waveform 414 of the heart 102, and diSplay 402 shows in wave form 406 the pressure of ?uid ?owing through the aorta. In these two-displays the operator can monitor the effect ofthe pumping pro?le on the heart’s EGC 414, which allows the user to adjust the stroke volume of the pumping subsystem 153, to adjust the rate of the pumping subsystem 153 (and thus the ?ow~rate ofthe ?uid 108 being pumped through the system 100), to manually impose, or adjust a time of, ?ring of the subsystem (e.g., by ng a ?xed delay between the r-wave 380 and the beginning ofthe pumping cycle), or to automatically m the pumping subsystem 153 to pump at a predetermined time along the heart’s ECG waveform 414, as needed to ly ?ll the heart according to Whether the heart is being perfused in retrograde or normal mode. These g adjustments may be made by use of the various graphical frames of the operator interface 146. By way ple, in response to a operator selecting the ECG graphic frame option 492 d in the display ?eld 484 ofthe display screen 401, the operator interface 146 displays the dialog 568 ofFigure 17F. The dialog 568 shows a graphical representation 572 ofthe ECG 414 along with a cursor 570. The position of the cursor 570 indicates the point at which the pumping tem 153 will initiate an output pumping stroke 6.6., the portion of the pumping cycle at which the pump motor 106 will push perfusion ?uid 108 to the heart 102) relative to the ECG 414 ofthe heart 102. By rotating a mechanical knob 626 (shown in Figures 18A and 18B) on the operator interface 146, the Operator moves the position of the cursor 570 to adjust when the pumping subsystem 153 will initiate the output pumping stroke relative to the r-wave pulse 380. As described above with regard to Figures 15 and 16, the pumping subsystem 153 receives an r—wave signal 380 from the ECG sensors 142 and 144. The pumping subsystem 153 uses the r- wave signal 380 along with the pumping adjustment information from the cursor 570 to synchronize perfusion ?uid pumping with the beating of the heart 102. In another example, in‘response to the operator pressing the pump adjust button 625, the operator interface 146 displays the dialog 574 ofFigure 17G. From the dialog 574, the operator can select the pointer 576 and rotate the knob 626 to turn the pump motor 106 on and off. Additionally, the operator can select the bar graphic 578 and rotate the knob 626 to adjust the volume of ?uid being pumped, which is displayed in liters/minute.

The operator interface 146 also provides a plurality ofwanting/reminder messages.

By way of example, in Figure 17H, the operator interface 146 displays a message to remind the operator to connect to AC power to recharge the batteries. This message s, for example, in response to the controller 150 ing an impending low battery condition. The operator interface 146 displays the message ofFigure 17I to con?rm that the user wishes to enter standby mode and to remind the operator to insert a portable ' memory device, such as magnetic or optical disk, a le disk drive, a ?ash memory card or other suitable memory device, to download and store information regarding a particular use of the system 100. The operator interface 146 displays the error messages, such as the error message of Figure 171, in response to an identi?able fault occurring. The error messages ofFigure 171 include, for example, error information 580 to aid a service technician in sing and/or repairing the fault.

Having described an illustrative control systems and methods for ing ion ofthe system 100, illustrative ical es ofthe system 100 will now be discussed, along with an illustrative division of ents between the single use disposable module 634 and multiple use module 650 units. More particularly, Figures B Show a mechanical implementation 600 of the system of Figure 1, according to an illustrative embodiment ofthe invention. As shown, the rative implementation 600 includes a housing 602 and a cart 604. The g 602 conceptually divides into upper 602a and lower 602b housing sections, and includes front 606a, rear 60 613, left 606e, and right 606d sides. The cart 604 includes a platform 608 and wheels 10d for transporting the system 600 from place to place. A latch 603 secures the housing 602 to the cart 604. To further aid in portability, the system 600 also includes a handle 610 hinge mounted to the upper section 602a of the left side 6060 ofthe housing 602, along with two rigidly mounted handles 612a and 612b mounted on the lower section 6021) ofthe left 606C and right 606d sides of the housing 602.

The housing 602 further includes a removable top 614, and a front panel 615 having an upper panel 613, and a mid panel 616 hinged to a lower panel 617 by hinges 616a and 616b. The t0p 614 includes handles 614a and 614b for aiding with removal. In the illustrated embodiment, the upper panel 613 is screwed, bolted or otherwise adjoined to the top 614, such that removal of the top 614 also removes panel 613.

As shown in Figure 18A, the system 600 es an AC power cable 618, along with a frame 620 for securing the power cable 618, both located on the lower section 602b of the left side 6060 ofthe housing 602. A so?ware reset switch 622, also located on the lower n 60213 of the left side 602c, s an or to restart the system software and electronics.

As shown in Figures 18A and 183, the implementation 600 also includes the operator interface module 146, along with a cradle 623 for holding the operator interface module 146. The operator interface module 146 includes a display 624 for displaying information to an operator, for example, by way of the display screens of Figures 17A~17I.

As mentioned above, the operator interface module 146 also includes a rotatable and depressible knob 626 for selecting between the various parameters and display screens of Figures 17A—l7J. The knob 626 may also be used to set parameters for tic control of the system 100, as well as to provide manual control over the ion of the system 100. For example, the knob 626 may be used to provide instructions to the controller 150 to increase perfusion ?uid ?ow rates, gas flow rates, etc. As also discussed above with regard to Figures 1, l4 and l7A-l7J, the operator ace module 146 includes its own battery 368 and may be removed from the cradle 623 and used in a wireless mode. While in the cradle 623, power connections enable the operator interface module 146 to be charged. As shown, the operator interface module also es l buttons 625 for controlling the pump, ing or disabling alarms, entering or g standby mode, entering or adjusting ECG synchronization mode, and starting the ion clock, which initiates the display ofdata obtained during organ care.

As shown in Figure 18B, the illustrative implementation 600 also includes a battery compartment 628 and an oxygen tank bay 630, both located on the lower section 602}: of the right side 606d ofthe housing 602. As shown, the battery compartment 628 houses the three system batteries 352a-352c, described above with regard to Figure 14. According to one feature, the battery compartment 626 includes three battery locks 632a-632c. As described above with respect to Figure 14, the battery locks 6323-632c interoperate mechanically so that only one ofthe three batteries 352a-352c may be removed at any given time.

The able module 634 and the multiple use unit 650 are constructed of material that is durable yet light-weight. In some illustrative embodimentS, polycarbonate plastic is used to form one or more of the components of the units 634 and 650. To further reduce the , the chassis 635 and the multiple use module s 602 are formed from low weight materials such as, for e, carbon ?ber epoxy composites, polycarbonate ABS—plastic blend, glass reinforced nylon, acetal, straight ABS, aluminum or magnesium According to one illustrative embodiment, the weight ofthe entire system 600 is less than about 85 pounds, including the multiple use module, heart, batteries, gas tank, and priming, nutritional, preservative and perfusion ?uids, and less than about 50 pounds, excluding such items. According to another illustrative embodiment, the weight of the disposable module 634 is less than about 12 , excluding any solutions.

According to a further illustrative embodiment, the multiple use module 650, ing all , ies 352a—352c and oxygen supply 172, weighs less than about 50 pounds.

With continued reference to Figures l9A-19C, various views are shown ofthe implementation 600 ofFigures 18A and 18B with the top 614 and upper front panel 613 removed and the front mid panel 616 open, according to an illustrative embodiment of the invention. With reference to Figures 19A-19C, the system 100 is structured as a single use disposable module 634 (shown and described in detail below with reference to Figures 24A~250) and a multiple use module 650 (shown without the single use module in Figure ). As discussed in r detail below, according to one feature of the illustrative embodiment, all of the blood contacting components ofthe system 100 are included in the single use disposable module 634 so that after a use, the entire single use module 634 may be discarded, a new module 634 installed, and the system 100 available for use again within a very briefamount oftime.

According to the illustrative embodiment, the single use module 634 includes a chassis 635 for supporting all of the components of the single use module 634. As described in more detail with regard to Figures C. the components of the single use module 634 e the organ r assembly 104, described above in detail with respect to Figures 5A~5F, the per?ision ?uid reservoir 160, the oxygenator 114, the perfusion fluid pump interface 300, and all of the various ?uid ?ow conduits and peripheral monitoring components 633.

As shown in Figures 19A—20A, with the top 614 removed and the front panel 616 Open, an operator has easy access to many ofthe components ofthe disposable 634 and multiple use 650 modules. For example, the operator may install, remove and View the levels of the nutrient 116 and preservative 118 supplies of the ional subsystem 115.

The operator may also control operation of the nutrient 116 and preservative 118 infusion pump 182. The Operator may also ate an organ, such as the heart 102, into the organ chamber assembly 104. As described in detail below with reference to Figures ZlA-Zlc, this. con?guration also provides the Operator with suf?cient access to install and/or remove the single use module 634 m the multiple use module 650.

Figure 20A shows a front persPective view ofthe multiple use module 650 with the single use module 634 removed. As shown, the multiple use module 650 includes: the 'cart 604; the lower section 60213 of the g 602, along with all of the components externally mounted to it, along with those contained therein (described in further detail below, with reference to Figures 21A~210 and 23A-ZSC); the upper section 602a ofthe housing 602 and all ofthe components externally mounted to it, including the top cover 614, the handles 610, 612a, and 612b, and the front panel 616; the operator interface . 146; and the ion fluid pump motor assembly 106. As described in detail below With reference to Figures ZlA—ZIC, the multiple use module 650 also includes a bracket assembly 638 for receiving and looking into place the single use module 534.

As shown in Figure 20A and described in further detail below with reference to Figures 22A—22C, the multiple use module 650 also includes a front—end ace circuit board 636 for interfacing with a end circuit board (shown in Figure 24D at 637) of the disposable module 634. As also described in detail with reference to Figures 22A-220, power and drive signal tions between the multiple use module 650 and the disposable module 634 are made by way of corresponding electromechanical connectors 640 and 647 on the front end interface circuit board 636 and the front end circuit board 637, respectively. By way of example, the end circuit board 637 receives power for the disposable module 634 from the front~end interface circuit board 636 via the electromechanical connectors 640 and 647. The front end t board 637 also receives drive signals for various components (e.g., the heater assembly 110, and the oxygenator 114) from the controller 150 via the ?ont~end interface circuit board 636 and the electromechanical connectors 640 and 647. The ?out—end circuit board 637 and the front- end interface circuit board 636 exchange control and data signals (e.g., between the ller 150 and the disPosable module 134) by way of optical connectors (shown in Figure 22B at 648). As described in more detail with reference to Figures 22A~22F, the connector con?guration employed between the front—end 637 and front—end interface 636 circuit boards ensures that critical power and data interconnections between the single and multiple use modules 634 and 650, tively, continue to operate even during transport over rough terrain, such as may be enced during organ transport.

As shown in Figure 20A, according to another feature, the upper section 6023. of the g 602 includes a ?uid tight basin 652, which is con?gured to e any ion ?uid 108 and/or nutritional 116 and/or preservative 118 solution that may inadvertently leak. The basin 652 also prevents any leaked ?uid 108 or solution 116/118 from passing into the lower section 602b ofthe housing 602. In this way, the basin 652 shields the electronic components ofthe system 100 from any such leaked ?uid 108 or on 1 16/118. Shielded components include, for example, the power board 720 shown in and discussed in further detail below with reference to s 230 and 23D. The basin 652 includes a n 658, which extends over and shields the per?ision ?uid 131111115 106 from any inadvertently leaked ?uid. According to another feature, the basin 652 is sized to 2O accommodate the entire volume of perfusion fluid 108 (including the maintenance ons 116/118) contained Within the system 100 at any particular time.

Referring also to Figure 20B, according to a further feature ofthe illustrative embodiment, an outer side 659 ofthe pump covering portion 658 of the basin 652 includes a slot 660. As described in further detail below with reference to Figures 21A~21C and 24A, the slot 660 engages with a projection 662 on the single use module 634 during installation of the single use module 634 into the multiple use module 650.

