WO1988005261A1 - Systeme de perfusion totale pour organes - Google Patents

Systeme de perfusion totale pour organes Download PDF

Info

Publication number
WO1988005261A1
WO1988005261A1 PCT/US1988/000103 US8800103W WO8805261A1 WO 1988005261 A1 WO1988005261 A1 WO 1988005261A1 US 8800103 W US8800103 W US 8800103W WO 8805261 A1 WO8805261 A1 WO 8805261A1
Authority
WO
WIPO (PCT)
Prior art keywords
organ
emulsion
perfusion
primary
total
Prior art date
Application number
PCT/US1988/000103
Other languages
English (en)
Inventor
Donald R. Owen
Original Assignee
Tops Systems, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tops Systems, Inc. filed Critical Tops Systems, Inc.
Publication of WO1988005261A1 publication Critical patent/WO1988005261A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0236—Mechanical aspects
    • A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
    • A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts

Definitions

  • This invention relates to systems, including apparatus, fluid chemistries and procedures, for maintaining living biological organs or tissues.
  • the invention relates particularly to a total organ perfusion system that allows a donor organ to be maintained extracorporeally for an extended time period.
  • Pat. No. 3,660,241 disclosing an. organ chamber, and more particularly, an organ chamber that permits cannulation of an organ.
  • DeRoissart U.S. Pat. No. 3,772,153, discloses a refrigerated, pressurized environment for the perfusion of a living organ.
  • Bier U.S. Pat. No. 3,843,455, discloses a hypothermic perfusion system requiring heat exchange means.
  • Either the tissue metabolism may be reduced enough so that oxygen and energy carriers are unnecessary or one may attempt to meet as many of the requirements of normal metabolism as possible in the preservation setting.
  • the total organ perfusion system of the present invention instead uses an oxygen enriched emulsion as the oxygen-nutrient transport system to the organ interior.
  • This emulsion allows the organ to be maintained at higher temperatures, compared to previous systems, under the control of a series of sensing devices which enable the control of the chemical composition of the fluid.
  • the emulsion includes either a liquid fluorocarbon or porphyrin as active ingredients with micelles of less than 1 micron.
  • the total organ perfusion system of the present invention also permits the donor organ to be maintained over a broad range of temperatures as compared to previous systems.
  • Organs perfused with the apparatus, chemistries and methods of this invention may be changed between normothermic and hypothermic conditions without tissue degradation (ischemia).
  • the fluids used in this invention are high oxygen transference fluids. In many instances, these fluid compositions contain perfluorochemicals. Using the apparatus, chemistries and methods of this invention, it is possible to place a donor organ or tissue sample into virtually a state of suspended hibernation similar to the state that the organs of hibernating animals reach.
  • ATP adenosine tripnosphate
  • a total organ perfusion system includes an organ chamber for supporting an organ or other integrated tissue accumulation that has utility in the performance of bodily functions.
  • This organ chamber is supplied with an emulsion fluid or physiological electrolyte that is transported through a perfusion system.
  • the perfusion system both feeds the fluid into the organ interior and bathes the organ exterior.
  • a filtering system filters particulate waste, including bacteria and cellular debris, from the fluid that bathes and supplies nutrients to the organ.
  • This fluid is pumped through a transportation system, allowing particulate and toxic species to be removed from the fluid and allowing the fluid to be re-oxygenated prior to returning to the organ chamber.
  • the functional capability of the organ perfusion system of this invention requires the maintenance of a delicate balance between the chemistries of the perfusion fluids and the perfused organ.
  • the biological key to the successful maintenance of organs or tissue is the ability to maintain the correct electrolyte balance on either side of the cell membrane with a minimum of ATP usage by the organ or tissue.
  • the ultimate goal is to have cells, specifically heart tissue cells, optimized in their ability to produce contractions.
  • successful perfusion requires that sodium and calcium ions be kept outside the cell membrane and potassium within. This is a key element in maintaining low edema and low ATP usage by the sodium/potassium pump. It is essential that ion concentrations and thus electrolyte concentrations of sodium, potassium and calcium be maintained at appropriate levels.
  • the practice of the perfusion system of this invention enables the user to have extended time periods for the study of the physiology of tissue or organs. This will permit investigation of the intent of the organ and its performance. It will be possible to now measure the "performance" of organs under normothermic conditions. Practice of this invention permits study of organs and organ reactions in the "living state,” i.e., the state of full metabolic activity.
  • the method, chemistry and apparatus of this invention permit the repair of a donor organ while at normothermic temperatures. This will likely be a critical area for organ transplantation. This would be especially important if the particular organ being transplanted was one that is subject to tissue rejection.
  • Use of this invention will permit a diseased or otherwise malfunctioning organ to be surgically removed from a patient and cleansed, cured or otherwise modified extracorporally, and then surgically reimplanted in the same patient. The result of such a procedure would be elimination of rejection as an organ transplant problem.
  • the methods, chemistries and apparatus of this invention will further permit experimentation on drugs or therapeutic agents to identify their specific effects on isolated organs or tissues. Finally, and potentially most importantly, the methods, chemistries and apparatus of this invention will permit the low temperature oxygen starvation of organ or tissue to selectively kill diseased tissue which typically have an oxygen consumption rate significantly greater than that of normal tissue. This may be especially effective in the treatment of cancer.
  • two separate infusion media are employed. Each is circulated, filtered and oxygenated prior to infusion into the interior and around the exterior of the perfused organ within the organ support chamber.
  • One perfusion system utilizes a physiological electrolyte perfusate with levels of potassium allowing reduced sodium/potassium pump activity.
  • Another perfusion system utilizes a fluorocarbon or iron/magnesium porphyrin pseudoplasma emulsion as the oxygen nutrient transport system. The emulsions must be of a particle size below 0.2 microns to allow passage through the filter for bacterial removal.
  • a third and optional perfusion system is referred to as a shunted perfusion system which allows short-term perfusion of organs with heparinized whole blood for injury repair and preparation/conditioning of the organ prior to processing, i.e., medical research, transplantaion or the like.
  • the perfusion system is of critical importance to the practice of this invention.
  • the physiological electrolyte solution contains electrolytes, water soluble waste products, nutrients and proteinaceous species and is substantially filtered and dialyzed in the perfusion system.
  • a micro filter and hollow fiber dialyzer utilizing carbon and synthetic sorbants is used to remove toxic species prior to UV sterilization of the fluid.
  • composition used as a perfusion medium is a fluorocarbon/lipid hydrophobic emulsion.
  • This fluid is passed through a medium polarity grafted sorbant, thin film ultraviolet sterilizer, fluorocarbon to lipid analyzer, fluorocarbon/lipid addition and oxygenation cell and micro filtration cell prior to injection into the emulsifier.
  • the perfusion fluids of this invention contains no cellular components such as red blood cells, white blood cells, platelets, or the like, or immunoproteins, for example, Ig series or compliment.
  • the deemulsification system found in this perfusion system allows the hydrophilic and hydrophobic toxins to be removed separately utilizing the most efficient dialysis/sorbant technology.
  • Oxygenation of the perfusat ⁇ s can be accomplished directly by exposure to oxygen gas or by addition of peroxide to the fluid followed by ultraviolet exposure of the fluid in the oxygenation chamber.
  • fluorocarbon droplets stabilized by lipo proteins, can be viewed as artificial red blood cells.
  • the fluorocarbon droplets are "fouled” by hydrophobic toxins and lipids, the fluid is replaced.