Turning now to the installation of the single use module 634 into the multiple use module 650, Figure 21A shows a detailed view ofthe above-mentioned bracket ly 638 located on the multiple use module 650 for receiving and looking into place the single use module 634. Figure 21B shows a side perspective View of the single use module 634 being installed onto the bracket assembly 638 and into the multiple use module 650, and Figure 21C shows a side View ofthe single use module 634 installed within the multiple use module 650. With reference to Figures 21A and 21B, the bracket assembly 638 includes two mounting brackets 642a and 642b, which mount to an internal side of a back panel 654 ofthe upper housing section 602a via mounting holes 644a-644d and 646a— 646d, respectively. A cross bar 641 extends between and bly attaches to the mounting brackets 642a and 642b. Locking arms 643 and 645 are spaced apart along and radially extend from the cross bar 641. Each locking arm 643 and 645 includes a respective rd extending locking projection 643a and 64533. A lever 639 attaches to and extends radially upward from the cross bar 641. Actuating the lever 639 in the direction of the arrow 651 rotates the locking arms 643 and 645 toward the back 606!) of the housing 602. Actuating the lever 639 in the direction ofthe arrow 653 rotates the locking arms 643 and 645 toward the front 606a of the housing 602.

As bed above with respect to Figure 10, the perfusion pump interface assembly 300 includes four ting heat staking points 321a—321cl. As shown in Figure 24A, during assembly, the tions 321a~321d are d with corresponding apertures 657a~657d and heat staked through the apertures 657a-657d into the projections 321a—321d to rigidly mount the outer side 304 ofthe pump interface assembly 300 onto the C~shaped bracket 656 ofthe single use module chassis 635.

With nce to Figures 10, 20B, 21A, 21B and 24A, during installation, in a ?rst step, the single use module 634 is lowered into the multiple use module 650 while tilting the single use module 634 forward (shown in Figure 2113). This process slides the projection 662 of Figure 24A into the slot 660 ofFigure 2013. As shown in Figure 10, it also positions the ?ange 328 of the pump interface assembly 300 Within the docking port 342 of the ion pump assembly 106, and the tapered projections 323a and 323b ofthe pump interface assembly 300 on the clockwise side ofcorresponding ones of the features 344a and 34413 of the pump ly bracket 346. In a second step, the single use module 634 is rotated backwards until g arm cradles 672 and 674 of the single use module chassis 635 engage projections 643 and 645 of spring-loaded g arm 638, forcing the projections 643 and 645 to rotate upward (direction 651), until locking projections 643a and 645a clear the height of the locking arm cradles 672 and 674, at which point the springs cause the locking arm 638 to rotate downward (direction 653), allowing g projections 643a and 645a to releasably lock with locking arm cradles 672 and 674 ofthe disposable module chassis 635. This motion causes the curved surface of 668 of the disposable module chassis projection 662 ofFigure 24A to rotate and engage with a ?at side 670 ofthe basin slot 660 of Figure 20B. Lever 639 can be used to rotate the locking am 638 uPWards (direction 651) to release the single use module 635.

As shown in Figure 10, this motion also causes the pump ace assembly 300 to rotate in a counterclockwise direction relative to the pump assembly 106 to slide the ?ange 328 into the slot 332 ofthe docking port 342, and at the same time, to slide the tapered projections 323a and 3231) under the respective t features 344a and 34%. As the d projections 323a and 3231) slide under the respective bracket features 3446. and 344b, the inner surfaces ofthe bracket features 344a and 344b engage with the d outer surfaces of the tapered projections 323a and 323i) to draw the inner side 306 of the pump interface assembly 300 toward the pump driver 334 to form the ?uid tight seal n the pump interface assembly 300 and the pump assembly 106. The lever 639 may lock in place to hold the disposable module 634 securely within the multiple use module As mentioned briefly above with reference to Figure 20A, interlocking the single use module 374 into the multiple use module 650 forms both electrical and optical interconnections between the front end interface circuit board 636 on the multiple use module 650 and the front end circuit board 637 on the single use module 634. The electrical and optical connections enable the multiple use module 650 to power, centrol and collect information ?om the single module 634. Figure 22A is a conceptual drawing showing various optical couplers and electromechanical connectors on the front end circuit board 637 ofthe single-use disposable module 634 used to icate with corresponding optical couplers and electromechanical connectors on the front end interface circuit board 636 of the multiple use module 650. Since this correspondence is one for one, the various l couplers and electromechanical connectors are described only with reference to the front end circuit board 637, rather than also depicting the ?ont end circuit board 650.

According to the illustrative ment, the front end circuit board 637 receives signals from the front end interface circuit board 636 via both optical couplers and electromechanical connectors. For example, the ?ont end circuit board 637 receives power 358 (also shown in Figure 14) from the front end ace circuit board 636 via the omechanical tors 712 and 714. The front end circuit board 637 the pOWer to the components of the single use module 634, such as the various sensors and transducers of the single use module 634. Optionally, the front end circuit board 637 converts the power to suitable levels prior to bution. The front end interface circuitboard 636 also es the heater drive signals 281a and 281b ofFigure 13 to the applicable connections 282a on the heater 246 ofFigure 6E via the omechanical tors 704 and 706.

Similarly, the electromechanical connectors 708 and 710 couple the heater drive s 283a and 283‘s ofFigure 13 to the applicable connections in 28211 of the heater 248. The front-end circuit board 637 may e a de?brillation d from the ?ont end interface circuit board 636 via the electromechanical tor 687. In response, the front end circuit board 637 generates the de?brillation signal 143 having suitable current and voltage levels, and as shown in Figure 5E, couples the signal 143 to the organ chamber assembly 104 via the electrical interface connections 235a—235b.

In another illustrative embodiment, the defibrillation command can he provided from an external source (not shown), rather than through the circuit board 63 6. As an . example, and with reference to Figure 5E and Figure 1, an external de?brillation device can be plugged into the electrical coupler 613 shown in Figure 2438, which is connected to the electrical interface connections 235a-235b. The external llation device sends a dc?brillation signal 143 through the coupler 613 and the interface connections 235a and 235b to electrodes 142 and £44. The electrodes 142 and 144 then deliver the signal 143 to the heart 102. This ative embodiment allows the user to e de?brillation (and pacing) without passing the signal 143 through the circuit boards 618, 636, and 637. An exemplary external de?brillation device may include the 2011 M-Series Portable llator.

According to the rative embodiment, the front end circuit board 637 receives signals ?om temperature, pressure, ?uid ?ow-rate, oxygentation/hematocrit and ECG sensors, ampli?es the signals, converts the signals to a digital format and provides them to the front—end interface circuit board 636 by way of optical couplers. For example, the front end circuit board 637 provides the temperature signal 121 from the sensor 120 on the heater plate 250 (shown in Figures 6A and 13) to the front end interface circuit board 636 by way of the optical coupler 676. Similarly, the horn end circuit board 637 provides the temperature signal 123 from the sensor 122 on the heater plate 252 (shown in Figures 6A and 13) to the front end interface circuit board 636 by way ofthe optical coupler 678. The front end circuit board 637 also provides the perfusion fluid temperature signals 125 and 127 from the thermistor sensor 124 (shown in Figures 6A and 13) to the front end interface t board 636 via respective optical couplers 680 and 682. Perhlsion ?uid pressure signals 129, 131 and 133 are provided from respective pressure transducers 126, 128 and 130 to the front end interface circuit board 636 via respective optical couplers 688, 690 and 692. The ?cont end circuit board 637 also provides perfusion ?uid flow rate signals 135, 137 and 139 from respective flow rate sensors 134, 136 and 138 to the front end ace circuit board 636 by way cfrcspective optical couplers 694, 696 and 698. onally, the front and circuit board 637 provides the oxygen saturation 141 and hematocrit 145 signals from the oxygen saturation sensor 140 to the front end interface circuit board 636 by way ofrespective optical couplers 700 and 702.

In other illustrative embodiments, one or more of the foregoing sensors are wired directly to the main system board 718 (described below with reference to Figure 23D) for processing and analysis, thus by—passing the front-end interface board 636 and front-end board 637 altogether. Such embodiments may be desirable where the user s to re-use one or more ofthe s prior to disposal, In one such e, the flow rate‘ sensors 134, 136 and 138 and the oxygen and hematocrit sensor 140 are electrically coupled directly to the system main board 718 through electrical coupler 611 shown in Figure 23C, thus lay-passing any connection with the circuit boards 636 and 637.

As described above with respect to Figures 11—16, the controller 150 employs the signals provided to the front end ace circuit board 636, along with other signals, to transmit data and otherwise l ion ofthe system 100. As described with respect to s J, the controller 150 also displays sensor information, and may display to the operator s alarms relating to the sensor information by way of the operator interface module 146.

Figure 22B illustrates the operation of an exemplary electromechanical connector pair of the type employed for the electrical interconnections between the circuit boards 636 and 637. Similarly, Figure 220 illustrates the operation of an optical coupler pair of the type employed for the optically d interconnections between the circuit boards 636 and 637. One advantage ofboth the electrical connectors and l couplers employed is that they ensure connection integrity, even when the system 100 is being transported over rough terrain, for example, such as being wheeled along a tarmac at an airport, being transported in an ft during bad weather conditions, or being transported in an ambulance over rough roadways. Additionally, the optical couplers electrically isolate the temperature, pressure and ECG sensors from the rest of the system 100, which prevents a de?brillation signal from damaging the system 100. The power for the front end board 637 is isolatedin a DC power supply d on the front end interface board 636.

As shown in Figure 2213, the electromechanical connectors, such as the connector 704, include a portion, such as the portion 703, located on the front end interface circuit board 636 and a portion, such as the portion 705, located on the front end circuit board 637. The portion 703 includes an enlarged head 703a mounted on a substantially ht and rigid stem 70%. The head 703 es an dly facing substantially ?at surface 708. The portion 705 includes a substantially straight and rigid pin 705 including an end 705a for contacting the surface 708 and a spring-loaded end 705b. Pin 705 can move axially in and out as shown by the directional arrow 721 while still maintaining electrical contact with the surface 708 ofthe ed head 70321. This feature enables the single use module 634 to maintain electrical t with the le use module 650 even when experiencing mechanical disturbances associated with transport over rough terrain. An advantage ofthe ?at surface 708 is that it allows for easy cleaning ofthe interior surface of the multiple use module 650. According to the illustrative embodiment, the system 100 employs a connector for the electrical interconnection between the single use disposable 634 and multiple use 650 modules. An exemplary comrector is part no. 101342 made by onnect Devices. However, any suitable connector may be used.

Optical couplers, such as the optical couplers 684 and 687 of the front end circuit board 637, are used and include corresponding counterparts, such as the optical couplers 683 and 685 of the front end interface t board 63 6. The optical transmitters and optical er portions ofthe optical couplers may be located on either circuit board 636 or 637. For example, in the case of the ECG signal 379, the optical transmitter 684 is located on the circuit board 637 for receiving the electrical signal 379 and Optically coupling it to the optical receiver 683 on the circuit board 63 6. In the case where the llator signal is transmitted through the circuit boards 636 and 637 (rather than directly to the main board 718), the optical transmitter 685 on the circuit board 636 . optically couples the signal to the Optical receiver 687 on the t board 637.

As in the case of the electromechanical connectors employed, allowable tolerance in the optical ent n the optical transmitters and corresponding optical receivers enables the circuit boards 636 and 637 to remain in optical communication even during transport over rough terrain. According to the illustrative embodiment, the system 100 uses optical couplers made under part nos. SFH485P and/or SFH203PFA by Osram. r, any suitable coupler may be used.

The rs and connectors facilitate the transmission of data within the system 100. The front-end interface circuit board 636 and the front-end board 637 transmit data pertaining to the system 100 in a paced fashion. As shown in Figure 22C, circuit board 636 transmits to the front-end board 637 a clock signal that is synchronized to the clock on the controller 150. The end circuit board 637 receives this clock signal and uses it to synchronize its transmission of system data (such as temperamres, res, ECG, ruwave detection, or other desired information) with the clock cycle ofthe controller 150. This data is zed by a processor on the front-end circuit board 637 according to the clock signal and a pre-set sequence of data type and source s (i.e. type and location of the sensor providing the data). The front-end interface circuit board 636 receives the data from the Trout-end board 637 and transmits the data set to the main board 618 for use by the controller 150 in tion, display, and system control, as described above with reference to Figures 11, 12 and 14. Additional optical couplers can be added between the multiple use module and single use module for transmission of control data from the multiple use module to the single use module, such data including heater control signals or pump control signals.