  • Glucose, dextran, lipids, phospho-lipids and albumin are added as needed for nutrition, viscosity and osmotic pressure maintenance.
  • FIG. 1 is a schematic drawing of the specific components used in a preferred embodiment of the total organ perfusion system of this invention.
  • FIG. 2 is a schematic drawing of an embodiment of the refrigeration system that may be used in conjunction with the total organ perfusion system.
  • FIG. 3 is a schematic drawing of an embodiment of the oxygenation delivery system that may be used in conjunction with the total organ perfusion system.
  • FIG. 4 is a schematic drawing of an embodiment of the control system that may be used in conjunction with the total organ perfusion system.
  • FIG. 1, FIG. 2, FIG. 3 and FIG. 4 are schematic diagrams of a preferred embodiment of the present invention.
  • the total organ perfusion system of the present invention is used to maintain a human heart extracorporeally.
  • the system includes a heart chamber 1, which contains a polyurethane synthetic pericardial sac 2 in which the heart (not shown) is positioned.
  • the system has been designed such that the heart can be perfused in the heart chamber 1 from external fluid sources fed into, and removed from, the chamber by 12 volt D.C. gear pumps.
  • the described system incorporates two independent fluid sources, each of which includes two reservoirs.
  • this apparatus is capable of maintaining and perfusing the heart with either a physiological perfusate solution (secondary electrolyte solutions) or the aforementioned fluorocarbon pseudoplasma perfusate (primary emulsion).
  • a perfusate solution can either be fed into the heart chamber 1, to perfuse the organ, or recirculated between the two described reservoirs.
  • each of the perfusate solutions is maintained at preset pH, temperature, and oxygen concentration levels.
  • Perfusate solution pumped into the heart chamber perfuses the heart by entering the organ via a catheter positioned in the aorta through a branch artery. This configuration permits retro-perfusion of the coronary arteries which exits fluid into the right ventricle. Fluid in the right ventricle egresses through the surgically exposed main vessel orifices and into the pericardial sac 2.
  • Recirculation of a physiological electrolyte perfusate is performed in a fluid circuit comprising reservoir 4, membrane oxygenator 9, pH sensor module 15, and hydrostatic reservoir 7. Recirculation is affected by pump 18 which withdraws fluid from the bottom of reservoir 4, pumps it through the membrane oxygenator 9, whece the perfusate is oxygenated, and is finally pumped into the hydrostatic reservoir 7. Recirculation valves 24 and 27 are positioned such that fluid exiting this reservoir, through either the bottom port 35 or overflow port 34, returns back to reservoir 4 via lines 39 and 41. A small quantity of fluid diverted from line 42 is pumped through pH sensor module 15 by regulating manual valve 28.
  • Recirculation of fluorocarbon emulsion involves the transport of fluid from reservoir 3 to the thermal regulator/debubbler 5, via membrane oxygenator 8, by action of pump 19.
  • Level detector 44 regulates the amount of fluid that pump 19 charges into the debubbler by turning the pump on and off. Fluid from the debubbler is infused into hydrostatic reservoir 6 by pump 20.
  • Recirculation valves 25 and 26 are positioned such that fluid exiting the hydrostatic reservoir 6, through ports 32 and 33, is returned to reservoir 3. In addition to this fluid routing, a small quantity of the emulsion is circulated through pH sensor module 14 by pump 21.
  • Perfusion of the explanted heart in the heart chamber 1 by one of the perfusates is performed by re-directing recirculating fluid, exiting a hydrostatic reservoir, into the main perfusion inlet line 29 and the pericardial sac inlet line 38.
  • manual valves 25 and 26, in addition to solenoid valves 22 and 23, must be switched such that fluid egressing from hydrostatic reservoir 6, through ports 33 and 32, feeds into lines 38 and 30.
  • Lines 30 and 29 must be manually connected in order to permit the transport of emulsion into the heart via the flowmeter 36 and the arterial catheter 37.
  • perfusate also enters the heart chamber 1 through the bottom of the pericardial sac 2 by way of line 38.
  • This fluid bathes the exterior of the organ and mixes with the solution exiting from the right side of the heart.
  • This fluid then overflows from the pericardial sac 2, collecting at the bottom of the heart chamber 1, before being removed by pump 17.
  • Pump 17 draws fluid from the heart chamber 1 through filter 16 and pumps it back to reservoir 3 via filters 12 and 13. This completes a closed loop perfusion circuit.
  • FIG. 2 describes the cooling/heating circuits incorporated in the total organ perfusion chamber and interfaced to external refrigeration units.
  • FIG. 3 describes the gasification system of the total organ perfusion system.
  • Oxygenation and stabilization of the fluid pH is provided by 100% oxygen and 95% oxygen/5% carbon dioxide transferred to the electrolyte and emulsion perfusates in the membrane oxygenators 9 and 8, respectively.
  • the introducton of the oxygen/carbon dioxide gas mixtures is capable of reducing high solution pH when fed into the membrane oxygenators.
  • Separate pHcontrol circuits for each perfusate solution are utilized to control solenoid valves 46 and 47, which direct either oxygen or the oxygen/carbon dioxide gas mixture into the membrane oxygenators, depending on the pH of the solution. For instance, if the electrolyte perfusate pH were to rise above 7.7, solenoid valve 46 would be activated, causing the introductin of carbon dioxide/oxygen into the membrane oxygenator.
  • FIG. 4 describes the control systems incorporated in the described TOPS Mother Unit design. Control systems are employed to control: (1) level of fluid in the debubbler/oxygenator module 5, (2) pH of the fluorocarbon emulsion perfusate, (3) pH of the electrolyte perfusate, (4) temperature of fluorocarbon emulsion perfusate, and (5) pressure of perfusate introduced to the coronary vessels of the perfused heart.
  • the fluid level of perfusate in the debubbler/thermal regulator unit 5 is controlled by level detector 44 which shuts off pump 19 when a threshold level is achieved.
  • the level detector is based on the interruption of an IR beam, between an IR-emitting LED and an IR-detecting phototransistor, by a float which ascends/descends with varying fluid levels.
  • the pH of emulsion perfusate is detected by the emulsion pH sensor module 14, from which a signal is sent to the pH sensor (emulsion) (not shown).
  • This module activates/deactivates solenoid valve 47 when the high and low setpoints on this controller are reached. These setpoints are manually set by the operator.
  • a similar control system is employed to activate/deactivate valve 46 for pH detected in the electrolyte perfusate by the pH sensor in pH sensor module 15.
  • a temperture control system is incorporated into the heating/cooling system for the emulsion (described in FIG. 3).
  • An RTD temperature element 50 positioned in the hydrostatic reservoir 6, sends a signal to a temperature controller (not shown) which activates solenoid valve 45 when the emulsion temperature exceeds 37°C. This causes cooling fluid to circulate in the coil in 6.
  • a pressure release control system has bee.n incorporated into the emulsion fluid delivery system.
  • Pressure signals detected by the transducer 48 are sensed by a pressure controller (not shown). Should the pressure of the perfusate in the perfusion line 51 exceed a preestablished level, the pressure controller activates solenoid valve 49, which releases the back pressure in the hydrostatic reservoir 6, which rapidly decreases the pressure in the hydrostatic reservoir 6, and in turn, inside the heart.
  • Sensors may be placed in several locations in the system, allowing the instantaneous measurement of temperature, pH, and pO 2 of the perfusion medium. Such instantaneous measurement of these parameters may be important, because the proper maintenance of these parameters within specific ranges could be critical to the long-term survival of the heart tissue.
  • Included in this embodiment of the total organ perfusion system preferably is a conventional heart pacing mechanism used to induce and maintain a continuous steady heartbeat during normothermic testing to ensure that the heart has been maintained in a viable, transplantable condition.
  • the heart beats without pacer stimulation during normothermic testing.
  • the heart chamber preferably is a 4-1/2 gallon Nalgene polycarbonate tank (Cole-Parmer Instrument Company, Cat. No. R-6761-07).
  • Reservoirs 3 and 4 preferably are 1/2 gallon Nalgene polycarbonate tanks (Cole-Parmer Instrument Company, Cat. No. TV-6751-20).
  • Hydrostatic reservoirs 6 and 7 are preferably 1/4 gallon Nalgene polycarbonate tanks (Cole- Parmer Instrument Company, Cat. No. R-6761-15).
  • the cardiac catheters that may be used are conventional (USCI Extracorporeal Circulation Cannulae, Ve ⁇ nous Catheter, Cat. No. 007208).
  • the pumps 18-20 used in the system may include miniature 12 VDC gear pumps (Cole-Parmer Instrument Company. Part #R-7009-50).
  • Pumo 17 is preferably an Ismatec gear pump (Cole-Parmer Instrument Company Part #J-7617-75).
  • the solenoid valves preferably are 3-way plastic body solenoids (Automatic Switch Company, Model #8360A74).
  • the level detectors are preferably a lab assembled fiber optics interfaced photodiode/photodetector control system that includes a IR photodiode/photodetector set (Radio Shack, Cat. No. 276-225). This system may be assembled with a relay circuit board.
  • Temperature sensor 50 is preferably a platinum resistance thermometer (Omega Engineering, ITT-100, Model #G12-30).
  • the controller used to transform signals from the temperature sensors to signals to the solenoid valves is also conventional (Omega Engineering RTD Digital Controller, Model #4204-PF2-T).
  • the pH sensors are conventional ( Cole-Parmer Ins trument Company , Digi-sense pH Meter, Cat. No. BA-
  • a pO 2 sensor (not shown) preferably includes an oxygen probe (Cole-Parmer Instrument Company, Cat. No. R- 5948-52) and an oxygen meter (Cole-Parmer Instrument Company, Cat. No. R-5948-50).
  • Pressure gauges 52 and 53 are preferably 0-5 psi pressure gauges (Marsh Instrument Company). Pressure transducers 48 and 51 are also easily obtained (Omega
  • Particulate filters 10-13 are commercially available for use in the present system (Millipak 50, Millipore Products; Ultipor Filter Assembly, VWR Scientific).
  • the assorted valves and tubing used in this system are conventionally available; silicon and polyethylene tubing is preferred.
  • the membrane oxygenator is conventional (Scimed Life Systems, Model No. 0400-2A).
  • the cardiac pacemaker, thermal regulator debubbler and sensor module may be fabricated by those skilled in the art for use with a particularly designed system.
  • the apparatus of this invention and hypothermic conditions created by the apparatus are important elements of the preservation goals of this invention, the chemistries of the fluids circulating through the organs or tissue are likewise essential.
  • the control of electrolyte concentrations at membrane wall interfaces is an essential function of the solutions flowing through the apparatus and contained organ.
  • the ions that need to be controlled include, but are not limited to, chloride, sodium, potassium, calcium, magnesium, and phosphates.
  • a potential difference which is the direct result of ATP consumption.
  • a perfusion system which injects, fluids throughout the interior of the organ via cannulation devices and a perfusion system which circulates fluids on the outside of the organ.
  • a perfusion system which injects, fluids throughout the interior of the organ via cannulation devices and a perfusion system which circulates fluids on the outside of the organ.
  • maintaining the separation between an interior and exterior fluid is difficult due to leakage in the hardware associated with the system as well as leakage from the interior to the exterior of the organ itself, i.e., via surgical sutures and the like. Therefore, in a second preferred embodiment of the invention, the same perfusion fluid is circulated both externally and internally to the organ.
  • the primary perfusion emulsion is intended to provide virtually the same body functions as whole blood.
  • a commercially available primary perfusion emulsion material is manufactured by the Green Cross Corporation of Japan and is identified as FC-43 Emulsion.
  • the FC-43 emulsion is a perfluorochemical artificial blood, which is advertised as having utility for experimental studies in physiology, biology, biochemistry, chemotherapy, toxicology and metabolism studies.
  • the primary perfusion fluid is required to transfer oxygen and other biological nutrients to organ tissue. Therefore, oxygen must be soluble in at least one of the components of the primary perfusion emulsion.
  • One such family of material that has achieved commercial significance is generally identified as perfluorochemicals. Oxygen is highly soluble in liquid perfluorochemicals. Whereas normal saline or blood plasma dissolves about 3% oxygen (by volume) and whole blood about 20%, pure perfluorochemicals dissolve 40% or more.
  • Another parameter that is essential in the design of the primary perfusion emulsion is the size of particles present in such an emulsified solution. Particles larger than erythrocytes, which are about 7-10 microns in diameter, will not pass through small capillaries and thus increase the risk of embolism. It is therefore important that the primary perfusion emulsion have an average particle size which is appropriate for use in a capillary system and which will maintain the oxygen transfer function of whole blood for an indefinite period of time.
  • the component materials include oxygen exchange and transport chemicals, i.e., perfluorochemicals, and at the same time, be suitable for transport in the capillary system of the organ or tissue being perfused. It is also essential that the primary perfusion emulsion not be toxic to the organ or tissue nor have any deleterious side effects.
  • the secondary perfusion fluid includes an extra cellular electrolyte solution, an intracellular electrolyte solution, an intermediate solution and a transfer solution. Depending on the particular organ or hardware configuration, one or more of the secondary perfusion solutions may be omitted.
  • Secondary perfusion fluids are used to supplement the primary perfusion emulsion to achieve a specific effect.
  • the secondary perfusion fluids described in this application are meant primarily for the preservation of a heart organ or heart tissue. Therefore it is important that contractions and expansions of the heart muscle be controlled.
  • the extracellular electrolyte solution is used to control the electrolyte concentrations at the cell membranes in the heart.
  • a typical formula for the extracellular electrolyte solution is found in Table I herein below.
  • the heart By increasing the sodium ion concentration through infusion of the extracellular electrolyte solution into the primary perfusion emulsion, the heart can be frozen in contraction.
  • the intracellular electrolyte solution functions in much the same way as the external solution, although it is important that the electrolyte materials internal to the system also maintain the electrolyte charge across the cell membrane within acceptable parameters.
  • a typical composition for the intracellular electrolyte solution is found in Table II:
  • the hypothermic cell membrane potential can be maintained.
  • the intermediate secondary perfusion solution is described sometimes as a Krebs solution or a cardiopiegic solution.
  • the intermediate solution is an organ stopper in which the organ is stopped, but not frozen.
  • the primary function of the intermediate solution is to increase the sodium ion concentration in relationship to the potassium ion concentration.
  • the transfer solution is typically the same as the extracellular electrolyte solution with more calcium ion. The transfer solution is used during transfer of the organ or tissue.
  • the variables that must be maintained and monitored are pH, temperature, oxygen partial pressure and fluid pressure. Acceptable ranges for the heart organ for each of these variables are:
  • the method of this invention is very important, but is specific to each type of organ or tissue sample that is to be maintained or perfused.
  • the method will be described in terms of the steps and procedures necessary to perfuse and maintain a heart. This basic procedure may be modified to permit maintenance or perfusion of other organs or tissues.
  • the description of the method of this invention in conjunction with the maintenance/perfusion of a heart is not intended to be limiting on the scope of this invention, but merely exemplary of the procedures which are characteristic of use of the apparatus and chemistries of this invention.
  • the pumps, solenoid valves, level controllers and refrigeration units are checked for functional characteristics.
  • the sensors and controllers are then checked to verify that temperatures, pH, pressure transducers and radiometer oxygen partial pressure and carbon dioxide partial pressures are accurately measured and calibrated.
  • the perfusate systems are also checked for component concentrations.
  • the primary perfusion emulsion such as the FC-43 solution disclosed earlier, is prepared immediately prior to use by mixing the two electrolyte solutions with the pre-mixed emulsion.