Having described the mechanical, electrical and optical onnections between the single use module 634 and the multiple use module 650, additional components of the multiple use module 650 will now be discussed with respect to Figures 23A—23D, ed by a description of the mechanical arrangement ofthe components ofthe single use module 634 with respect to Figures 24A-ZSC. As shown in Figures 23A-23D, with the walls of the housing 602 removed, in addition to those components previously discussed, the multiple use module 650 includes an on—board gas supply 172, located in the lower section 6021) of the housing 602. The gas supply 172 is ed in Figures 23A-23D as a tank, positioned within the gas tank bay 630 by a support structure 712, which abuts the tank 172. ally, the gas supply 172 may be further secured within the gas tank bay 630 by a strap and buckle assembly 714 or other suitable mechanism. With particular reference to Figure 23B and as described above with nce to Figure l, the gas supply 172. provides gas to the system 100 through the gas regulator 174 and the gas ?ow chamber 176. The gas pressure sensor 132 measures the gas pressure in the gas supply 172, and the gas pressure gauge 178 provides a visual indication of the fullness of the gas supply 172. onally, an electrical connection n the controller 150 and the gas ?ow r 176 enables the controller 150 to regulate automatically the gas ?ow into the oxygenator 114.

As shown most clearly in Figure 230, the battery bay 628 houses the batteries 352a—3520. As noted above with reference to Figure 14, a lock—out mechanism is used to prevent more than one of the batteries 35221-3520 from being removed from the battery bay 628 at a given time while the system 100 is ing.

As discussed above, the system 100 includes a plurality of interconnected circuit boards for facilitating power distribution and data ission to, ?om and within the system 100. Particularly, as discussed above with reference to Figures 22A-22E and as shown in Figure 23C, the multiple use module 650 includes a ?ont end interface circuit board 636, which optically and electromechanically couples to the front end circuit board 637 ofthe single use module 650. As also shown in Figure 230, the system 100 r includes a main board 718, a power circuit board 720, and a battery interface board 711 located on the le use module 650. The main board 718 is con?gured to allow the system 100 to be fault tolerant, in that ifa fault arises in the operation of a given circuit board (as shown in Figure 23D), the main board 718 saves pumping and heating parameters in non-volatile memory. When the system 100 reboots, it can re-capturc and continue to perform according to such parameters.

Referring to the conceptual drawing ofFigure 23D, cabling 731 brings power (such as AC power 351) from a power source 350 to the power circuit board 720 by way of tors 744 and 730. The power supply 350 converts the AC power to DC power and distributes the DC power as described above with reference to the power subsystem of Figure 14. Referring also to Figures 14 and 22A, the power circuit board 720 couples DC power and a data signal 358 via respective cables 727 and 729 ?om the connectors 726 and 728 to corresponding connectors 713 and 715 on the front end interface circuit board 636. Cable 729 carries both power and a data signal to the front end interface board 63 6.

Cable 727 carries power to the heater 110 via the front-end interface board 636. The connectors 713 and 715 t with corresponding connectors 712 and 714 (described abOVc with t to Figure 22A) on the front end circuit board 637 on the single use module 634 to provide power to the single use module 634.

As shown in Figure 23D, the power circuit board 720 also provides DC power 358 and a data signal from the connectors 732 and 734, ICSpectively, on the power circuit board 720 to corresponding connectors 736 and 738 on the main circuit board 718 by way of the cables 733 and 735. Referring also to Figures 14 and 19A, the cable 737 couples DC power 358 and a data signal from a connector 740 on the main circuit board 718 to the operator interface module 146 by way of a connector 742 on the operator ace module cradle 623. The power circuit board 720 also provides DC power 358 and a data signal from connectors 745 and 747 via cables 741 and 743 to connectors 749 and 751 on a battery interface board 711. Cable 741 carries theDC power signal and cable 743 carries the data . Battery interface board 711 distributes DC power and data to batteries 352a, 3521) and 3520. Batteries 352a, 35% and 3520 contain electronic circuits that allow them to communicate with each other to monitor the respective s, as described. above in reference to Figure 14, so that the controller 150 can monitor and control the charging and discharging ofthe batteries 52c.

According to some illustrative embodiments, the ller 150 is located on the main circuit board 718 and performs all control and processing required by the system 100. r, in other illustrative embodiments, the controller 150 is distributed, locating some processing frmctionality on the front end interface circuit board 63 6, some on the power circuit board 720, and/or some in the operator interface module 146. Suitable cabling is provided between the various circuit boards, depending on whether and the degree to which the controller 150 is distributed within the system 100.

As bed above with reference to Figures 19A-19C and ZSA-ZSC, the system 100 mechanically divides into the single use di3posable module 634 and the multiple use module 650. As also described above, according to the illustrative embodiment, the single use module 634 includes all or substantially all ofthe perfusion fluid 108 contacting elements/assemblies ofthe system 100, along with s peripheral components, flow conduits, sensors and support electronics for Operating the blood ting components.

As sed above with reference to s 22A and 23D, according to the illustrative embodiment, the module 634 does not include a processor, instead relying on the controller 150, which may, for example, be distributed between the ?ont end interface circuit board 636, the power circuit board 720, the or interface module 146, and the main circuit board 718, for control. r, in other illustrative embodiments, the single use module 634 may include its own controller/processor, for example, on the ?oat end circuit board 637.

Referring to Figures 24A-280, the single use module 634 will next be described in terms of the ents included therein. After that, exemplary forward and retrograde ?ow modes are traced through the described components.

Referring ?rst to Figure 24A, the disposable module 634 includes a chassis 635 having upper 750a and lower 75% sections. The upper section 750a includes a platform 752 for supporting various components. The lower section 7501*: supports the platform 752 and includes structures for pivotably ting with the multiple use module 650. More particularly, the lower chassis section 75% includes the C—shaped mount 656 for rigidly mounting the sion ?uid pump interface assemblp 300, and the projection 662 for sliding into and snap ?tting with the slot 660 ofFigure 2013. The lower chassis section 75% also provides ures for mounting the oxygenator 114. As n Figures 25A and 25C, the lower section 750i) further includes structures for ng the heater assembly 1 10. Additionally, the reservoir 160 mounts to the underside of the platform 725 and extends into the lower s section 7501). Various sensors, such as the 02 saturation and hématocrit sensor 140 (shown in Figure 24A and described in detail below with reference to Figures 28A—28C), the ?ow rate sensor 136 (shown in Figure 24A), the ?ow rate sensor 138 (shown in Figure 258), are located within and/or mount to the lower chassis n 750i). The ?ow pressure compliance chamber 188 (shown in Figure 25B) is also d in the lower chassis section 75%. As shown in Figure 24D, the lower chassis section 750b also mounts the front end circuit board 637. ts located in the lower chassis section 75% are described in further detail below with reference to the normal and retrograde ?ow paths h the single use module 634. ing to Figures 24A~250, and as mentioned above, the upper chassis section 750a includes the platform 752. The platform 752 includes handles 752a and 75% formed therein to assist in installing and removing the single use module 634 from the multiple use module 650. Alternatively, such handles can be located on the platform 757 to allow for easier accessibility during installation ofthe single use module into the multiple use module. As shown most clearly in Figure 240, an angled platform 757 mounts onto the platfomi 752. The organ r assembly 104 mounts to the angled platform 757.

According to the illustrative embodiment, with the single use module 634 installed within the le use module 650, the platform 757 is angled at about 10° to about 80° relative to horizontal, to provide an optimal angle of operation for the heart 102 when placed within the organ chamber ly 104. In some illustrative embodiments, the platform 757 is angled at about 20° to about 60°, or about 30° to about 50° relative to horizontal.

The flow mode selector valve 112, the flow rate sensor 134, and the perfusion ?uid ?ow pressure compliance chambers 184 and 186 also mount onto the angled platform 757.

Referring to Figure 2413, l ?uid ports mount to the platform 752. For example, a ?uid sampling port 754 enables an operator to sample the ?ow into and/or out of the aorta 158 via the carmulation interface 162 on the organ chamber assembly 104. A ?uid sampling port 755 enables the operator to sample the flow into the left atrium 152 via the interface 170 on the organ chamber assembly 104. Additionally, a ?uid port 758 enables the operator to sample the coronary ?ow out ofthe pulmonary artery 164 via the pulmonary artery interface 166 on the organ chamber 104. According to the illustrative embodiment, the operator turns the a tive valve 754a, 755a or 758a to obtain ?ow from the sampling ports 754, 755 and 758. Flow from the particular port selected is provided at a single common outlet 764. According to one feature, only ?ow from the left most port selected is provided at the outlet 764. By way of e, if the operator opens both ports 755 and 758, only flow from port 755 is provided at the outlet 764. In this way, system 100 reduces the likelihood of an operator mixing samples from le ports.

The single use module 634 also includes a general injection port 762, le with the valve 762a, for enabling the operator to inject medication into the perfusion ?uid 108, for example, via the reservoir 160. Both the sampling 764 and injection 762 ports mount to the platform 752. Also d on the upper chassis section 750a is an infusion port 766, operable with the valve 766a, for ?owing the ional l 16 and preservative 118 ?uids into the perfusion ?uid 108. The upper chassis section 750a also includes a tube 774 for loading the exsanguinated blood from the donor into the reservoir 160. As shown in Figure 24D, the single use module 634 also includes non—vented caps 776 for ing vented caps on selected ?uid ports that are used while running a sterilization gas h the single use module 634 during sterilization. Preferably, such sterilization takes place prior to packaging the single use module 634 for sale.

The upper chassis section 7503. also includes the ?ow clamp 190 for regulating back pressure applied to the left ahium 152 when the heart 102 is cannulated and operating in nonnal ?ow mode in the organ chamber assembly 104. The upper chassis n 750a further includes a trickle valve 768. The trickle valve 768 may be opened and closed with the handle 768a to regulate a small ?uid ?ow to the left atrium 152 to moisten the lefc atrium 152 during retrograde ?ow mode. The upper chassis section 750a also includes ports 770 for infusion ofadditioual solutions and 772 for purging the oxygenator 114, operable with respective valves 770a and 772a.

As shown. most clearly in Figures 24A and 241), the upper chassis n 750 r includes the ?ow pressure probes 126, 128 and 130. As described above with nce to Figure l, the probe 126 es the pressure ofthe perfusion ?uid 108 ?owing into/out of the aorta 158. The probe 128 measures the pressure of the perfusion fluid 108 flowing into the le? atrium 152 through the pulmonary vein 168. The probe 130 measures the pressure ofthe perfusion ?uid 108 ?owing out of the pulmonary artery 164.

Each probe includes a respective tor 126a, 128a and 130a (shown ned for clarity) for coupling a respective signal 129, 131, and 133 to the front end t board 637.

Referring particularly to the single use module 654 cross-sectional side view of Figure 240, the reservoir 160 includes several components. More speci?cally, the reservoir 160 includes four inlets: 782, 784, 786 and 788. The inlet 782 transfers per?ision ?uid 108 from the drain 201 ofthe organ chamber 194 into the reservoir 160. The inlet 784 receives exsanguinated blood from the tube 774. The inlet 786 receives oxygenated perfusion ?uid 108 from the oxygenator 114, and the inlet 788 receives per?ision ?uid 108 out of the aorta 158 via the back pressure clamp 190. The reservoir 160 also has an outlet 790, which provides the perfusion ?uid to the one way inlet valve 191. The reservoir 160 ?rrther includes a defoamer 778 and a ?lter 780‘ The defoamer 778 removes bubbles out of the perfusion ?uid 108 as it enters the reservoir 160. According to the illustrative embodiment, the defoamer is made ofporous ethane foam with an am coating.

The ?lter 780 is a polyester felt, which ?lters debris, blood particles, emboli, and air bubbles out ofthe perfusion ?uid as it enters the reservoir 160.