  • the resulting emulsion is then charged into the reservoir of the perfusion system.
  • the temperature, pressure, flow rate and pH of the primary emulsion system are stabilized in the perfusion unit.
  • a cardioplegia solution is administered. This solution consists of about 15-18 miiiiequivalents of potassium ion.
  • the solution is administered to the heart via cannulation of the brachial artery.
  • the main vessels are ligated and the organ is immersed in a saline/icewater bath to bring the temperature to 4°C. The temperature is decreased so the oxygen consumption is minimized.
  • Perfusion with the 4°C cardioplegia solution is initiated in conjunction with the primary perfusion emulsion. It is essential that there be no leakage in the aortic valve or aorta itself and therefore, the coronary perfusion pressure and the resultant coronary flow are checked. An approximate flow of 25-35 milliliters per minute per 10 millimeters of mercury pressure should be anticipated.
  • an empty balloon is inserted from the apex of the heart into the left ventricle. The balloon is then blown up by a syringe with water.
  • the flow rate of the primary emulsion fluid into the heart chamber is adjusted to 50 milliliters per minute.
  • the arterial perfusion catheter is connected to the emulsion outflow tube. It is essential that bubble entrapment be avoided at the connection interface.
  • the emulsion to be delivered to the heart is stabilized at a temperature of 37°C ⁇ 1/2°; a pH of 7.4 + .05 and a pressure of 100 millimeters of mercury; and a flow rate of 150-250 milliliters per minute. The flow rate is dependent upon the coronary resistance.
  • Two pacemaker electrodes are sewn into the ventricular myocardium. Pacing with the custom pacer is set at 100 beats per minute, pulse width of 1.5 milliseconds and an amplitude of 5 volts.
  • the left ventricle balloon volume is increased until an end diastolic pressure (EDP) of 4 millimeters of mercury is attained. After 10 to 15 minutes of stabilization period, measurements from the left ventricle systolic pressure (SP) and EDP are recorded. Data for a complete pressure-volume curve (Starling's curve) are obtained by incrementing the balloon volume and recording the resultant ventricular SP and EDP for each increment. This pre-ssure volume serves as a control curve for heart function.
  • EDP end diastolic pressure
  • heart pacing is stopped, and the balloon is removed from the ventricle.
  • the emulsion solution is drained from the perfusion system, the refrigeration units are set to 0oC, and the cardioplegia solution is charged into the unit containing the heart.
  • the cardioplegia solution is stabilized in the unit at 5°C + 1°C, intraventricular pressure of 20 millimeters of mercury ⁇ 5 millimeters of mercury, a pH of 7.6 + 1, and a flow rate of 70 milliliters per minute + 10 milliliters per minute.
  • the heart With the perfusion system in place, the heart can be maintained indefinitely. It is likewise possible to raise the temperature of the heart if there is ATP depletion (which occurs more readily at low temperatures) and the ATP can be replenished and the heart temperature then regulated to its low oxygen consumption level.
  • Example 1 In this example, a dog heart is surgically isolated and maintained in the perfusion system. In the preparation system, the blood is removed from the dog and the normal blood volume is maintained by a rapid infusionof lactate or Ringer solution. The pericardium of the dog is opened, and standard surgical procedures are used to remove and isolate the heart.
  • the surgical procedure involves exposing the superior vena cava and inferior vena cava, suspending the pericardium with 2-0 silk suture, isolating the inferior vena cava and leave, as long as possible, a stalk of interior vena cava.
  • Heavy silks are passed around the superior vena cava and around the azygous vein.
  • the main pulmonary artery and ascending aorta are dissected free.
  • the inominate and left carotid arteries are dissected.
  • the animal is hepar-inized with 3 milliliters per kilo of heparin directly into the superior vena cava.
  • the superior vena cava is tied off together with the azygous vein.
  • the left common carotid is dissected and tied off and the proximal common carotid is clamped and a cannula is inserted into the ascending aorta.
  • the heart is allowed to beat several times so that the coronary return will pass through the lungs and will clear the blood from the lungs and the left heart.
  • the aorta is clamped and the heart is surgically removed by transecting the pulmonary veins, the aorta distal to a clamp and large vessels.
  • the heart is explanted at the same time that the cardioplegia solution is administered and the heart is then submerged in iced saline solution.
  • the heart is then inserted into the heart chamber and the cannula are connected to the perfusion system.
  • the perfusion system begins with a constant monitoring of pressure, pH, oxygen partial pressure and electrolytic concentrations.
  • the heart is removed and an autopsy is conducted.
  • the autopsy results indicate that at least 90% of the tissue in the heart has maintained viability.
  • Example 1 Circulation of perfusate through the surgically removed heart is performed in a closed loop wherein the solution is cooled and filtered. Fluid is then passed to a thermal regulator/debubbler via a membrane oxygenator where it is oxygenated with either 100% oxygen or 95% oxygen and 5% carbon dioxide. A portion of the perfusate in the thermal regulator unit is circulated through the pH sensor module to detect solution pH changes. From the thermal regulator/debubbler, the solution is pumped into the hydrostatic reservoir.
  • the hydrostatic reservoir is designed to provide passive perfusate pressure to the heart in the event of pump failure.
  • An overflow port on the reservoir prevents excess pressure buildup in the vessel and heart. The fluid passing through the port is directed into the base of the paracardial sac where the heart is suspended.
  • Pressurized flow from the hydrostatic chamber is directed through a 0-200 milliliter per minute rotameter, a 25 micrometer bubble trap and finally into the heart via a standard USCI arterial catheter.
  • Perfusate exiting the right ventricle fills the top of the pericardial sac and is collected on the bottom of the heart chamber.
  • a recirculation loop is completed by pumping the fluid in the heart chamber back to the reservoir.
  • the perfusate pH is stabilized between 7.4 and 7.8 by intermittent gasification of the solution with a 95% oxygen/5% carbon dioxide mixture in the membrane oxygenator.
  • a pH controller module detects pH variations by an electrode positioned in the pH sensor module. Values of pH above a threshold setting of 7.8 on the controller causes the module relay to activate a solenoid which then directs the membrane oxygenator inlet gas from 100% oxygen to 95% oxygen/5% carbon dioxide.
  • the formation of carbonic acid in the perfusate, generated by carbon dioxide acts to decrease the pH. Since the perfusate pH normally rises during these experiments, due to release of dissolved carbon dioxide, there is no need to increase the pH by addition of aqueous bases or the like.
  • Example 2 The autopsy on the dog heart perfused and maintained in Example 2 revealed that ischemic changes were minimized and an index of viability was in the 97-99% range. Examole 3
  • Example 2 a dog heart was surgically removed as described in Example 1 and perfused in accordance with the procedure outlined in Example 2.
  • This example differs from the prior examples in that it represents the first implementation of normothermic perfusion using an FC-43 fluorocarbon emulsion in addition to hypothermic intracellular electrolyte perfusion.
  • a 1-hour normothermic perfusion was performed immediately prior to and following the 24-hour hypothermic electrolyte perfusion.
  • the perfused canine heart exhibited excellent ventricular contractility at normothermic conditions after 24 hours.
  • the extracellular and intracellular electrolyte solutions used are those found in Tables I and II, respectively.
  • the autopsy results on the heart used in Example 3 were excellent, indicating very little damage or edema.
  • the system may be used to maintain any number of donor organs, and is not restricted to use with human or animal hearts. It is also apparent that additional advantages and modifications of the present invention will readily occur to those skilled in the art. The invention in its broader aspects is therefore not limited to the specific details, representative apparatus, and the illustrative examples shown and described. Accordingly, departures may be made from the detail without departing from the spirit or scope of the disclosed general inventive concept.

Abstract

Ce système permet la conservation extracorporelle d'un organe jusqu'à ce qu'il puisse être transplanté. On utilise une émulsion de perfusion primaire (3) à base de fluorocarbones pour fournir à l'organe (1) les substances nutritives et pour éliminer les déchets produits par l'organe. La solution introduite dans l'organe est oxygénée (8) et reçoit une substance nutritive supplémentaire (6) avant d'entrer dans l'organe. Le système maintient également les niveaux appropriés de température, pression, concentration d'oxygène et pH du fluide nutritif. Le fluide usé (17) est filtré avant d'être recyclé pour apporter de nouveau de l'oxygène et des substances nutritives à l'organe.
PCT/US1988/000103 1987-01-16 1988-01-15 Systeme de perfusion totale pour organes WO1988005261A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US409287A 1987-01-16 1987-01-16
US004,092 1987-01-16

Publications (1)

Publication Number Publication Date
WO1988005261A1 true WO1988005261A1 (fr) 1988-07-28

Family

ID=21709094

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1988/000103 WO1988005261A1 (fr) 1987-01-16 1988-01-15 Systeme de perfusion totale pour organes

Country Status (1)

Country Link
WO (1) WO1988005261A1 (fr)

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0376763A2 (fr) * 1988-10-26 1990-07-04 McKelvey, Karen Dispositif de transport d'organes humains destinés à la transplantation
EP0553401A1 (fr) * 1992-01-18 1993-08-04 Hugo Sachs Elektronik Dispositif de perfusion
EP0594733A1 (fr) * 1991-07-08 1994-05-04 The American National Red Cross Appareil et methode de perfusion sous cryoprotection controlee par ordinateur
US5723282A (en) * 1991-07-08 1998-03-03 The American National Red Cross Method of preparing organs for vitrification
WO1999015011A1 (fr) * 1997-09-23 1999-04-01 Hassanein Waleed H Compositions, procedes et dispositifs permettant de conserver un organe
US6046046A (en) * 1997-09-23 2000-04-04 Hassanein; Waleed H. Compositions, methods and devices for maintaining an organ
WO2000018226A2 (fr) * 1998-09-29 2000-04-06 Organ Recovery Systems, Inc. Dispositif et procede permettant de maintenir et/ou de restaurer la viabilite d'organes
WO2002089571A1 (fr) * 2001-05-04 2002-11-14 Breonics, Inc. Compartiment pour organe destine a un systeme de support metabolique exsanguin
EP1301226A2 (fr) * 2000-07-19 2003-04-16 Neuron Therapeutics, Inc. Kits et compositions pour la realisation d'injections intracraniennes
US6582953B2 (en) 1999-04-14 2003-06-24 Breonics, Inc. Organ chamber for exsanguinous metabolic support system
US6642045B1 (en) * 1997-04-14 2003-11-04 Breonics, Inc. System for exsanguinous metabolic support of an organ or tissue
WO2005099588A2 (fr) * 2004-04-05 2005-10-27 Organ Recovery Systems, Inc. Appareil et procede pour perfuser un organe ou tissu pour isoler des cellules dans cet organe ou ce tissu.
US6977140B1 (en) * 1998-09-29 2005-12-20 Organ Recovery Systems, Inc. Method for maintaining and/or restoring viability of organs
US20080234768A1 (en) * 2007-03-20 2008-09-25 Transmedics, Inc Systems for monitoring and applying electrical currents in an organ perfusion system
US7572622B2 (en) 2002-08-14 2009-08-11 Transmedic, Inc. Heart preservation chamber
US7811808B2 (en) 2003-07-30 2010-10-12 Organ Assist B.V. Portable preservation apparatus for a donor organ
EP2258176A2 (fr) 2000-08-25 2010-12-08 Organ Recovery Systems, Inc. Procédé de conservation et/ou restauration de la viabilité d'organes
JP2012255003A (ja) * 2004-10-07 2012-12-27 Transmedics Inc ｅｘ−ｖｉｖｏでの臓器管理のためのシステム及び方法
US8409846B2 (en) 1997-09-23 2013-04-02 The United States Of America As Represented By The Department Of Veteran Affairs Compositions, methods and devices for maintaining an organ
US8741555B2 (en) 2004-05-14 2014-06-03 Organ Recovery Systems, Inc. Apparatus and method for perfusion and determining the viability of an organ
US8765364B2 (en) 2007-05-18 2014-07-01 Lifeline Scientific, Inc. Ex vivo methods for validating substance testing with human organs and/or tissues
US8771930B2 (en) 2007-05-18 2014-07-08 Lifeline Scientific, Inc. Ex vivo methods for testing toxicity of substances using donated human organs or tissues
WO2014160989A3 (fr) * 2013-03-28 2014-11-20 The Trustees Of Columbia University In The City Of New York La reperfusion par des glycérides oméga-3 favorise la protection d'un organe de donneur pour la greffe
AU2012216796B2 (en) * 2004-10-07 2014-11-27 Transmedics, Inc. Systems and methods for ex-vivo organ care
US9078428B2 (en) 2005-06-28 2015-07-14 Transmedics, Inc. Systems, methods, compositions and solutions for perfusing an organ
US9084801B2 (en) 2005-11-14 2015-07-21 The Trustees Of Columbia University In The City Of New York Use of an omega-3 lipid-based emulsion following ischemic injury to provide protection and recovery in human organs
US9144562B2 (en) 2006-09-19 2015-09-29 The Trustees Of Columbia University In The City Of New York Omega-3 diglyceride emulsions
US9247728B2 (en) 2008-01-31 2016-02-02 Transmedics, Inc. Systems and methods for ex vivo lung care
US9301519B2 (en) 2004-10-07 2016-04-05 Transmedics, Inc. Systems and methods for ex-vivo organ care
CN106659150A (zh) * 2014-03-26 2017-05-10 D·弗里德 用于维护被收获的待移植心脏的设备
US9894894B2 (en) 2004-10-07 2018-02-20 Transmedics, Inc. Systems and methods for ex-vivo organ care and for using lactate as an indication of donor organ status
US10076112B2 (en) 2014-06-02 2018-09-18 Transmedic, Inc. Ex vivo organ care system
US10176887B1 (en) 2005-11-14 2019-01-08 Organ Recovery Systems, Inc. Ex vivo methods for drug discovery, development and testing
US10194655B2 (en) 2015-09-09 2019-02-05 Transmedics, Inc. Aortic cannula for ex vivo organ care system
US20200138015A1 (en) * 2017-04-04 2020-05-07 University Health Network Apparatus and Methods for Irradiating Organ Perfusates
WO2020145814A1 (fr) * 2019-01-10 2020-07-16 Organ Assist B.V. Appareil et procédé de mesure ex-vivo des performances d'un cœur de donneur
US20200253195A1 (en) * 2017-04-04 2020-08-13 University Health Network Apparatus and Methods for Irradiating Organ Perfusates
US11856944B2 (en) 2011-04-14 2024-01-02 Transmedics, Inc. Organ care solution for ex-vivo machine perfusion of donor lungs
US11963526B2 (en) 2021-07-09 2024-04-23 Transmedics, Inc. Apparatus and method for organ perfusion

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3753865A (en) * 1971-03-12 1973-08-21 Univ California Method and apparatus for preserving human organs extracorporeally
US3772153A (en) * 1969-04-02 1973-11-13 Air Liquide Apparatus for the preservation of animal or human organs in living condition
US3911138A (en) * 1973-02-26 1975-10-07 Children S Hospital Inc Of Cin Artificial blood and method for supporting oxygen transport in animals
US4105798A (en) * 1976-07-19 1978-08-08 Sun Ventures, Inc. Perfluoro polycyclic compounds for use as synthetic blood and perfusion media
EP0125847A2 (fr) * 1983-05-11 1984-11-21 Reneau, Inc. Procédé et appareil pour la conservation hyperbarique d'organes vivants
US4713055A (en) * 1983-06-22 1987-12-15 Viggiano Donato A Artificially vascularized graft

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3772153A (en) * 1969-04-02 1973-11-13 Air Liquide Apparatus for the preservation of animal or human organs in living condition
US3753865A (en) * 1971-03-12 1973-08-21 Univ California Method and apparatus for preserving human organs extracorporeally
US3911138A (en) * 1973-02-26 1975-10-07 Children S Hospital Inc Of Cin Artificial blood and method for supporting oxygen transport in animals
US3911138B1 (en) * 1973-02-26 1996-10-29 Childrens Hosp Medical Center Artificial blood and method for supporting oxygen transport in animals
US4105798A (en) * 1976-07-19 1978-08-08 Sun Ventures, Inc. Perfluoro polycyclic compounds for use as synthetic blood and perfusion media
EP0125847A2 (fr) * 1983-05-11 1984-11-21 Reneau, Inc. Procédé et appareil pour la conservation hyperbarique d'organes vivants
US4713055A (en) * 1983-06-22 1987-12-15 Viggiano Donato A Artificially vascularized graft

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Potential Uses of Perfluorochemical Artificial Blood for Experimental Studies in Physiology, Biology, Biochemistry, Chemotherapy, Toxicology, Metabolism, etc.: FC-43 Emulsion", published 1976, September 4, by The Green Cross Corporation (Osaka, Japan), Technical Information Ser. No. 3, see pages 1 to 20 especially pages 1 to 3, 11 to 13, 17 and 18. *