As mentioned above in the summary, the 02 saturation and hematocrit sensor 140 employed in the single use module 634 includes important advantages over prior art approaches. Figures 28A—280 depict an rative embodiment of the 02 saturation and hematocrit sensor 140 of the ion. As shown in Figure 28A, the sensor 140 includes an" in-line cuvette shaped section oftube 812 connected to the conduit 798, which has at least one optically clear window through which an in?ated sensor can provide infrared light. ary sensors used in the in—line cuvetteshaped tube 812 are those made by Datamed, BLOP4. As shown in the cross—sectional view ofFigure 28B, the cuvette 812 is a one-piece molded part having connectors 801a and 80113. The connectors 801a and 8011) are con?gured to adjoin to connecting receptacles 803a and 803b, respectively, of conduit ends 798a and 7981). This interconnection between cuvette 812 and conduit ends 7988. and 79813 is con?gured so as to provide a substantially nt cross-sectional flow area inside t 798 and cuvette 812. The con?guration thereby reduces, and in Some embodiments ntially s, discontinuities at the interfaces 814a and 8141: between the cuvette 812 and the conduit 798. Reduction/removal of the discontinuities enables the blood based perfusion fluid 108 to ?ow through the cuvette with reduced lysing of red blood cells and reduced turbulence, which enables a more accurate reading of perfusion ?uid oxygen levels. This also reduces damage to the perfusion ?uid 108 by the system 100, which ultimately reduces damage done to the heart 102 While being perfused by the system 100.

According to the illustrative embodiment, the e 812 is formed from a light transmissive material, such as any suitable light transmissive glass or polymer. As shown in Figure 28A, the sensor 140 also es an optical transceiver 816 for directing light waves at perfusion ?uid 108 passing h the e 812 and for measuring light transmission and/or light re?ectance to determine the amount of oxygen in the perfusion fluid 108. As illustrated in Figure 28C, in some embodiments alight transmitter is located on one side of the cuvette 812 and a detector for measuring light transmission through the perfusion ?uid 108 is located on an opposite side ofthe cuvette 812. Figure 28C depicts a tOp cross-sectional View of the cuvette 812 and the transoeiver 816. The transceiver 816 ?ts around cuvette 812 such that transceiver interior ?at surfaces 811 and 813 mate t cuvette flat surfaces 821 and 823, respectively, while the interior conVex surface 815 of transceiver 816 mates with the cuvette 812 convex surface 819. In operation, when uv light is transmitted from the transceiver 816, it travels from ?at surface 811 h the ?uid 108 inside e 812, and is received by flat e 813. The flat surface 813 may be con?gured with a detector for measuring the light ission through the ?uid 108.

The ?uid flow path through the single use module 634 in both normal and retrograde flow modes will now be described with reference to Figures 24A—24D and Figure 25A. As described above with reference to s 1—4, the system 100 can maintain the heart 102 in two modes of Operation; 3 normal flow mode, shown in Figure 3, and a retrograde flow mode shown in Figure 4. As mentioned above with regard to Figure 1, to change betWeen normal and retrograde flow modes, the system 100 provides the ?ow mode selector valve 112, shown in detail in s 26A and 26B. To e in normal flow mode, the operator sets the ?ow mode selector valve handle 1126 to the on indicated in Figure 24A This has the effect of ng the ?ow paths through the selector valve 112 as shown in Figure 26A. Speci?cally, in normal flow mode, ?uid can ?ow into port 1 12b, through the ?ow channel 112fand out the port 1 120. Additionally, ?uid can ?ow into port 1 12d, through the ?ow channel 112g and out the port 112a. To operate in retrograde ?ow mode, the operator sets the ?ow mode selector valve handle 112e to the position indicated in Figure 248. This has the effect ofaligning the ?ow paths through the selector valve 112 as showu in Figure 26B. Speci?cally, in retrograde ?ow mode, ?uid can ?ow into port 112b, h the ?ow channel 11211 and out the port 112d.

Referring to Figure 24A, in normal ?ow mode, the reservoir 160 provides the perfusion ?uid 108 to the one way inlet valve 191 ofthe per?lsion pump interface assembly 300. Referring to Figure 25A, the perfusion pump 106 pumps the perfusion ?uid 108 out the outlet valve 310. Referring to Figure 250, the perfusion ?uid 108 then ?ows through the conduit 792. and the compliance chamber 138 and into the inlet 110a ofthe heater assembly 110. The heater assembly 110 heats the ion ?uid 108 and then ?ows it out the heater outlet 1101). Referring to Figure 24A, the heated perfusion ?uid 103 ?ows from the heater outlet 11% in the lower chassis section 75% through the chassis plate 752 and into the port 1121) of the mode select valve 112 via the conduit 794.

Referring also to Figure 24D, the perfusion fluid 108 ?ows out the mode valve port 1120, through the compliance chamber 186, the conduit 796, and the pressure sensor 128 into the pulmonary vein cannulation interface 1’70 on the organ chamber assembly 104. ing to Figure 24A, in nonnal ?ow mode, the heart 102 pumps the perfusion ?uid 108 out the pulmonary artery 164 through the pulmonary artery interface 166 and the pressure sensor 130. The conduit 796 then ?ows the perfusion ?uid 108 from the pulmonary artery interface 166 through the plate 752 and through the 02 saturation and hematocrit sensor 140. Referring also to Figures 25A and 25C, the conduit 798 then ?ows the perfusion ?uid 108 from the sensor 140 through the ?ow~rate sensor 136 into the oxygenator 114. The conduit 800 ?ows the per?rsion ?uid 108 from the oxygenator 114 back into the reservoir 160 by way ofthe reservoir inlet 7 86.

Referring to s 24A, 24D and 24B, in normal ?ow mode, the heart 102 also pumps the perfusion ?uid 108 out ofthe aorta 158 through the aorta interface 162 and the pressure sensor 126. The conduit 802 ?ows the perfusion ?uid 108 from the pressure sensor 126 through the ?ow rate sensor 134 and back into the port 112d on the ?ow mode selector valve 112. A clamp 804 holds the conduit 802 in place. A conduit 806 ?ows the perfusion ?uid 108 out the port 112a from the flow mode selector valve 112 through the compliance chamber 184 and the back pressure adjustment clamp 190. As mentioned above, the clamp 190 may be adjusted to restrict ?ow through the conduit 806 to adjust the back pressure seen by the aorta 158 during normal ?ow mode to more realistically te normal physiologic conditions. ‘Ihe compliance chamber 184, which can expand and contract as per?rsion ?uid 1081's pumped into and out of it, interoperates with the clamp 190 to dampen ?ow pressure Spikes to further improve tion of near~norma1 physiologic conditions. The a?er~load clamp 190 is con?gured to closely emulate systemic vascular resistance ofthe human body which a?‘ects aortic re, left atrial pressure, and coronary ?ow. A conduit 808 returns the perfusion ?uid 108 into the oir 160 by way of the reservoir inlet 788.

In rade ?ow mode, the ?ow mode selector valve 112 is oned as shown in Figure 24B. Referring to Figure 24B, the oir 160 provides the perfusion ?uid 108 to the inlet valve 191. As shown in Figure 25A, the perfusion pump 106 pumps the perfusion ?uid 108 out the outlet valve 310. As shown in Figure 250, the per?rsion ?uid 108 then ?ows through the conduit 792 and the compliance chamber 188 and into the inlet 110a of the heater assembly 110. The heater assembly 110 heats the perfusion ?uid 108 and then ?ows it out the heater outlet llOb. Referring to Figure 24B, the heated perfusion fluid 108 flows ?om the heater outlet 11013 in the lower chassis section 75013 through the chassis plate 752 and into the input 112b ofthe mode select valve 112 via the conduit 794.

Referring also to Figure 24]), the per?zsion ?uid 108 flows out the mode valve outlet 112d, into the conduit 802, through the flow rate sensor 134, the pressure sensor 126 and into the aorta 158 via the aorta ace 162. The perfusion ?uid 108 then ?ows through the coronary sinus 155 and the rest of the coronary vasculature.

Referring to Figure 24B, in retrograde ?ow mode, the heart 102 pumps the perfusion ?uid 108 out ofthe ary artery 164 and through the pulmonary artery interface 166 and the pressure sensor 130. The conduit 796 then ?ows the perfusion ?uid from the ary artery interface 166 through the plate 752 and into the 02 saturation and hematocrit sensor 140. Referring also to Figures 25A and 250, the conduit 798 then ?ows the perfusion fluid 108 from the sensor 140 through the ?ow rate sensor 136 into the ator 114. The conduit 800 ?ows the perfusion ?uid 108 from the oxygenator 114 back into the reservoir 160 by way ofthe reservoir inlet 786. In retrograde ?ow mode, substantially no perfusion ?uid is pumped into or out of the left atrium 152 via the pulmonary vein 168 and the pulmonary vein interface 170, with the exception of a small amount ofperfusion fluid diverted by the trickle valve 768 from the conduit 794 around the ?ow mode selector valve 112 into the compliance chamber 186. As ned above, the trickle ?ow provides suf?cient perfusion fluid 108 to keep the left atrium 152 moistened during retrograde ?ow.

As described above, the illustrative embodiment of the system 100 has one or more sensors or probes for measuring fluid ?ow and pressure. The probes andfor s may be obtained from standard cial sources. The ?ow rate sensors 134, 136 and 138 are conventional, ultrasonic ?ow sensors, such as those available from Transonic Systems Inc, Ithaca, NY. The fluid pressure probes 126, 128 and 130 may be tional, strain gauge pressure s available from MSI or GE. Thermometrics. Alternatively, a pre- calibrated pressure transducer chip can be embedded into organ chamber connectors and wired to a data collection site such as the front end board 637.

Having described the electrical and mechanical components and ?mctionality of illustrative embodiments ofthe system 100 and certain modes of operation thereof, the system 100 will next be bed with reference to the illustrative organ harvest and transplant procedures ofFigures 29A and 2913. More particularly, Figure 29A is a ?ow diagram 900 depicting exemplary methodologies for harvesting the donor heart 102 and ating it into the system 100 at a donor location. Figure 29B depicts particular points of care for handling the heart 102 in preparation for cannulation, and Figure 30 is a ?ow diagram 902 ofexemplary methodologies for removing the donor organ 102 from the system 100 and transplanting it into a patient at a recipient site.

As shown in Figure 29A, the process of obtaining and preparing the heart 102 for cannulution and ort begins by providing a suitable organ donor 904. The organ donor is brought to a donor location, pon the process of receiving and preparing the donor heart 102 for cannulation and transport ds down two intersecting pathways 906 and 908. The pathway 906 principally involves ing the donor heart 102 for transplant, while the pathway 908 principally involves preparing the system 100 to receive the donor heart 102 and then transporting the heart 102 via system 100 to the recipient site.

With particular reference to Figure 29A, the ?rst pathway 906 es exsanguinating the donor 910, arresting the donor heart 914, explanting the heart 916, and preparing the heart 102 for cannulation 918 into the system 100. In ular, in the exsanguination step 910, the donor’s blood is removed and set aside so it can he used to perfuse the heart 102 during preservation on the system 100. This step is performed by inserting a catheter into either the arterial or venous vasculatlne of the donor to allow the donor’s blood to ?ow out of the donor and be collected into a blood collection bag. The donor’s blood is allowed to flow out until the necessary amount of blood is ted, typically 1.0 — 2.5 , whereupon the catheter is removed. The blood extracted through exsanguination is then ?ltered and added to a fluid reservoir 160 of the system 100 in preparation for use with the system 100. Alternatively, the blood can he exsanguinated ?om the donor and ?ltered for leukocytes and platelets in a single step that uses an apparatus having a ?lter integrated with the cannula and blood collection bag. An example of such a ?lter is a Pall BCZB ?lter. After the donor’s blood is exsanguinated, the donor heart 102 is injected in step 914 with a cardioplegic solution to temporarily halt beating in preparation for harvesting the heart 102.

After the heart 102 is arrested, the heart 102 is explanted 916 from the donor and ed 91 B for loading onto the system 100. In general, the steps of explanting the heart 916 and preparing for loading 918 involve severing the connections n the vasculature ofthe heart 102 and the interior chest cavity ofthe donor, suturing various of the severed connections, then lifting the heart 1 02 from the chest cavity.

More particularly, as shown in Figure 2928, the right and left pulmonary arteries 164a and 164b are severed, and the right pulmonary artery 164a is tied~offby a surgical thread 901a or other suitable mechanism. The tying prevents ?uid from ?owing through the severed end 903a ofthe left pulmonary artery 164a. As described above with reference to s 24A~24B, the left pulmonary artery 1641) remains unsutured to allow it to be cannulated to the organ chamber assembly 104, thereby allowing perfusion ?uid 108 to ?ow h the left pulmonary arter 1641), h the pulmonary artery caruiulation interface 170, and back to the reservoir 160. The left pulmonary veins 168i) and 1691) and the right pulmonary veins 168a and 169a are also severed, and all except a single -69.. pulmonary vein 16% are tied offwith surgical thread 9011), 9010, and 901d, respectively.