Cited By (97)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0376763A3 (fr) * 1988-10-26 1992-04-01 McKelvey, Karen Dispositif de transport d'organes humains destinés à la transplantation
EP0376763A2 (fr) * 1988-10-26 1990-07-04 McKelvey, Karen Dispositif de transport d'organes humains destinés à la transplantation
US6187529B1 (en) 1991-07-08 2001-02-13 The American National Red Cross Method for preparing organs for transplantation after cryopreservation
EP0594733A1 (fr) * 1991-07-08 1994-05-04 The American National Red Cross Appareil et methode de perfusion sous cryoprotection controlee par ordinateur
EP0594733A4 (fr) * 1991-07-08 1994-11-30 American Nat Red Cross Appareil et methode de perfusion sous cryoprotection controlee par ordinateur.
US5723282A (en) * 1991-07-08 1998-03-03 The American National Red Cross Method of preparing organs for vitrification
US5821045A (en) * 1991-07-08 1998-10-13 The American National Red Cross Methods for removal of cryoprotectant from organs prior to transplantation
US5962214A (en) * 1991-07-08 1999-10-05 The United States Of America As Represented By The American National Red Cross Method of preparing tissues and cells for vitrification
EP0553401A1 (fr) * 1992-01-18 1993-08-04 Hugo Sachs Elektronik Dispositif de perfusion
US6642045B1 (en) * 1997-04-14 2003-11-04 Breonics, Inc. System for exsanguinous metabolic support of an organ or tissue
US6100082A (en) * 1997-09-23 2000-08-08 Hassanein; Waleed H. Perfusion apparatus and method including chemical compositions for maintaining an organ
US6046046A (en) * 1997-09-23 2000-04-04 Hassanein; Waleed H. Compositions, methods and devices for maintaining an organ
US8409846B2 (en) 1997-09-23 2013-04-02 The United States Of America As Represented By The Department Of Veteran Affairs Compositions, methods and devices for maintaining an organ
AU728233B2 (en) * 1997-09-23 2001-01-04 Department Of Veteran Affairs, The Compositions, methods and devices for maintaining an organ
US9756849B2 (en) 1997-09-23 2017-09-12 The Department Of Veteran Affairs Compositions, methods and devices for maintaining an organ
JP2001516768A (ja) * 1997-09-23 2001-10-02 ハッサネイン，ワリード，エイチ． 臓器を維持するための組成物、方法及び装置
US9756850B2 (en) 1997-09-23 2017-09-12 The Department Of Veteran Affairs Compositions, methods and devices for maintaining an organ
US9756851B2 (en) 1997-09-23 2017-09-12 The Department Of Veteran Affairs Compositions, methods and devices for maintaining an organ
WO1999015011A1 (fr) * 1997-09-23 1999-04-01 Hassanein Waleed H Compositions, procedes et dispositifs permettant de conserver un organe
WO2000018226A2 (fr) * 1998-09-29 2000-04-06 Organ Recovery Systems, Inc. Dispositif et procede permettant de maintenir et/ou de restaurer la viabilite d'organes
WO2000018226A3 (fr) * 1998-09-29 2000-05-25 Life Science Holdings Inc Dispositif et procede permettant de maintenir et/ou de restaurer la viabilite d'organes
US6977140B1 (en) * 1998-09-29 2005-12-20 Organ Recovery Systems, Inc. Method for maintaining and/or restoring viability of organs
US8962303B2 (en) 1998-09-29 2015-02-24 Lifeline Scientific, Inc. Apparatus and method for maintaining and/or restoring viability of organs
US6582953B2 (en) 1999-04-14 2003-06-24 Breonics, Inc. Organ chamber for exsanguinous metabolic support system
EP1301226A2 (fr) * 2000-07-19 2003-04-16 Neuron Therapeutics, Inc. Kits et compositions pour la realisation d'injections intracraniennes
EP1301226A4 (fr) * 2000-07-19 2004-07-14 Neuron Therapeutics Inc Kits et compositions pour la realisation d'injections intracraniennes
EP2301336A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Procédé pour transporter et stocker d'organes
EP2301337A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Appareil pour tenir d'organes
EP2258176A2 (fr) 2000-08-25 2010-12-08 Organ Recovery Systems, Inc. Procédé de conservation et/ou restauration de la viabilité d'organes
EP2258175A2 (fr) 2000-08-25 2010-12-08 Organ Recovery Systems, Inc. Appareil de conservation et/ou restauration de la viabilité d'organes
EP2301339A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Procédé pour maintenir et/ou restaurer la viabilité d'organes
EP2301342A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Procédé pour controller l'opération d'un transporteur
EP2301340A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Appareil portatif pour transporter d'organes
EP2301335A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Appareil pour tenir d'organes
EP2301338A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Appareil pour perfuser d'organes
EP2308291A2 (fr) 2000-08-25 2011-04-13 Organ Recovery Systems, Inc. Procédé pour tenir d'organes
EP2308293A2 (fr) 2000-08-25 2011-04-13 Organ Recovery Systems, Inc. Procédé pour maintenir et/ou restaurer la viabilité d'organes
EP2301334A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Procédé pour transporter et stocker d'organes
EP2301341A2 (fr) 2000-08-25 2011-03-30 Organ Recovery Systems, Inc. Appareil pour tenir d'organes
EP2308292A2 (fr) 2000-08-25 2011-04-13 Organ Recovery Systems, Inc. Appareil pour tenir d'organes
EP2308294A2 (fr) 2000-08-25 2011-04-13 Organ Recovery Systems, Inc. Procédé pour maintenir et/ou restaurer la viabilité d'organes
WO2002089571A1 (fr) * 2001-05-04 2002-11-14 Breonics, Inc. Compartiment pour organe destine a un systeme de support metabolique exsanguin
US7572622B2 (en) 2002-08-14 2009-08-11 Transmedic, Inc. Heart preservation chamber
US7811808B2 (en) 2003-07-30 2010-10-12 Organ Assist B.V. Portable preservation apparatus for a donor organ
WO2005099588A2 (fr) * 2004-04-05 2005-10-27 Organ Recovery Systems, Inc. Appareil et procede pour perfuser un organe ou tissu pour isoler des cellules dans cet organe ou ce tissu.
US8389280B2 (en) 2004-04-05 2013-03-05 Organ Recovery Systems Method for perfusing an organ for isolating cells from the organ
US9706769B2 (en) 2004-04-05 2017-07-18 Organ Recovery Systems, Inc Apparatus and method for maintaining and/or restoring viability of organs
US7504201B2 (en) * 2004-04-05 2009-03-17 Organ Recovery Systems Method for perfusing an organ and for isolating cells from the organ
WO2005099588A3 (fr) * 2004-04-05 2006-04-13 Organ Recovery Systems Inc Appareil et procede pour perfuser un organe ou tissu pour isoler des cellules dans cet organe ou ce tissu.
US8741555B2 (en) 2004-05-14 2014-06-03 Organ Recovery Systems, Inc. Apparatus and method for perfusion and determining the viability of an organ
US10314303B2 (en) 2004-10-07 2019-06-11 Transmedics, Inc. Systems and methods for ex-vivo organ care
US11723357B2 (en) 2004-10-07 2023-08-15 Transmedics, Inc. Systems and methods for ex-vivo organ care
US9055740B2 (en) 2004-10-07 2015-06-16 Transmedics, Inc. Systems and methods for ex-vivo organ care
AU2012216796B2 (en) * 2004-10-07 2014-11-27 Transmedics, Inc. Systems and methods for ex-vivo organ care
US10736314B2 (en) 2004-10-07 2020-08-11 Transmedics, Inc. Systems and methods for ex-vivo organ care and for using lactate as an indication of donor organ status
JP2012255003A (ja) * 2004-10-07 2012-12-27 Transmedics Inc ｅｘ−ｖｉｖｏでの臓器管理のためのシステム及び方法
US9215867B2 (en) 2004-10-07 2015-12-22 Transmedics, Inc. Systems and methods for ex-vivo organ care
US9894894B2 (en) 2004-10-07 2018-02-20 Transmedics, Inc. Systems and methods for ex-vivo organ care and for using lactate as an indication of donor organ status
US9301519B2 (en) 2004-10-07 2016-04-05 Transmedics, Inc. Systems and methods for ex-vivo organ care
JP2016053030A (ja) * 2004-10-07 2016-04-14 トランスメディクス， インク．Ｔｒａｎｓｍｅｄｉｃｓ， Ｉｎｃ． ｅｘ−ｖｉｖｏでの臓器管理のためのシステム及び方法
US10321676B2 (en) 2004-10-07 2019-06-18 Transmedics, Inc. System and methods for ex-vivo organ care and for using lactate as an indication of donor organ status
US11570985B2 (en) 2004-10-07 2023-02-07 Transmedics, Inc. Systems and methods for ex-vivo organ care and for using lactate as an indication of donor organ status
US11191263B2 (en) 2004-10-07 2021-12-07 Transmedics, Inc. Systems and methods for ex-vivo organ care
JP2017071622A (ja) * 2004-10-07 2017-04-13 トランスメディクス， インク．Ｔｒａｎｓｍｅｄｉｃｓ， Ｉｎｃ． ｅｘ−ｖｉｖｏでの臓器管理のためのシステム及び方法
US11844345B2 (en) 2005-06-28 2023-12-19 Transmedics, Inc. Systems, methods, compositions and solutions for perfusing an organ
US9078428B2 (en) 2005-06-28 2015-07-14 Transmedics, Inc. Systems, methods, compositions and solutions for perfusing an organ
US10039276B2 (en) 2005-06-28 2018-08-07 Transmedics, Inc. Systems, methods, compositions and solutions for perfusing an organ
US9084801B2 (en) 2005-11-14 2015-07-21 The Trustees Of Columbia University In The City Of New York Use of an omega-3 lipid-based emulsion following ischemic injury to provide protection and recovery in human organs
US10176887B1 (en) 2005-11-14 2019-01-08 Organ Recovery Systems, Inc. Ex vivo methods for drug discovery, development and testing
US9144562B2 (en) 2006-09-19 2015-09-29 The Trustees Of Columbia University In The City Of New York Omega-3 diglyceride emulsions
US9457179B2 (en) * 2007-03-20 2016-10-04 Transmedics, Inc. Systems for monitoring and applying electrical currents in an organ perfusion system
US10327443B2 (en) 2007-03-20 2019-06-25 Transmedics, Inc. Systems for monitoring and applying electrical currents in an organ perfusion system
US20080234768A1 (en) * 2007-03-20 2008-09-25 Transmedics, Inc Systems for monitoring and applying electrical currents in an organ perfusion system
US11917991B2 (en) 2007-03-20 2024-03-05 Transmedics, Inc. Systems for monitoring and applying electrical currents in an organ perfusion system
US8771930B2 (en) 2007-05-18 2014-07-08 Lifeline Scientific, Inc. Ex vivo methods for testing toxicity of substances using donated human organs or tissues
US8765364B2 (en) 2007-05-18 2014-07-01 Lifeline Scientific, Inc. Ex vivo methods for validating substance testing with human organs and/or tissues
US10750738B2 (en) 2008-01-31 2020-08-25 Transmedics, Inc. Systems and methods for ex vivo lung care
US9814230B2 (en) 2008-01-31 2017-11-14 Transmedics, Inc. Systems and methods for ex vivo lung care
US9247728B2 (en) 2008-01-31 2016-02-02 Transmedics, Inc. Systems and methods for ex vivo lung care
US9462802B2 (en) 2008-01-31 2016-10-11 Transmedics, Inc. Systems and methods for ex vivo lung care
US9516875B2 (en) 2008-01-31 2016-12-13 Transmedics, Inc. Systems and methods for ex vivo lung care
US11856944B2 (en) 2011-04-14 2024-01-02 Transmedics, Inc. Organ care solution for ex-vivo machine perfusion of donor lungs
US11076593B2 (en) 2013-03-28 2021-08-03 The Trustees Of Columbia University In The City Of New York Reperfusion with omega-3 glycerides promotes donor organ protection for transplantation
WO2014160989A3 (fr) * 2013-03-28 2014-11-20 The Trustees Of Columbia University In The City Of New York La reperfusion par des glycérides oméga-3 favorise la protection d'un organe de donneur pour la greffe
US10070643B2 (en) 2013-03-28 2018-09-11 The Trustees Of Columbia University In The City Of New York Reperfusion with omega-3 glycerides promotes donor organ protection for transplantation
CN106659150A (zh) * 2014-03-26 2017-05-10 D·弗里德 用于维护被收获的待移植心脏的设备
US11944088B2 (en) 2014-06-02 2024-04-02 Transmedics, Inc. Ex vivo organ care system
US10076112B2 (en) 2014-06-02 2018-09-18 Transmedic, Inc. Ex vivo organ care system
US11903381B2 (en) 2014-06-02 2024-02-20 Transmedics, Inc. Ex vivo organ care system
US11154050B2 (en) 2014-06-02 2021-10-26 Transmedics, Inc. Ex vivo organ care system
US11122795B2 (en) 2015-09-09 2021-09-21 Transmedics, Inc. Aortic cannula for ex vivo organ care system
US10194655B2 (en) 2015-09-09 2019-02-05 Transmedics, Inc. Aortic cannula for ex vivo organ care system
US20200138015A1 (en) * 2017-04-04 2020-05-07 University Health Network Apparatus and Methods for Irradiating Organ Perfusates
US20200253195A1 (en) * 2017-04-04 2020-08-13 University Health Network Apparatus and Methods for Irradiating Organ Perfusates
EP3606564A4 (fr) * 2017-04-04 2021-04-14 University Health Network Appareil et procédés destinés à exposer des perfusats d'organe à un rayonnement
WO2020145814A1 (fr) * 2019-01-10 2020-07-16 Organ Assist B.V. Appareil et procédé de mesure ex-vivo des performances d'un cœur de donneur
US11963526B2 (en) 2021-07-09 2024-04-23 Transmedics, Inc. Apparatus and method for organ perfusion