This preVents ?uid from ?owing through the severed ends 903i) and 9035c of the right pulmonary veins 168a and 16951, or through the severed end 903d ofthe left pulmonary vein 168b, but allows the untied pulmonary vein to be cannulated to the organ r assembly 104 through the pulmonary vein interface 170. As described above with reference to Figures 24A-24B, this arrangement allows the perfusion ?uid 108 to ?ow through the right pulmonary artery 164b, h the pulmonary artery ace 166, and back to the oxygenator 114. Alternatively, blood can be expelled from the right ventricle via cannulating the pulmonary arterial trunk. The ary arterial trunk is not shown but includes the t of pulmonary artery 164 between the es 164a and 16413 of the pulmonary artery 164 and the right ventricle 159. The superior vena cava 161 is also severed and, once the heart is connected to the system 100 and begins beating, is tied with thread 90le to t ?uid from ?owing through its end 903e, The inferior vena cava 163 is similarly severed and tied with thread 901f or oversewn to prevent ?uid from ?owing through its end 903i The aorta 158 is also severed (in the illustrated embodiment at a point downstream from the coronary sinus 155) but is not tied off, allowing it to he ated to the organ chamber assembly 104. In one ment, the aorta 158 is ated to an aortic connector, which can be easily attached to the aorta interface 170.

With centinued reference to the ?ow chart of Figure 29A, after the heart vasculature is severed and appropriately tied, the heart 102 is then loaded onto the system 100 by inserting it into the organ r assembly 104 and cannulating the aorta 158, left pulmonary artery 164b, and a pulmonary vein 16933 to the appropriate points in the organ chamber assembly 104.

Often, hearts obtained from donors who have also donated their Iungs are missing part or all ofthe left atrium 152. In this situation, the heart 102 can still he instrumented and per?lsed in the retrograde mode by cannulating the aorta 158 and either the right pulmonary artery 164a or pulmonary artery trunk (not shown, but described above), and allowing any remaining left atrium 152 portion to remain open during the preservation period.

With continued reference to Figure 29A, during the preparation ofthe heart via path 906, the system 100 is prepared through the steps of path 908 so it is primed and waiting to receive the heart 102 for cannulation and transport as soon as the heart 102 is prepared. By quickly transferring the heart 102 from the donor to the system 100, and subsequently per?ising the heart 102 with the ion ?uid 108, a medical operator can minimize the amount oftime the heart 102 is deprived ofoxygen and other nutrients, and thus reduce ischemia and other ill effects that arise during current organ care techniques.

In certain embodiments, the amount of time between infusing the heart 102 with cardiOplegic solution and beginning flow of the perfusion ?uid 108 h the heart 102 Via the system 100 is less than about 15 minutes. In other illustrative embodiments, the between-time is less than about 1/2 hour, less than about 1 hour, less than about 2 hours, or even less than about 3 hours. Similarly, the time between transplanting the heart into an organ care system 100 and ng the heart 102 to a near logical temperature (e.g., lO between about 34° C and about 37° C) occurs within a briefperiod of time so as to reduce ischemia within the heart tissues. In some illustrative embodiments, the period of time is less than about 5 s, while in other applications it may be less than about 1/2 hour, less than about 1 hour, less than about 2 hours, or even less than about 3 hours. According to some illustrative ments, the heart can be transferred directly from the donor to the [5 system 100, t the use ofcardioplegia, and in such ations the time to beginning the flow ofwarm per?ision ?uid 108 and/or time to the heart reaching near physiologic temperature is similarly less than about 5 minutes, less than about Va hour, less than about 1 hour, less than about 2 hours, or even less than about 3 hours. In one implementation, the donor heart is not arrested prior to removal from the donor, and is instrumented onto the system 100 while the heart 102 is still beating.

As shown in Figure 29A, the system 100 is prepared in pathway 908 through a series of steps, which include preparing the single use module 634 (step 922), priming the system 100 with priming solution (step 924), ?ltering the blood from the donor and adding it to the system 100 reservoir 160 (step 912), and connecting the heart 102 into the system 100 (step 904). In particular, the step 922 ofpreparing the single use module 634 includes assembling the disposable single use module 634. Suitable assemblies are shown, for example, in Figures 24A-24D, Figures ZSA—ZSC, and Figure 26. After the module 634 is assembled, or provided in the riate assembly, it is then inserted into multiple use module 650 through the s described above with reference to Figures 21A-ZlC.

In step 924, the loaded system 100 is primed with priming solution, as described in more particular detail below with reference to Table 1. According to one feature, to aid in priming, the system 100 provides an organ bypass conduit 810 shown installed into the organ chamber assembly 104 in Figure 27A. As depicted, the bypass conduit includes three segments 810a~810c. Segment 810a attaches to the pulmonary artery cannulation interface 170. The segment 8101) es to the aorta cannulation interface 810b, and the segment 8100 attaches to the ary vein cannulation interface 166. Using the bypass conduit 810 so attached/cannulated into the organ chamber assembly 104, an Operator can cause the system 100 to ate the ion ?uid 108 through all of the paths used during actual operation. This enables the system 100 to be thoroughly tested and primed prior to cannulating the heart 102 into place.

In the next step 912, blood from the donor is ?ltered and added to the reservoir 160. The ?ltering process helps reduce the in?ammatory process through the complete or partial removal of leukocytes and platelets. Additionally, the donor blood is mixed with one or more nutritional 116 and/or preservative 118 solutions to form the perfusion ?uid 108. In step 926, the system 100 is primed with the perfusion fluid 108 by pumping it through the system 100 in the retrograde flow mode, as described above in reference to Figure 2413, and with the bypass conduit 810 in place. As the perfusion ?uid 108 circulates through the system 100 in priming step 926, it is warmed to the desired ature as it passes through heater assembly 110. The d ature range and g applications are described above in reference to Figures 6A through 6E, and in respect to Figure 13. In step 920, after the system 100 is primed with the perfusion ?uid 108, the bypass conduit 810 is removed, and the heart 102 is instrumented, as described above and shownin Figure 27B, onto the system 100.

After the heart 102 is mented onto the system 100, the pump 104 is activated and the flow mode valve 112 is positioned in retrograde flow mode ibed above with reference to Figures 1 and 4) to pump the perfusion fluid 108 in retrograde ?ow mode through the aorta into the vasculature of the heart 102. The pumping of the wane, oxygen and nutrient enriched perfusion ?uid 108 through the heart 102 allows the heart 102 to function ex vivo in a near normal physiologic state. In particular, the warm perfusion fluid 108 warms the heart 102 as it perfuses through it, which may cause the heart 102 to resume beating in its natural fashion. In some instances, it is desirable to assist the heart 102 in resuming its beating, which may be done by providing hand massage or a de?brillation signal 143 (shown in Figure 22153) to the heart 102. This may be done as bed alarm: with reference to the organ chamber assembly of Figures SA—SF and operator interface 146 ofFigures 17A~17.T.

After the heart is instrumented onto the system 100 at step 920, subsequent steps 928 and 930 allow the or to test the heart 102 and the system 100, and to evaluate their tive conditions. Illustratively, step 928 involves evaluating ECG signals 379 and 381 from the sensors 142 and 144 (positioned as shown in Figure 27A), reSpectively, as well as hematocrit 145 and oxygen saturation 141 levels ofthe perfusion ?uid 108 from the sensor 140. As further described in reference to Figure 12 and Figures 17A - 171, the operator can also monitor the ?uid ?ows, pressures, and temperatures ofthe system 100 while the heart 102 is cannulated. As described above with reference to Figures 513 and SF, the testing step 928 may also include having the Operator touch/examine the heart 102 by lifting an outer lid 196 ofthe organ chamber 104 and touching/examining the heart 102 indirectly through the ?exible membrane 198b. During the evaluation step 930, based on the data and other information obtained during testing 928, the operator determines whether and how to adjust the system 100 properties (e.g., ?uid flows, res, and temperatures), and whether to provide additional de?brillation, or other needed modes of treatment to the heart 102. The operator makes any such adjustments in step 932, then repeats steps 928 and 930 to t and re—evaluate the heart 102 and the system 100. In certain embodiments, the operator may also opt to perform surgical, therapeutic or other procedures on the heart 102 during the adjustment step 932. For example, the Operator can conduct an tion ofthe physiological ?tness of the heart, such as for example, performing an ultrasound or other imaging test, performing an echocardiogram or stic test on the heart, measuring arterial blood gas levels and other evaluative tests.

In another application, during or after step 932, the system 100 allows a l Operator to evaluate the organ for compatibility with an ed recipient after explantation but prior to implantation into the donor. For example, the operator can perform a Human Leukocyte Antigen (HLA) matching test on the organ while the organ is ated to the system 100. Such tests may e 12 hours or longer and are performed to ensure compatibility ofthe organ with the intended recipient. The vation of an organ using the system 100 described above may allow for preservation times in excess ofthe time needed to caniplete anHIA match, potentially resulting in improved post-transplant outcomes. In the BIA matching test example, the HLA test can be performed on the heart while a piesm'vation solution is pumping into the heart.

According to a further illustrative ment, after the heart is functioning as determined by the step 932, the operator can perform surgery on the heart or provide therapeutic or other treatment, such as immunosuppressive treatments, chemotherapy, genetic testing and therapies, or irradiation therapy. Because the system 100 allows the heart 102 to be perfused under near physiological temperature, fluid ?ow rate, and oxygen saturation levels, the heart 102 can be maintained after the adjustment step 932 for along U! period of time (e. g., for a period of at least 3 days or more, greater than at least 1 week, at least 3 weeks, or a month or more) to allow for repeated evaluation and ent.

According to the rative embodiment, the g 928, evaluation 930 and adjustment 932 steps may be ted with the system 100 operating in rade ?ow mode, or may he conducted with the system 100 operating in normal ?ow mode. In normal ?ow mode, the operator can test the function ofthe heart 102 under normal or near normal physiologic blood flow conditions. Based on the evaluation 930, the settings of the system 100 may be adjusted in step 932, ifnecessary, to modify the ?ow, heating and/or other characteristics to stabilize the heart 102 in step 934 in preparation for transport to the recipient site in step 936. After the heart 102 and the system 100 is tested and evaluated to ensure appropriate performance, the system 100 with the loaded heart 102 is transported to the recipient site at step 936.

Referring now to Figure 30, the ?rst phase 942 of the lant process involves repeating the testing 928 and evaluation 930 steps undertaken just prior to leaving the donor site 936. If the ?mction and characteristics ofthe heart 102 are not acceptable, the system 100 can be adjusted 942 as appropriate, for example, to provide appropriate ?uid oxygenation or ional levels, or to se or decrease the appmpriate ?uid temperature. As noted above, surgical and/or other therapeutic/remedial procedures may be performed on the heart 102, along with the testing 928 and evaluation 930. According to the illustrative embodiment, testing at the recipient site may be performed in retrograde flow mode, normal ?ow mode, or a combination ofhoth.

At step 946, after testing is complete, the system 100 is placed in normal/forward ?ow mode. In certain embodiments, this step 946 is not initiated until the le? atrium 152 and pulmonary vein 164 are cannulated, there is adequate operating volume in the system, the heart exhibits stable electrical activity, the ABG and electrolytes are within acceptable ranges, SVOZ is >80%, and blood temperature is between about 34°C and about 36°C. The step 946 is may be accomplished by slowing and/or stepping the retrograde g of the system 100, then restarting the pumping in d mode. In n embodiments, prior to restarting in d mode, the user opens the aortic sampling port 7543, releases the pressure control clamp 190 by turning it counterclockwise, then increases the ?ow rate ofpump 106 to about 1.0 lein, sets the ?ow control valve 112 to normal/forward ?ow, and increases the ?ow rate ofpump 106 to about 2.0 L/min to allow the blood 102 to disPlace air in the ate lines (e.g.,-802) of the system 100 and pass through the left side of the heart 102 and down the reservoir return line 808. The user then closes the aortic sampling port 754a.

The flow rate ofthe ion ?uid 108 emitted ?om the pump 106 is then increased at step 950 to a level ofthe clinician’s choosing ally between about 1 Lin-tin to about 5 L/min) to approximate the physiologic ?ow rate provided by the heart 102 while ?rnctioning in normal beating mode. The heart 102 and the system 100 are again tested at step 952 in a similar fashion to that described above With respect to steps 928 and 930. The ian may also choose to perform any other tests or evaluations on the heart, for example echocardiogram, electrolyte measurements, cardiac enzyme measurements, metabolyte measurements, intravascular ultrasound evaluation, pressure- volume loop evaluation, and Miller pressure evaluation.

In the third phase 946 at the recipient site, the heart 102 is prepared for implantation into the recipient. This phase includes the step 956 ofpowering down the pump 106 to stop the ?ow ofperfusion ?uid 108. Next, in step 958, the heart 102 is arrested, for example by injecting it with cardioplegic solution in a similar fashion to what is done in step 914 at the donor site. In step 960, the heart 102 is de-cannulated and removed from the organ chamber assembly 106. In step 962, the heart 102 is lanted into the recipient patient by ?rst removing the sutures 901a—901f, then ing the heart 102 into the recipient’s chest cavity, and suturing the various heart vesicles (e.g., 158, 164a, 164b, 168a, 168b, 169a, 169b, and 90321—9031) to their riate mating vesicles within the ent.

While external devices and methods have been described to de?brillate the head; deliver pacing signals to the heart, and perform blood chemistry analyses from samples taken from the perfusion ?uid, it may also be bene?cial to integrate these features into the portable system. Such features include de?brillation, pacing, diagnostic ECG sensing, and blood chemistry analyses.

As described above, the system 100 s a. priming solution, and also employs a perfusion ?uid 108 that combines a nutritional supplement 116 solution and a vative solution 11 8 with a blood product or tic blood product to form the perfusion ?uid 108. The priming, supplement 116, and preservative ll8solutions are described next.

According to certain ments, solutions with particular solutes and concentrations are selected and proportioued to enable the organ to function at physiologic or near physiologic conditions. For example, such conditions include maintaining organ function at or near a physiological temperature and/or preserving an organ in a state that permits normal cellular metabolism, such as protein synthesis.

In certain embodiments solutions are formed ?rom compositions by combining components with a fluid, ?om more concentrated solutions by dilution, or from more dilute solutions by concentration. In exemplary embodiments, suitable solutions include an energy source, one or more stimulants to assist the organ in continuing its normal physiologic function prior to and during transplantation, and one or more amino acids selected and proportioned so that the organ continues its ar metabolism during perfusion. Cellular metabolism includes, for example conducting protein synthesis while functioning during ion. Some illustrative solutions are aqueous based, while other rative solutions are non-aqueous, for example organic solvent-based, ionic-liquid— bascd, or fatty—acid-based.

The solutions may include one or more energy-rich components to assist the organ in conducting its normal physiologic function. These components may include energy rich materials that are metabolizable, and/or ents of such materials that an organ can use to size energy sources during per?isiOn. ary sources of energy-rich molecules include, for example, one or more carbohydrates. Examples of carbohydrates include monosaccharides, disaccharides, oligosaccharides, polysaccharides, or combinations thereof, or precursors or metabolites thereof. While not meant to be ng, examples ofmonosaccharides suitable for the solutions include s; heptoses; hexoses, such as fructose, allose, aliIose, e, mannose, gulose, idose, galactose, and talose; es such as ribose, ose, xylose, and lyxose; cs such as erythrosc and threose; and trioses such as glyceraldehyde. While not meant to be limiting, examples of disaccharides suitable for the solutions include (+)—maltose (4-0~(oa—D-glucopyranosyl)- ucopyranose), (+)—cellobiose (4a0-(B~D-glucopyranosyl)~D~glucopyranose), (+)~ e (4~O’(I3-D-galactopyranosyl)-BnD-glucopyranose), sucrose (2—O-(oc—D— yranosyl)-B-D—fructo?1ranoside). While not meant to be limiting, examples of polysaccharides le for the solutions include cellulose, starch, amylcse, amylopectin, sulfomucopolysaccharides (such as dermatane sulfate, chondroitin sulfate, sulodexide, mesoglycans, heparan sulfates, idosanes, heparins and heparinoids), and glycogen. In some ments, acharides, disaccharides, and polysaccharides of both aldoses, ketcses, or a combination fare used. One or more s, including enantiomers, diastereomers, and/or tautomers ofmonossacharides, disaccharides, and/or polysaccharides, including those described and not described herein, may be employed in the solutions described herein. In some embodiments, one or more monossacharides, disaccharides, and/or polysaccharides may have been chemically modi?ed, for example, by derivatization and/orprotection (with protecting groups) of one or more functional groups. In certain embodiments, carbohydrates, such as dextrose or other forms ofglucose are preferred.

Other possible energy sources e ine triphosphate (ATP), (so-enzyme A, te, ?avin adenine dinucleotide (FAD), thiamine pyrophosphate chloride (co- carboxylase), otinamide adenine dinucleotide (NAD), ?~nicotinamide adenine dinucleotide phosphate (NADPH), and phosphate derivatives ofnucleosides, i.e. nucleotides, including mono—, di—, and tn'~ phosphates (e.g., UTP, GTP, GDF, and UDP), mes, or other bio-molecules having similar cellular metabolic functions, and/or metabolites or precursors thereof. For e, phosphate derivatives of adenosine, guanosine, ine (5~Me-uridine), cytidine, and uridine, as well as other naturally and chemically modi?ed nucleosides are contemplated.

In certain embodiments, one or more carbohydrates is provided along with a phosphate source, such as a nucleotide. The carbohydrate helps enable the organ to produce ATP or other energy sources during perfusion. The phosphate source may be provided directly through ATP, ADP, AMP or other s. In other illustrative embodiments, a phosphate is provided through a phOSphate salt, such as glycemphosphate, sodium phOSphate or other phosphate ions. A phosphate may include any form thereofin any ionic state, including protonated forms and forms with one or more counter ions, The solutions may include one or more organ stimulants for assisting the organ’s normal logic function during ion. In some illustrative embodiments, where the transplanted organ is a heart, cardio stimulants are provided to enable the heart to continue functioning (e.g., continue beating) during perfusion and transplantation. Such stimulants may include, for example, catecholamines, such as epinephrine and/or norepinephn'ne, which facilitate beating of the heart. Other cardio stimulants may be used, such as certain forms ofpeptides and/or polypeptides (e.g., vasopressin, AnthropleurinnA and Antluopleu?n—B), and/or ?l/?zmadrenoreceptor blocking agents (such as CGP 12.177), buplinarol, pindolol, alprenolol, and cardiac glycosides. One or more natural products may also be used, such as digitalis (digoxin), palustrin, and/or ferulic acid.

Stimulants such as those mentioned above can be ed with the solutions or added at the point ofuse by the user.

In some instances, additional components are provided to assist the organ in conducting its metabolism during perfusion. These components include, for example, forms or tives of adenine and/or adenosine, which may be used for ATP synthesis, for maintaining elial function, and/or for attenuating ischemia and/or reperfusion injury. According to certain implementations, a ium ion source is provided with a phosphate, and in certain embodiments, with adenosine to further e ATP synthesis within the cells ofthe perihscd organ.

Solutions described herein may include one or more amino acids, preferably a ity of amino acids, to support protein synthesis by the organ’s cells. Suitable amino acids include, for example, any ofthe naturally-occurring amino acids. The amino acids may be, in various enantiomeric or diastereomeric forms. For example, solutions may employ either D- or L— amino acids, or a combination thereof, i.e. solutions euantioemiched in more‘of the D- or L- isomer or racemic solutions. Suitable amino acids may also be non-naturally occurring or modi?ed amino acids, such as citrullinc, orniithine, stein, homoserine, B—amino acids such as B-alanine, amino-caproic acid, or combinations thereof.

Certain exemplary solutions e some but not all natmallywccurring amino acids. In some embodiments, solutions include ial amino acids. For example, a on may be prepared with one or more or all of the following amino~acidsz His?dine Leucine ' Methionine _' Phenylalanine : . 1 com‘ne Tryptophan i Valine Lysine acetate In certain embodiments, non-essential and/or semi-essential amino acids are not included in the solutions. For example, in some embodiments, asParagine, ine, and/or cysteine are not included. In other embodiments, the solution contains one or more non-essential and/or semi-essential amino acids. Accordingly, in other embodiments, asparagine, glutamine, and/or cysteine are ed.

The ons may also contain electrolytes, particularly calcium ions for facilitating enzymatic reactions, cardiac contractility, and/or coagulation within the organ.

Other electrolytes may be used, such as sodium, ium, chloride, sulfate, magnesium and other inorganic and organic charged species, or combinations thereof. It should be noted that any ent provided der may be provided, where valence and stability pennit, in an ionic form, in a protonated or unprotonated form, in salt or fiee base form, or as ionic or covalent substituents in combination with other components that hydrolyze and make the component available in aqueous solutions, as suitable and appropriate.

In certain embodiments, the solutions contain buffering components. For example, suitable buffer systems include 2—morpholinoethanesulfonic acid drate (MES), cacodylio acid, HgCO3/N81'ICO3 (pKao, citric acid , bis(2-hydroxyethy1)—imino~ his-?iydroxymethyl)-mcthane (Bis-Tris), N—carbamoylmethylimidino acetic acid (ADA), 3»bis[nis(hydroxymethyl)rnethylamino]propane (Bis-Tris Propane) (pKal), piperazine—1,4~ bisCZ-ethanesulfonic acid) (PIPES), cctamido)aminoethanesulfonic acid (ACES), imidazole, N,N-bis(2—hydroxyethyl)-2—aminoethanesulfonic acid (BBS), 3-(N- morpholino)propanesulphonic acid (MOPS), NaHzPOdNaZI-IPO4 , N- ttis(hydroxymethyl)methyl—2—aminocthanesulfonic acid (TBS), N—(2~ltydroxyethyl)— piperazine-N‘ethane31dfonio acid (HEPES), N-(2-hydroxyethyl)piperazine-N‘-(2- ypropanesulfordc acid) (HEPPSO), tn'ethanolamine, N~ [tris(hydroxymethyl)methyllglycine (Tricine), tris hydroxymetirylaminoethane (Tris), glycineamide, N,N—bis(2~hydroxyethyl) e (Bicine), glycylglycine (pKaz), N- tris(hydroxymethyl)methyl~3~aminopropanesulfonic acid (TAPS), or a combination f. In some embodiments, the solutions n sodium bicarbonate, potassium phosphate, or TRIS buffer..

The solutions may include other components to help maintain the organ and protect it against ischemia, reper?ision injury and other ill effects during perfusion. In certain exemplary embodiments these components may e hormones (e.g., insulin), vitamins (e.g., an adult multi~vitamin, such as multi~vitamh1 MVI-Adult), and/or steroids (e.g., dexamethasone and SoluMedrol).

In another aspect, a blood product is provided with the solution to support the organ during metabolism. Exemplary le blood products may e whole blood, and/or one or more ents thereofsuch as blood serum, plasma, albumin, and red blood cells. In embodiments where whole blood is used, the blood may be passed through a leukocyte and platelet ing ?lter to reduce pyrogens, antibodies and/or other items that may cause in?ammation in the organ. Thus, in some embodiments, the on employs whole blood that has been at least partially depleted of leukocytes and!or Whole blood that has been at least partially depleted ofplatelets.

The solutions are preferably provided at a physiological temperature and maintained thereabout throughout perfusion and recirculation. As used herein, "physiological temperature" is referred to as temperatures between about 25°C and about 37°C, for example, between about 30°C and about 37°C, such as between about 34°C and about 37°C.

Table 1 sets forth components that are used in an exemplary aqueous priming solution. The component s in Table 1 are relative to each other and to the amount ofaqueous solvent employed in the solution (about 500 mL in the exemplary embodiment) and may be scaled as appropriate. In certain embodiments, the quantity of aqueous solvent varies i about 10%.

Table 1: Composition ofExamplary Priming Solution (about 500 mL aqueous solution) ent Specification Mannitol 12.5 g i about 10% . )l Sodium Chloride 4-8 g 153 about 10% 3 Potassium Chloride 185 mg :l: about 10% ~ _ l Magnesium Sulfate heptahydrate l :l: about 10% Sodium Glycerophosphate :1: about 10% The exemplary g solution is added to the system 100 through priming step 924, as more fully described with reference to Figure 29A.

With regard to the nutritional supplement solution 116, in certain embodiments it includes one or more carbohydrates and may also include a phosphate . The ional supplement solution 116 is lly maintained at apH of about 5.0 to about 6.5, for example about 5.5 to about 6.0.

Table 2 sets forth components that are used in an exemplary nutritional supplement solution 116. In some embodiments, the nutritional solution 116 further includes sodium glycerol phosphate. The amount of components in Table 2 is relative to the amount of aqueous solvent employed in the solution 116 (about 500 m1.) and may be scaled as appropriate. In some embodiments, the quantity of aqueous t varies i about 10%.

J Tale 2: Camponents ofExemplary Nutritional golution (about 500 mL) 7" Dextrose In certain embodiments the nutritional solution 116 es one or more carbohydrates and may also include a phosphate source. rI‘he nutritional on 116 is typically maintained at apI-I of about 5.0 to about 6.5, for example of about 5.5 to about The preservation solution 118 may include one or more preservatives. In an exemplary ment, one or more cardio stimulants are included for assisting normal physiologic function ofthe heart 102 during perfusion and transplantation. Such stimulants may include, for example, catecholamines, such as epinephrine and/or norepinephrine, which facilitate beating of the heart.

Other components may be added to the preservation solution 118, including, for e, adenosine, magnesium, ate, calcium, and/or sources thereof. In some instances, onal components are provided to assist the organ in conducting its metabolism during perfusion. These components include, for example, forms of adenosine, which may be used for ATP sis, for maintaining endothelial ?mction, and/or for attenuating ischemia and/or reperfusion injury. Components may also include other nucleosides, such as guanosine, thymidine (S-Me-uridine), cytidine, and uridine, as well as other naturally and chemically modi?ed nucleosides including nucleolides thereof.

According to some implementations, a magnesium ion source is provided with a phosphate source, and in certain ments, with adenosine to further enhance ATP synthesis within the cells of the perfused organ. A plurality o acids may also be added to support n synthesis by the heart’s 102 cells. Applicable amino acids may include, for example, any of the nahrrally—occuning amino acids, as well as those mentioned above.

Table 3 sets forth components that may be used in a solution 118 for preserving an organ as described herein. The solution 118 may e one or more of the components described in Table 3.

Table 3: Com mutant ofExem - Ia Com . osition for Prescrvative Solution Component Exemplary Concentration Ranges in Preservative ; Solution Alanine about 1 mg/L— about 10 glL , Ar'nine about 1 mg/L—about 10 1 a: e e,' . about 1 m L—about 10 ; As-artic Acid ' about 1 m_ L—about 10 _; L about I mg/L—about 10 L about I m_ L—about 10 L } Glutamic Acid about 1 mg/L— about 10 l _; I about I In —about 10 : i Glycine 1 EInr:e-:3a about 1 m- —about 10 1 J ‘ H drox oroline about 1 m L—about 10 ; l ‘ i about 1 mg/L—about 10 57‘I:0{3'G : about 1 mg/L—-about 10 g/L Lysine ’ about: 1 m 10 ' L Methionine E—_t - .I—iml , Sarina _ about 1 mg/L—about IO ; L Tr Aeolian about 1 m_ ~‘about 10 ; 'l'yrosine 1 about 1 m low-about lU L _ i Valine about 1 In —about 10 _ i u Adenine 1 about 1 m; ~about 10 L t , i>4ii about 10 ugIL—about 100 _ L : Adenylic Acid t about 10 ug/L — about 100 g/L . .32.. ; osition for Preservative Solution Component Exemplary Concentration Ranges in Preservative Solution about 10 u_ t 100 1 _about10uL—about100 : L Ascorbic Acid l about 1 u L ‘ — about 10 z—labout1uL~about10 L ,.

; Vitamin D~12 " about 1 ug/L— about 10 Cholesterol about 1 u_ —about 10 . ‘ _; L , Dextrose (Glucose) about 1 g/L — about 150 ; Multi-vitamin Adult — about 20 mg/L , about 1 mg/L or 1 unit vial r Eu-inehn'ne ‘ about] u_ —about1 - Folic Acid -about10 ; .

Glutathionc , ' about 1 u-about 1 ug/L— about 10 about 1 u -— about 10 31L : abouti - —about 100 L- about 10 ' L —about 10 z i —,Ml’—aboutlu Uracil ; about 1 m L- about 10 , .

E CaICium Chloride ;—_ about 1 mg/L ~about 100 g/L ; Ma- esium sulfate about 1 mg/L —about 100 g/L Potassium chloride about 1 m_ - about 100 o _ ' Sodium _l sewn-hoshatc about 1 mg/L -— about 100 ; Sodium Chloride about 1 m_ — about 100 1 Sodium Plies-hate ; Mi Insulin — Serum albumin -__' Pyruvate m about 1 ug/L-about 10g! _about 1 ml/L— about 100 ml/L Heparin ' about 500 UlL- about 1500 i ' U/L ; Solumedrol : about 200 mg/L—about 500 m L I ‘_about1m-m about 1 -. 1—.z ; _.-__L about 10 u- L — about 100 ;; L . GDP i about 10 u I rash" Table 4'sets forth components that are used in an ary vative solution 118. The amounts provided in Table 4 describe preferred amounts relative to other components in the table and may be scaled to e compositions of suf?cient quantity.

In some embodiments, the amounts listed in Table 4 can vary by 1 about 10% and still be used in the solutions bed herein.

Table 4: Components of Exemplary Preservative Solution ent Amount i Calcium Chloride dihydrate About 2100 mg - About 2600 mg L—AspartioAcid About 220 mg- About 270 mg - L—Glutamic Acid About 230 mg — About 290 mg —About200mg~About250mg —About100mgabout 130 mg About 300 mg — About 380 mg L-Methiouiue About 50 mg - About 65 mg —About45mg—About60mg ' About 110 mg~ About 140 mg mAbout80mg~About105mg §_About60mg—-About80mgll About 30 mg —— About 40 mg About 80 mg— About 110 mg About 150 mg~About 190 mg Acetate ‘ Lysine About 200 mg — About 250 mg —About350mg—About450mg _About15tug—About25mg t1500mgwAhoutzooo mg ' Dextrose About 25 gun—About 120 gm About 0.25 mg — About 1.0 mg About 75 Units - About 150 Units i SoluMedroi about 200 mg- 500mg ' Sodium onate About 10—25 mEq In the exemplary embodiment of a solution 118, the components in Table 4 are combined in the relative amounts listed n per about 1 L ofaqueous ?uid to form the solution 118. In some embodiments, the components in Table 4 are combined in the relative amounts listed therein per about 500 mL of aqueous ?uid and then combined with the solution 116, also about 500 mL, to provide a maintenance solution 116/118 of about 1 L ofaqueous ?uid. In some embodiments the quantity ofaqueous ?uid in ons 116, 118, and/or 116/118 can vary i about 10%. The pH ofthe solution 118 may be adjusted to be between about 7.0 and about 8.0, for e about 7.3 and about 7.6. The solution 1 18 may be sterilized, for example by autoclaving, to provide for improved purity.

Table 5 sets forth another ary preservative solution 118, comprising a tissue e media having the components identi?ed in Table 5 and combined with an aqueous ?uid, which may be used in the perfusion ?uid 108 as described herein. The amounts of components listed in Table 5 are relative to each other and to the quantity of aqueous on used. In some embodiments, about 500 mL of aqueous ?uid is used. In other embodiments about 1 L of aqueous fluid is used. For example, combination ofabout 500 mL ofpreservative solution 118 with 500 mL ofnutritional solution 116 affords a maintenance solution 116/118 ofabout 1 L. In some embodiments, the quantity of aqueous solution can vary i about 10%. The ent amounts and the quantity of aqueous sol??mlmlaimate for use. The pH ofthe preservative on 118, in this ment, may be adjusted to be about 7.0 to about 8.0, for example about 7.3 to about 7.6. i Table 5: Composition ofAnother Exemplary Preservative Solution (about 500 mL aqueous solution) ‘ Tissue Culture Component Speci?cation % Adenosine 750 mg 1 about 10% 2400 mg iabout10% L—Aspartic Acid L—Isoleucine -— L—Phenylalanine Table 5: Composition of r Exemplary Prescrvative Solution (about 500 mL aqueous solution) Tissue Culture Component } L—Proline _ : L-Ihereonine i about 10% L-Tryptophan l 35 mg i about 10% ‘ iL—Valine 171.5 mg iabout10% E Lysine Acetate 225 mg i about 10% Magnesium Sulfate Heptahydrate 400 mg i i about 10% ’ Potassium Chloride mg i about 10% Sodium de 1750 mg i about 10% - Since amino acids are the building blocks ofproteins, the unique characteristics of each amino acid impart certain important properties on a n such as the ability to provide structure and to catalyze biochemical ons. The selection and concentrations ofthe amino acids provided in the preservative solutions provide support ofnormal physiologic functions such as metabolism of sugars to provide energy, tion of protein metabolism, transport ofminerals, synthesis ofnucleic acids (DNA and RNA), regulation ofblood sugar and support ofelectrical activity, in addition to providing protein structure. Additionally, the trations of speci?c amino acids found in the preservative solutions can be used to predictably ize the pH of the maintenance solution 1 16/118 and ion ?uid 108.

Certain embodiments of the preservative solution 118 include epinephrine and a plurality of amino acids. In certain embodiments, the preservative solution 118 includes electrolytes, such as m and magnesium.

In one embodiment, a maintenance solution 116/118 is made from the combination ofthe preservative solution 118, including one or more amino acids, and the nutritional solution116, including one or more carbohydrates, such as e or dextrose. The maintenance solution 116/118 may also have additives, such as those described herein, administered at the point of use just prior to infusion into the organ perfusion system. For example, additional ves that can be included with the solution or added at the point of use by the user include hormones and steroids, such as dexamethasone and insulin, as well as vitamins, such as an adult multi—vitamin, for example adult itamins for infusion, such as MVI-Adult. Additional small molecules and large lecules may LII also be included with the solution or added at the point ofuse by the user at port 762, for example, therapeutics and/or components typically associated with blood or blood plasma, such as albumin.

In some embodiments, therapeutics that may be included in the itions, solutions, and systems described herein include hormones, such as thyroid es, for example T3 and/or T4 thyroid hormones. Further therapeutics that may be included include drugs such as anti—arrhytlunic drugs, for example, for heart therapy, and beta blockers. For instance, in certain embodiments, one or more thyroid hormones, one or more anti- arrhytlmiic drugs, and one or more beta blockers are added to the nutritional solution 116, the preservative on 118, and/or the maintenance solutions 116/118 either before or during perfusion of the organ. The above therapeutics may also be added directly to the system, for example, to the per'?lsion fluid 108, before or during perfusion of the organ.

With further reference to Table 4, certain components used in the exemplary preservation solution 118 are molecules, such as small organic les or large bio- molecules, that would be inactivated, for example through decomposition or denaturing, if 2O passed through sterilization. According to the system 100, the inactivatable components of the solution 118 may be prepared separately from the remaining ents of the solution 118. The te preparation involves separately ing each component through known techniques. The remaining components ofthe solution 118 are sterilized, for example through an autoclave, then combined with the biological components.

Table 6 lists certain biological components that may be separately puri?ed and added to the solutions described herein after sterilization, according to this two-step process. Those additional or supplemental components may be added to solutions 118, 1 16, l 1 6/1 18, the priming on or a combination thereof individually, in various combinations, all at once as a composition, or as a combined on. For example, in certain embodiments, the epinephrine, n, and MVI—Adult, listed in Table 6, are added to the nance solution 116/118. In another example, the SoluMedrol and the sodium bicarbonate, listed in Table 6, are added to the priming solution. The additional ents may also be combined in one or more combinations or all together and placed in on before being added to solutions 116, l 18, 116/l 18, and/or the g solution.

In some embodiments, the onal components are added directly to the perfusion ?uid 108 through port 762. The component amounts listed in Table 6 are relative to each other and/or to the amounts of components listed in one or more ofTables 1~5 as well as the amount ous solution used in preparing solutions 116, 118, 1 16/118, and/or the priming solution and may be scaled as appropriate for the amount of solution required.

Table 6: Exemplary Biological Components Added Prior to Use Speci?cation .

Catecholamine iabout 10% Hormone { Insulin about 100 Units Hormone iabout 10% ’ t MVI-Adult 1 mL unit vial Vitamin 3: about 10% SoluMedrol Sodium About 20 mEq & about 10% ‘ Bicarbonate In one embodiment, a composition for use in a maintenance solution 116/118 is provided comprising one or more carbohydrates, one or more organ stimulants, and a ity of amino acids that do not include asparagine, glutamine, or cysteine. The composition may also include other substances, such as those used in solutions described herein.

In another embodiment, a system for perfusing an organ, such as a heart, is provided comprising an organ and a substantially cell-free composition, comprising one or more carbohydrates, one or more organ stimulants, and a plurality ofamino acids that do not include asparagine, glutamine, or cysteine. Substantially cell-free includes systems that are substantially free ?om cellular matter; in particular, systems that are not derived from cells. For example, substantially cell-free includes compositions and solutions prepared from non-cellular sources.

In another aspect, the solutions 116 and 118 may be ed in the form of a kit that includes one or more organ maintenance solutions. An exemplary maintenance solution may include components identi?ed above in one or more ?uid solutions for use in an organ perfusion ?uid 108. In certain embodiments, the maintenance on 116/118 may include multiple ons, such as a preservation solution 118 and a nutritional on 116 and/or a mental composition or solution, or may include dry components that may be regenerated in a ?uid to form one or more solutions 116/ 1 18. The kit may also comprise components from the solutions 116 and/or 118 in one or more concentrated solutions which, on dilution, provide a vatiou, nutritional, and/or supplemental solution as described herein. The kit may also include a priming solution. In an exemplary embodiment, the maintenance solution includes a preservation solution 118 and a nutritional solution 116 such as those bed above, and a priming solution such as that described above.

In certain embodiments, the kit is provided in a single package, wherein the kit includes one or more solutions (or ents necessary to formulate the one or more solutions by mixing with an appropriate ?uid), and instructions for sterilization, flow and temperature control during perfusion and use and other information necessary or appropriate to apply the kit to organ perfusion. In certain embodiments, a kit is provided with only a single solution 116, 118 and/or 8 (or set of dry components for use in a solution upon mixing with an appropriate ?uid), and the single solution 116, 118 and/or 116/118 (or set of dry components) is provided along with a set of instructions and other ation or materials necessary or useful to operate the solution 116, 118 and/or 116/118 in the system 100.

In r aspect, the systems, solutions and methods may be used to r therapeutics to an organ during perfusion. For example, one or more ofthe solutions and/or systems described above may e one or more drugs, biologics, gene therapy vectors, or other therapeutics which are delivered to the organ during perfusion. Suitable exemplary therapeutics may include drugs, biologics, or both. Suitable drugs may include, for example, anti ?rngals, anti—microbials or anti-biotics, n?amatorles, anti» proliferatives, anti-Vitals, steroids, retinoids, NSAIDs, vitamin D3 and Vitamin D3 analogs, calcium channel blockers, complement neutralizers, ACE inhibitors, immuno- ssants, and other drugs. Suitable biologics may include proteins; suitable biologics may also include s loaded with one or more genes for gene therapy application.

For example, suitable steroids include but are not d to androgenic and estrogenic steroid hormones, androgen or antagonists and 5reductase inhibitors, and corticosteroids. Speci?c examples include but are not limited to alclometasone, clobetasol, ?uocinolone, fluocortolone, di?ucortolone, sone, halcinonide, mometasone, prednisone, prednisolone, methylprednisolone, triamcinolone, betamethasone, and dexamethasone, and various esters and acetonides thereof. le retinoids include but are not limited to retinol, retinal, isotretinoin, acitretin, adapalene, tazarotene, and bexarotene.

Suitable NSAIDs include but are not limited to naproxen, suprofen, ketoprofen, ibuprofen, ?urbiprofen, diclofenac, thacin, celecoxib, and xib.

Suitable vitamin D3 analogues include but are not limited to alcifercl, se‘ocalcitol, calcipotriene, tacalcito], calciuiol, ergocalciferol, and calcifediol.

Suitable iral agents include but are not limited to triiluridine, cidofovir, vir, penciclovir, famciclovir, valcyclovir, gancyelovir, and docosanol.

Suitable human carbonic anhydrase inhibitors include but are not limited to methazoliamidc, acetazolamide, and dorzolamide.

Suitable anti-proliferative agents include but are not limited to 548U, taxol, ubicin, and mitomycin.

Suitable antibiotic (antimicrobial) agents include but are not limited to bacitracin, chlorhexidine, chlorhexidine digluconate, ciproiloxacin, clindamycin, erythromycin,gentamicin, lome?oxaciu, metronidazole, minocycline, moxi?oxacin, mupirocin, neomycin, o?oxaein, polymyxin B, rifampicin, ru?ozacin, tetracycline, tobramycin, tn'closan, and vancomycin. The antiviral and cterial prodrugs described herein may be used to treat appropriately responsive systemic ions.

In certain embodiments, a solution system for use in a perfusion ?uid 108, sing a ?rst chamber ning a ?rst solution, such as a preservation solution 118, that es one or more cardio stimulants and a plurality of amino acids that do not include asparagine, glutamine, or cysteine, and a second chamber, containing a second solution, such as a nutIitional solution 116, that includes one or more carbohydrates, such as dextrose. The system may also include a ization system for izing the ?rst solution and the second solution prior to using the solutions to perfuse a heart. In some embodiments, one or more ofthe solutions 118 and 116 includes one or more therapeutics.

In some embodiments the solution system includes a third chamber comprising a priming solution, such as is described above, which may have one or more carbohydrates. In certain embodiments, the ?rst solution 118 includes epinephrine, adenosine, inSulin, One or more immuno-suppressants, a multi~vitamin, and/or one or more electrolytes.

Certain experimetal data are available to describe n embodiments ofthe ons described herein and their use in organ perfusion. Certain data are set for in Figures 31 ~33. Figure 31 depicts a chart demonstrating electrolyte stability for an organ under going perfusion in forward mode according to an embodiment of the system 100. In the embodiment associated with Figure 31, the organ is a heart 102 wherein perfusion is conducted in forward mode (as described above) by pumping perfusion ?uid 108 containing solution 116/1 18 to the let atria 152 and out of the aorta 158. The rate of perfusion is imately 30 mL/hr. As can be seen from Figure 31, the levels ofvarious electrolytes: sodium, potassium, calcium, and chloride ions, as well as dissolved glucose, remain at stable levels throughout the course ofperfusion, from before the organ is cannulated to the perfusion system 100 to six hours after eaunulation within the system Figure 32 depicts a chart demonstrating electrolyte stability for an organ under going retrograde perfusion ing to another embodiment ofthe system 100. In the embodiment associated with Figure 32, the organ is a heart wherein perfusion occurs by pumping the perfusion ?uid 108 containing the solution 116/118 into the aorta 158 and through the coronary sinus 155. The rate of perfusion is approximately 30 mL/hr. As can be seen from Figure 32, the levels ofvarious electrolytes: sodium, ium, calcium, and chloride ions, as well as ved e, remain at stable levels throughout the course of perfusion, from before the organ is emulated to the ion system 100 to six hours after cannulation. Figure 32 also demonstrates that the levels ofthe electrolytes and glncose remain at levels similar to those for the base line (BL) normal physiological state for the organ.

Figure 33 depicts a chart demoristiau'ng the arterial blood gas pro?le for an organ under going perfusion according to another embodiment of the invention. As can be seen from Figure 33, the levels of various blood : carbon dioxide and , and pH remain at stable leVels hout the six hour course ofperfusion. Figure 33 also demonstrates that the levels ofcarbon dioxide, oxygen, and pH remain at levels similar to those for two baseline (BL) measurements for the normal physiological state for the and methods to organ. Figures 31-33 demonstrate the ability of the present systems maintain an organ under stable physiological or near logical conditions.

It is to be understood that while the invention has been described in conjunction with the various rative embodiments, the forgoing description is intended to illustrate and not limit the scepe of the invention, which is de?ned by the scope ofthe appended claims. For example, a variety of systems and/or s may be implemented based on the disclosure and still fall within the scope ofthe invention. Other aspects, advantages, and modi?cations are within the scope ofthe following claims. All references cited herein are orated by reference in their entirety and made part of this application.

Claims

What we claim is:

1. A method comprising: placing an ex-vivo organ in a chamber of an organ care system; connecting the ex-vivo organ to a perfusion fluid circuit of the organ care system; opening an outer lid of the chamber of the organ care system; examining the ex-vivo organ through a flexible membrane of the organ care system; g, via the ion fluid circuit, a perfusion fluid to the ex-vivo organ; testing the ex-vivo organ or the organ care system; adjusting a setting of the organ care system in response to a result of the testing; and after adjusting the setting of the organ care system in response to the result of the testing, re-testing the ex-vivo organ or the organ care .

2. The method of claim 1, wherein the testing comprises measuring, with respect to the ex-vivo organ, an arterial blood gas level or a metabolite level.

3. The method of claim 1, wherein the g comprises measuring a flow rate of the perfusion fluid, a pressure of the perfusion fluid, or a temperature of the perfusion fluid.

4. The method of claim 3, wherein the measuring the pressure of the perfusion fluid comprises measuring, in a conduit, the pressure of the perfusion fluid flowing into the ex-vivo organ.

5. The method of claim 1, wherein the testing comprises ming, on the ex-vivo organ, a pressure volume loop evaluation.

6. The method of claim 1, wherein the adjusting the setting of the organ care system comprises selecting the setting of the organ care system from the group consisting of a flow rate of the perfusion fluid, a pressure of the ion fluid, a temperature of the perfusion fluid, an ation level of the perfusion fluid, and a nutritional level of the perfusion fluid.

7. The method of claim 1, wherein the adjusting the setting of the organ care system comprises applying, via one or more electrodes positioned between the ex-vivo organ and a pad in the organ care system, a defibrillation signal to the ex-vivo organ.

8. The method of claim 1, wherein the ex-vivo organ is an ex-vivo heart.

9. The method of claim 1, comprising: after the re-testing, evaluating the o organ for a compatibility with an intended recipient.

10. The method of claim 9, wherein the evaluating the ex-vivo organ for the compatibility with the ed recipient comprises performing, while the o organ is ted to the organ care system, a Human yte Antigen (HLA) ng test on the ex-vivo organ.

11. The method of claim 1, comprising: performing, while the ex-vivo organ is connected to the organ care system, a surgical procedure on the ex-vivo organ.

12. The method of claim 1, comprising: providing, to the ex-vivo organ, an suppressive treatment, a chemotherapy treatment, a genetic therapy, or an irradiation therapy.

13. The method of claim 1, comprising: after the adjusting the setting of the organ care system in response to the result of the testing, pumping the perfusion fluid in a retrograde flow direction.

14. The method of claim 1, comprising: slowing or stopping a retrograde flow of the perfusion fluid; and after slowing or stopping the retrograde flow of the perfusion fluid, pumping the perfusion fluid in a forward flow direction.

15. The method of claim 14, wherein the pumping the perfusion fluid in the forward flow direction comprises pumping the perfusion fluid in the forward flow direction at a flow rate n about 1 L/min and about 5.0 L/min.

16. A method according to claim 1, substantially as herein described with reference to any one or more of the examples or figures. ‘85 Nm?x muss— tom vill'l m9. 4?§*393P .93. o‘v’¢"¢'v‘i‘u‘q.$??%???iq "3:55 0 v n a...» ‘c~v . ‘ :‘H ‘ ' . '~:::I:~ 40.9..”‘9 itvvooo’o‘q O t C ‘ ¢ 9 v t I 4" IlkoootottC O Q C .900. 0 ‘~‘-t»:«:~;-:-;.:.;. 0.5.3.5.}; aavyvg* ~ 5? AA“. A3A)’ 03‘ 530$ OZ. .awmoI mEoE.