Similar Documents

Publication Publication Date Title
WO1988005261A1 (fr) Systeme de perfusion totale pour organes
JP6347565B2 (ja) 臓器を維持するための組成物、方法及び装置
DE69819759T2 (de) Zusammensetzungen, verfahren und vorrichtungen zur aufrechterhaltung eines organs
US5338662A (en) Organ perfusion device
WO2020192513A1 (fr) Dispositif de conservation de perfusion mécanique pour des organes d'un corps vivant
US7575856B2 (en) Compositions and methods for the evaluation and resuscitation of cadaveric hearts for transplant
ES2795453T3 (es) Métodos y aparatos para el soporte de órganos
ES2916212T3 (es) Aparato para conservación de corazones recolectados para trasplante
WO2006118990A2 (fr) Procede et dispositif destines a la perfusion d'organe
JPH0499701A (ja) 移植に使用するヒトの臓器の輸送用装置
JP2024042048A (ja) 器官維持および輸送のためのシステムならびに方法
Boettcher et al. History of extracorporeal circulation: the conceptional and developmental period
US20180271087A1 (en) Device for vascularized composite allotransplant preservation and use thereof
WO2022055464A1 (fr) Bain d'organe sanguin entier vivant
CN114514922A (zh) 一种离体心脏常温机械灌注装置
Smith Studies with a pulsatile pump-oxygenator system for preservation of canine kidneys
JP2009524693A (ja) 非再循環式臓器灌流装置

Legal Events

Date Code Title Description
AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE