JP2020114447A - System and method for providing zone for selective temperature therapy - Google Patents

Abstract

To provide a system and a method for establishing at least two zones for a selective temperature therapy of a body.SOLUTION: An extracorporeal circuit 700 including three ports 711, 715, 721 usable for establishing at least two zones for a selective temperature therapy of a body, also includes a branch section 718 capable of setting each blood temperature to be injected into two different parts of the body at different temperature levels, in order to provide two zones for the selective temperature therapy.SELECTED DRAWING: Figure 7A

Description

Hypothermia, a controlled decrease in temperature of a part of the body, can be used to provide several therapeutic benefits. Thus, hypothermia may be deliberately induced as therapeutic hypothermia in certain procedures. For example, in the medical community, hypothermia is considered a commonly accepted neuroprotection during cardiovascular surgery. Hypothermia may also be induced as neuroprotection during neurosurgery. Therapeutic hypothermia can be beneficially used to prevent or reduce the effects of tissue damage from ischemic injury and other injuries. For example, the tissue damage that occurs after ischemic injury begins with the onset of ischemia and continues throughout the reperfusion phase after blood flow is restored. The observation that the reperfusion phase can last for hours to days, and that therapeutic hypothermia can be beneficially used to block many of the injuries at that phase, is both a preclinical and clinical trial. Supported by.

The present disclosure provides exemplary systems, devices, apparatus, and methods that use a three-port extracorporeal circuit to provide at least two zones of selective body temperature therapy. An exemplary three-port extracorporeal circuit provides branching that sets the temperature of blood injected into two different parts of the body to different temperature levels, thereby providing at least two zones of selective temperature therapy. Including section.

An exemplary extracorporeal circuit includes an injector member including a distal tip disposed in a vascular position, a first port for drawing blood from the body, and a second port for returning blood to the body. A first pump disposed between the first port and the second port for pumping blood from the first port to the second port; a first pump and a second port; A branch section positioned between and a third port coupled to the branch section. The third port is positioned external to the injector member and the second pump is positioned between the bifurcation section and the third port.

The exemplary system also includes a first heat exchanger disposed between the first port and the second port and a second heat exchanger disposed between the second pump and the injector member. And a heat exchanger of. The first heat exchanger can be configured to set the temperature of the blood injected into the second port to the first temperature level. The second heat exchanger can be configured to set the temperature of the blood injected into the injector member to a second temperature level that is different than the first temperature level. The first heat exchanger can be arranged between the branch section and the first port or between the branch section and the second port.

An exemplary system for providing at least two zones of selective temperature therapy can include an occlusion component or an additional minimum conductance component disposed proximate the distal tip of the injector member. ..

An exemplary system for providing at least two zones of selective temperature therapy includes a proximal distal tip used to calculate a conductance value of a portion of the vasculature outside the injector member. A controlled flow splitting system at.

An exemplary controlled flow splitting system includes a first pressure sensor for measuring a first pressure proximate a distal tip of at least one injector member and a distal pressure sensor for measuring a second pressure. A second pressure sensor disposed proximally from the tip. The second pump serves as an injection flow source for producing an injection flow in the injector member in a predetermined flow pattern.

Described are exemplary systems, devices, and apparatus for providing assistance, including a whole body extraperfusion circuit (SPEC), a local extraperfusion circuit (LPEC) for perfusing a local target area of the body, and a console. To be done. The SPEC includes a SPEC input flow port, a SPEC output flow port, and a SPEC pump. The SPEC input and SPEC output flow ports are in contact with blood flowing within the vasculature at a peripheral portion of the body. The LPEC includes a LPEC input flow port, a LPEC output flow port, a LPEC pump, and a LPEC heat exchanger. The LPEC input flow port and the LPEC output flow port are in contact with blood flowing through the vasculature toward a target area of the body. The LPEC heat exchanger controls the temperature of blood returning to a local target area of the body due to local perfusion. A controlled flow splitting system is located proximate the distal tip of the LPEC injector member. The controlled flow splitting system includes a first pressure sensor for measuring a first pressure proximate the distal tip of the LPEC injector member and a second pressure sensor for measuring a second pressure. .. The second pressure sensor is disposed proximally from the distal tip of the LPEC injector member. The second pump serves as an injection flow source for producing an injection flow in the injector member in a predetermined flow pattern. One or more SPEC temperature sensors are coupled to the body to indicate an average core body temperature and/or an average system temperature of the body perfused by SPEC. One or more LPEC temperature sensors are coupled to the local target area of the body to indicate the temperature within the target area. The console receives data indicative of measurements of the first pressure and the second pressure over a time interval T with blood flow infused at the distal tip in a predetermined flow pattern, and the first The data indicating the pressure and the second pressure measurement and the predetermined flow pattern are used to determine the conductance as at least one of the proximal or distal outer conductance at the distal tip of the LPEC injector member. And at least one processing unit programmed to perform.

Exemplary systems, devices, and apparatus establish two different temperature zones of at least a portion of the body to perform at least a portion of a treatment procedure for a patient suffering from local or systemic ischemic injury or circulatory injury, and The method for controlling can be configured to implement. An exemplary method includes coupling a systemic extraperfusion circuit (SPEC) to the body using a peripherally located loop, and connecting the local extraperfusion circuit (LPEC) to a local target area of the body. Binding to blood flowing through the structure. The SPEC includes SPEC input and SPEC output flow ports for contacting blood flowing within the vasculature, a SPEC pump, and a SPEC heat exchanger. The LPEC includes an LPEC injector member with a distal tip that contacts blood flowing within the vasculature, an LPEC pump, and an LPEC heat exchanger. The LPEC injector member is arranged to perfuse a localized target area of the body. At least one of the additional minimum conductance components or controlled flow splitting system is disposed proximate the distal tip of the LPEC injector member. The method comprises locating at least one SPEC sensor for measuring an average core body temperature and/or an average system temperature of a body perfused by SPEC, and measuring the temperature of a local target area perfused by LPEC. Positioning at least one LPEC sensor for measuring, performing an operating step of at least a minimum operating sequence, recording the measurements of the at least one LPEC sensor and at least one SPEC sensor, and Performing a control procedure for independently controlling the blood flow rate and the heat exchanger temperature of each of the SPEC and LPEC. The control procedure causes the SPEC to control the temperature of the blood infused by the SPEC to adjust the temperature readings reported by the SPEC temperature sensor to stay within the target core body temperature range, one or more. Causes the LPEC to control the temperature of the blood infused into the target area so that the LPEC temperature sensor of 1 reports a temperature measurement according to a particular pattern of target area temperature values.

Described are exemplary systems, devices, and apparatus for providing selective temperature therapy. The exemplary system defines a first lumen distal end, a first lumen proximal end, and a first lumen having a length from the proximal end to the distal end. A first elongate element having a first wall formed therein, the first lumen being a delivery lumen for delivering temperature-treated blood to a target site in the body; An outlet port is located in the cavity, the outlet port for delivering temperature treated blood to a target site, and at least one of the additional minimum conductance components or the controlled flow splitting system being in proximity to the outlet port. A first elongate element positioned in the first lumen at a position and a second elongate element having a second wall can be included. The second lumen is defined as the space between the first wall and the second wall, the second lumen is coaxial with the first lumen, and the second lumen is the second lumen. A luminal proximal end and a second luminal distal end. The second lumen is a supply lumen for receiving normothermic blood from the body, and the second lumen is insulated along most of the length of the first lumen when receiving normothermic blood. A second lumen distal end is positioned relative to the first lumen distal end such that the second lumen distal end is in proximity to the first lumen distal end to function as a layer. The distal lumen end is located. The second elongate element is insertable into a body artery at a peripheral location of the body and is adapted to extend to a distant location of the body. An exemplary system is an inlet located in the second elongate element proximate at least one of the additional minimal conductance components or the controlled flow splitting system and having an inlet for receiving normothermic blood. Including. The exemplary system is a control unit in fluid communication with the proximal ends of the first and second lumens and a supply blood inlet in fluid communication with the second lumen. And a temperature controller in fluid communication with the supply blood inlet, the control unit having a supply blood inlet for receiving normothermic blood from the body. A temperature regulator configured to provide conditioned blood, a delivery blood outlet in fluid communication with the temperature regulator and in fluid communication with the first lumen, And a delivery blood outlet for providing to the first lumen.

Described are exemplary systems, devices, and apparatus for providing selective temperature therapy. An exemplary device is a first elongate element having a first wall, wherein the space within the first wall defines a delivery lumen, and the second elongate element and the second wall. A second elongate element having a feed lumen and a delivery lumen, the feed lumen being defined by a space between the first wall and the second wall. And a control unit in fluid communication with. The control unit includes a supply blood inlet in fluid communication with the supply lumen, a supply blood inlet for receiving normothermic blood from the body, and a delivery blood outlet in fluid communication with the delivery lumen. A delivery blood outlet for providing temperature-treated blood to the delivery lumen. The supply lumen delivers normothermic blood to a control unit located outside the body. The delivery lumen receives the temperature-treated blood from the control unit and supplies the temperature-treated blood to a target site in the body, the supply lumen being coaxial with the delivery lumen, and the supply lumen being the temperature Positioned around a majority of the delivery lumen such that the supply lumen acts as an insulating layer along the majority of the delivery lumen when receiving treated blood; The control unit and the delivery lumen form a closed system. The second elongate element is insertable into a body artery at a peripheral location of the body and is adapted to extend to a distant location of the body. At least one of the additional minimal conductance component or the controlled flow splitting system is located at a location proximal of the distal end of the delivery lumen and distal of the distal end of the delivery lumen. Located in the lumen.

Any combination of the above concepts with additional concepts discussed in more detail below (provided such concepts are not inconsistent with each other) is not subject to the inventive subject matter disclosed herein. It should be understood that it is considered part. In particular, any combination of claimed subject matter appearing at the end of this disclosure is considered to be part of the inventive subject matter disclosed herein. Also, terms used explicitly herein that may appear in any disclosure incorporated by reference are to be given the meaning most consistent with the particular concept disclosed herein. Should be understood.

Those skilled in the art will appreciate that the drawings are primarily for purposes of illustration and are not intended to limit the scope of the inventive subject matter described herein. The drawings are not necessarily to scale and, in some instances, various aspects of the inventive subject matter disclosed herein may be exaggerated or expanded within the drawings to facilitate understanding of the different features. It may be shown enlarged. In the drawings, like reference numbers generally indicate similar features (eg, functionally similar and/or structurally similar elements).

1 is a schematic diagram of an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 6 is an exemplary plot of fluid conductance in a vascular space that straddles a boundary. FIG. 6 is an exemplary plot of fluid conductance in a vascular space that straddles a boundary. FIG. 4 is a diagram of an exemplary extracorporeal circuit according to the principles of the present disclosure. 3 is a schematic diagram of another catheter system in accordance with the principles of the present disclosure. 3 is a schematic diagram of another catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates another example catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates another example catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates another example catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates another example catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates another example catheter system in accordance with the principles of the present disclosure. (I)(ii) is a diagram illustrating an example of another catheter system according to the principles of the present disclosure. (I)(ii) show examples of biasing valves in the bore of an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates an example of a biasing valve in a hole of an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 6 illustrates an example of a biasing valve in a hole of an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 8 is a diagram of an exemplary injector member coupled to a pressure sensor in an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 8 is a view of another exemplary injector member coupled to a pressure sensor in an exemplary catheter system in accordance with the principles of the present disclosure. FIG. 6 is an illustration of an exemplary catheter coupled to a pressure sensor according to the principles of the present disclosure. FIG. 8 is a diagram of another exemplary catheter coupled to a pressure sensor according to the principles of the present disclosure. 1 is a diagram of an exemplary extracorporeal circuit system in accordance with the principles of the present disclosure. FIG. 7 is a diagram of another extracorporeal circuit system in accordance with the principles of the present disclosure. FIG. 7 is a diagram of another extracorporeal circuit system in accordance with the principles of the present disclosure. FIG. 3 is a diagram of an exemplary extracorporeal circuit system coupled to a console according to the principles of the present disclosure. FIG. 8 is a diagram of another exemplary extracorporeal circuit system coupled to a console in accordance with the principles of the present disclosure. FIG. 6 is a block diagram illustrating an exemplary computing device in accordance with the principles of the present disclosure. FIG. 6 is a flow diagram illustrating an exemplary method in accordance with the principles of the present disclosure. FIG. 6 is a flow diagram illustrating an exemplary method in accordance with the principles of the present disclosure. FIG. 6 is a block diagram of an exemplary computing device in accordance with the principles of the present disclosure.

The following is a more detailed description of various concepts, and embodiments thereof, of systems, devices, apparatus, and methods that enable control of at least two zones of selective temperature therapy. The various concepts introduced above and discussed in further detail below may be implemented in any of a number of ways, as the disclosed concepts are not limited to any particular implementation. May be done. Examples of specific implementations and applications are provided primarily for purposes of illustration.

As used herein, the term "includes" means including but not limited to, and the term "including" includes but is not limited to. means. The term "based on" means based at least in part.

Indicating the relative position, alignment, and/or orientation of the various elements/components with respect to the substrate and with respect to each other with respect to the surfaces described herein in connection with various examples of the principles herein. For this purpose, any reference to the "top" and "bottom" planes is used, and these terms do not necessarily refer to any particular reference frame (eg gravity reference frame). is not. Thus, reference to "below" a surface or layer does not necessarily require that the indicated surface or layer be facing the ground. Similarly, terms such as "over," "under," "above," "beneath," etc. refer to any particular reference, such as a frame of gravity reference. Is not necessarily used to refer to the reference frame of the, but is used primarily to indicate the relative position, alignment, and/or orientation of the various elements/components with respect to the surface and with respect to each other.

The terms "disposed on" and "disposed over" include the meaning of "embedded," including "partially embedded." .. Further, reference to feature A being “disposed on”, “disposed between”, or “disposed over” feature B is: It includes the example that feature A is in contact with feature B, and that other layers and/or other components are located between feature A and feature B.

The term "proximal" as used herein includes a user-operated portion of a catheter, injector member, or other device, such as, but not limited to, a grip or other handle. Points to the direction. As used herein, the term "distal" refers to the direction away from the grip or other handle of a catheter, injector member, or other device. For example, the tip of the injector member is disposed on the distal portion of the injector member.

Described are exemplary systems, devices, apparatus, and methods for controlling at least two zones of selective temperature therapy that allow for controlled temperature reduction of a body part. Exemplary systems, devices, apparatus, and methods are for intentionally inducing therapeutic hypothermia in certain surgical or other medical procedures, such as, but not limited to, cardiovascular surgery or neurosurgery. Can be used for For example, the systems, devices, apparatus, and methods described herein can be used to prevent or reduce tissue damage that can occur following ischemic injury, which tissue damage is usually a manifestation of ischemia. , And continues throughout the reperfusion phase after blood flow is restored. The observation that the reperfusion phase can last for hours to days is supported by both preclinical and clinical studies. Therapeutic hypothermia that can be achieved using the exemplary systems, devices, apparatus and methods described herein blocks many of the injuries or other types of tissue damage at that stage. It can be used beneficially.

Described are exemplary systems, devices, apparatus, and methods for providing at least two zones of selective temperature therapy of the body using a 3-port extracorporeal circuit. An exemplary three-port extracorporeal circuit according to the principles herein sets the temperature of blood injected into two different parts of the body to different temperature levels, thereby providing at least two zones of selective temperature therapy. It includes a branch section that realizes that.

An exemplary extracorporeal circuit includes an injector member including a distal tip disposed in a vascular position, a first port for drawing blood from the body, and a second port for returning blood to the body. A first pump disposed between the first port and the second port for pumping blood from the first port to the second port; a first pump and a second port; A branch section positioned between and a third port coupled to the branch section. The third port is positioned external to the injector member and the second pump is positioned between the bifurcation section and the third port.

Further, during certain procedures using catheters, blood flow in veins or arteries may be occluded. Whenever blood flow is at least partially blocked, regions of no flow or low flow may occur in a portion of the vasculature, including dead zones. For example, a vascular catheter or other similar device may include an occlusive device to control or block flow in an artery or vein. Under certain circumstances, obstructing blood flow in an artery or vein can result in zones of significantly reduced blood flow, or areas of no flow, where the blood is substantially stagnant. These zones are referred to herein as "dead zones" or "flowless zones". Prolonged periods of no or low flow (including dead zones) can lead to tissue deprivation and risk. In some cases, the long-term creation of dead zones in the bloodstream may increase the risk of thrombus or clots associated with increasing the risk of embolism in the patient. Problems arise with how to minimize these risks resulting from blocking.

In some systems, by adding a bypass or perfusion lumen, such as those described in US Pat. Nos. 5,046,503 and 5,176,638, the blood flow supplied by the arteries to the tissue is increased. Address the risk of disconnection.

In this disclosure, various exemplary systems for controlling blood flow in a portion of an artery or vein to control the occurrence of regions of low or no flow in a portion of the vasculature and their duration. , Methods and apparatus are also described. As a non-limiting example, the systems, devices, apparatus, and methods can be used to control the occurrence and duration of dead zone regions in a portion of the vasculature.

In some examples, systems, methods, and apparatus are described for controlling (including reducing) flow stagnation during use of a vascular catheter or other similar device. Exemplary systems, devices, and methods for controlling or reducing the occurrence of no-flow or low-flow zones within a vasculature based on data indicative of conductance of regions of the vasculature are described. .. Control of flow stagnation can be achieved using at least one additional minimum conductance component or using a controlled flow splitting system. The exemplary added minimum conductance component can be used to add a desired known value of conductance to a region of the vasculature. If the conductance outside the injector member is known, be sure that there is an amount of fluid flow to flush the area where normally no or low flow zones (including dead zones) are formed. , The level of fluid injection at the injector member can be controlled. The exemplary controlled flow splitting system can use the sensor measurements to calculate conductance in the region of the vasculature, thereby providing a known value of conductance. That is, any of these system methods can be used to provide a known value of the conductance outside the catheter member. These known values of conductance are used to ensure that no or no flow zones occur in the vasculature, or the duration of the occurrence of no or low flow zones is due to tissue damage or other Fluid flow can be controlled to ensure that it does not lead to damage.

By reducing the occurrence of flow stagnation, the likelihood of forming dead zones or no flow zones in a portion of the vasculature is reduced or eliminated.

According to some exemplary implementations, flow stagnation control can be achieved by using a controlled flow splitting system. The controlled flow splitting system includes components for measuring both proximal and distal outer conductance. A measure for preventing flow dead zones in the region proximal to the injector member by altering the flow injected at the injector member. Exemplary devices, systems, and methods may operate passively to measure fluid flow, or to actively measure fluid flow by introducing or withdrawing a volume of fluid. May be used.

In the present disclosure, a device that can be actively operated to prevent or reduce (including flushing) the occurrence of dead zones that may form in a portion of the vasculature proximate the catheter during operation, Systems and methods are also described.

The term "additional minimum conductance component" is used herein to refer to a component that controls flow reduction in a vasculature segment while preventing flow below a certain minimum value based on the added minimum conductance level. Point to. As used herein, conductance is the reciprocal of resistance. In various examples, controlling the flow to a fixed value of flow rate (referred to herein as a "fixed constant") or over a time cycle t that is less than the length of time T of the procedure, ie, at t<<T, The minimum conductance level can be used to control the flow as an average value of flow rate (referred to herein as the "fixed average"). For example, the time cycle t can be approximately a heartbeat or a few minutes, the period T can be the time of a surgery or other procedure, and lasts for an hour or more.

According to some exemplary embodiments, flow stagnation control is achieved by using additional minimum conductance components and systems configured to allow improved flow control in extracorporeal blood return. be able to. The present disclosure also provides various exemplary additional minimum conductance components that limit or prevent the formation of dead zones in areas of arteries or veins proximate to the additional minimum conductance components, including certain dead zone flushing devices or subsystems. Also provide.

As used herein, an "injector member" is a device or component that contains a lumen. In the example, the lumen is used as a part of an independent catheter system or as a component of an exemplary extracorporeal circuit system used to inject blood into the vasculature at specific locations in the body. It can be used to inject fluid into the vasculature.

As used herein, the term "infusion point of the vasculature" refers to the most distal location of the vasculature away from the catheter entry point or vessel perforation location, where blood is injected into the body. To be done.

The term "peripherally located loop" as used herein refers to blood output (body to circuit) and blood input (circuit to body) catheter (or other input flow port and/or output flow). Port member), which is from a fluoroscopy or any other equivalent system that would normally be used to advance the device past the arterial or venous tributaries. Can be placed in contact with a portion of the body's vasculature without the detailed guidance of This is a subset of all possible configurations, some through the peripheral circulation and some through the central circulation.

The term "peripheral" is used herein in a manner different from that used when referring to the peripheral circulatory system. For example, a catheter (or other input flow port and/or output flow port member) may be placed in contact with the vena cava or under the descending aorta or iliac artery without fluoroscopy. .. These may be considered part of the central system rather than the peripheral circulation system.

The term "systemic perfusion system" as used herein refers to an injector member directly coupled to a main vein that supplies the heart, such as the vena cava (inferior vena cava or superior vena cava) or iliac vein. Refers to a system that is coupled to blood in the heart via.

As used herein, the term "local perfusion system" refers to the blood that is passed to the organ system before a major proportion of the infused blood (greater than about 50%) returns to the heart through the general circulation. Refers to a system having an injector member arranged to be delivered.

The term "proximal external conductance" as used herein refers to the conductance within the space external to the device along a region proximal to the infusion member tip, i.e., between the device and the vessel wall. means.

The term “distal external conductance” as used herein means the total conductance entering the distal vasculature from the injection site at the tip of the injection member. For injection members on the arterial side of the vasculature, the distal outer conductance is the conductance from the tip to the venous side of the circulation.

The term "controlled flow splitting system" as used herein is a system for measuring or calculating the value of either or both of the proximal and distal external conductances, which system then These measurements are used to prevent flow dead zones in the region proximal to the injector member by varying the flow rate injected at the injector member. As used herein, such a system consists of at least two pressure sensors and a positive displacement or flow control pump on the extracorporeal circuit side of the injector member that directly controls the flow rate through the injector member. .. In any example herein, the controlled flow splitting system can include a distributed array of pressure sensors.

The term "flow pattern" as used herein refers to a functional form of flow over a set period of time. For example, the fluid flow can be set at the fluid flow source such that the fluid flow follows the values set by the flow pattern. In various examples, the flow pattern is in a sine function form, a sawtooth function form, a step function form, or another periodic function form in the art (including more complex function forms), etc. It can be a specific functional form that is not limited to. In another example, if the flow pattern has an irregular functional form, the value of the flow rate may be measured at regular time intervals over a particular period of time to provide an irregular functional form approximation. ..

In a non-limiting example herein, the additional minimum conductance component may be configured to set a known specific proximal conductance around the distal region of the infusion member. Its proximal conductance can prevent the formation of any non-flow zone or flow dead zone. As another example, in a controlled flow splitting system according to the principles herein, the conductance at the proximal outer portion of the infusion member is measured (rather than being generated) and that measurement is used to ( Flow rate and flushing of associated zones (including any no-flow zones or flow dead zones) are controlled.

In the examples herein, "biasing valve" refers to the component in the wall of the catheter section between the inner lumen and the outer side of the shaft exposed to the vasculature. In an example, the "biasing valve" may be configured such that if the pressure inside the lumen is greater than the pressure outside the shaft, then there is a conductance value G _forward established across the valve. In another example, the "biasing valve" may be configured such that if the pressure inside the lumen is less than the pressure outside the shaft, there is a conductance value G _backward established across the valve. In the example, appropriate pressure differential between the luminal and Kanmyaku structure _as the _{G forward >>} G _backward, or _{G backward} is very small or substantially zero, can be represented.

FIG. 1A shows a schematic diagram of an exemplary catheter system 100 including a device shaft 101 disposed in a portion of a vasculature. FIG. 1A also shows a plane 102 that is attached to the shaft 101 and passes through the occlusion component 103 that is part of the device. Shaft holding device 101 may include a lumen therethrough. In the exemplary catheter system 100, the occlusion component 103 may include a balloon that is inflated using saline or other solution. Another exemplary occlusion component 103 may include a membrane that is expanded using a force applied by a spring or other mechanical actuation to push against the arterial wall. In an example, the occlusion component 103 may be configured to expand from the shaft device 101 of the catheter system 100 and hit the wall of an artery or vein to seal it and significantly reduce or prevent flow. As shown in FIG. 1A, the exemplary plane 102 is perpendicular to the vessel cross section. The exemplary occlusion component 103 is used in accordance with the principles herein to alter fluid flow across a plane 102. The fluid flow is related to the flow outside the base holding shaft. The degree of flow is driven by the pressure difference between the area (Pb) in front of the occlusion component 103 and the area (Pa) after it.

1B and 1C show exemplary graphs of fluid conductance (G ₀ ) versus time in the vessel space across a plane 102 through the occlusion component 103. FIG. 1B shows the fluid conductance (G ₀ ) versus time when fully occluded using the occlusion component 103. In the example of FIG. 1B, the fluid conductance is reduced for a period Δt when the occluding component is actuated to completely occlude the vessel space. The plot of FIG. 1B shows that the fluid conductance is zero when the occlusion component 103 is actuated to fully occlude. This definition is independent of pressure slope/difference (F=G(Pa-Pb)). The plot of FIG. 1C shows the state of fluid conductance (G ₀ ) versus time during a controlled partial occlusion, with the occlusion component according to the principles herein being activated during a period Δt. As shown in FIG. 1C, the conductance does not go to zero, but to a minimum conductance level with a degree greater than zero.

The catheter can be deployed at various target locations within the vasculature. However, it is very difficult to accurately control the diameter of the vascular structure at the target position. In the absence of the occlusion element or in the unoccluded deployment of the occlusion element, the leakage flow may be high, in which case the leakage flow may optimally control the forward (distal region) fluid flow. May be disturbed. This is limited by the fact that large arteries have large flow and small arteries have small flow. On the other hand, complete occlusion can cause the formation of dead zones. In accordance with the principles herein, a small controlled leak flow structure may be used with the occlusion component, which flushes the dead zone but provides beneficial control of distal flow through use of the device. The leak is limited so that it is not distorted by the leak. For flow rates similar to those of the carotid or femoral arteries, an anterior flow rate of 200-500 ml/min is very useful, but for flushing the dead zone, a flushing flow rate of 20-50 ml/min or less. May be sufficient.

As described herein, the minimum conductance level can be a fixed constant or a fixed average value. For a fixed constant, the fluid conductance G ₀ is constant over time. For a fixed average, the minimum conductance may change over time on a time scale t that is short compared to the overall device activation time. In the example, the biasing valve can be configured such that a controlled partial occlusion is achieved such that the conductance varies over the heartbeat. In this example, "fixed average" refers to the fluid conductance that changes in value during the time cycle of a heart beat, but has a non-zero mean value over that heart beat. This leads to a non-zero mean fluid conductance over a longer period.

In the example, the added minimum conductance is implemented in fixed constant form. An additional minimum conductance component located at the distal tip of the extracorporeal injection member maintains a minimum conductance that provides fluid flow to flush the dead zone normally created by any complete occlusion. Is configured as follows. The magnitude of the minimum conductance flow resistance term is set so that the flushing flow is less than or equal to about 50%, or preferably less than or equal to about 10% of the flow that the device being used conducts through the injector member. It

In the example, the added minimum conductance is realized in a passive fashion. The exemplary occlusion element is configured to include an alternative fluid bypass passage to allow bypass flow to flush the dead zone normally created by an occlusion. The magnitude of the flow resistance term of the bypass is set so that the bypass flow is less than or equal to about 50%, or preferably less than or equal to about 10% of the flow that the device being used conducts through the injector member. ..

In some examples, the occlusion component can include a soft balloon used for occlusion. In an example, the soft balloon may be partially inflated to provide some leakage conductance. This may be useful because the vasculature is uneven and the amount of leakage conductance due to partial inflation is not observable and/or controllable to the user.

FIG. 2A shows a schematic diagram of an exemplary extracorporeal circuit 200 coupled to an individual. The exemplary extracorporeal circuit 200 includes a pump system 206, a heat exchanger 208, and an injector member 210. An exemplary extracorporeal circuit can include two connections to the patient's vasculature. Such exemplary extracorporeal circuits can be implemented to pump blood from the vasculature using one connection and return blood to the vasculature using the other connection. The exemplary extracorporeal circuit can be used when the heart is inoperable or does not supply sufficient blood flow, or is used to modify blood and return it to systemic flow or local areas. May be. Other modifications may include oxygenation, dialysis, heat, removal of bacterial contaminants, removal of carcinogenic cells, and the like. FIG. 2A shows an injector member 210 coupled to the vasculature of an individual's body at a vascular infusion point 212 to return blood 214 to the body based on a regulated flow rate using a pump system 206. .. The most distal location within the vasculature where blood is injected into the body is referred to herein as the "vasculature injection point."

In one example, the injector member 210 can include an occlusion component to separate blood flow on one side from fluid injected by an extracorporeal circuit through the device shaft on the other side. This may create a dead or restricted flow zone, or dead zone, in a portion of the vasculature. Dead zones can be avoided if the occlusion system is placed in the correct position relative to the closest vasculature tributary, but it is not possible to guarantee such exact placement in a real patient. It is possible. As a result, dead zones typically form in tributaries that include infusion points where blood does not flow. This can potentially result in a thrombus or clot if the occlusion is left in place for an extended period of time. The extracorporeal blood supply circuit can be used for extended periods of time, such as, but not limited to, hours to days, but not long enough to increase the risk of clots or clots forming. possible.

2B illustrates an exemplary infuser member 210 that is a component of the exemplary extracorporeal circuit system of FIG. 2A that returns blood to a particular location at a vessel infusion point 212 in the body. Infusion fluid 216 through the shaft lumen can join the bloodstream in this tributary. Infused blood can dominate within the distal vasculature, as long as the alternative blood flow is blocked.

FIG. 2C illustrates an exemplary injector member 210 that is a component of the exemplary extracorporeal circuit system of FIG. 2A that returns blood (infusion fluid 216) to a specific location on the body. Infuser member 210 is coupled to occlusion component 203, which is shown to completely occlude a portion of the vasculature. As shown in FIG. 2C, when the injector member 210 injects blood through the occlusion device 203 at a vascular infusion point, a dead zone 205 may be formed adjacent the occlusion component 203.

3A-3B illustrate an exemplary additive minimum conductance system according to the principles herein. The additional minimum conductance system of FIG. 3A has a lumen having a discontinuous length l disposed along a device shaft, below a component 321, such as but not limited to a soft balloon 321. 320, thereby providing a minimum conductance for the flow to flush the dead zone. Such a lumen 320, controlled by the design length and diameter, can provide a constant flow rate for the fluid, thus allowing a small bypass flow. FIG. 3A shows a forward flushing flush flow 324 through the lumen 320. FIG. 3B shows a backward flushing flow 326 (retraction of flushing flow) through the lumen 320. The direction of blood flow 328 is shown using the dashed lines in FIGS. 3A-3B. In both FIGS. 3A and 3B, the fluid flowing with the minimum conductance can serve to flush the dead zone proximate to the component 321, thereby preventing or minimizing undesired thrombus formation.

4A-4B illustrate another exemplary additive minimum conductance system in accordance with the principles herein. 4A-4B, rather than the extra lumen below the additional minimum conductance component (shown in FIGS. 3A-3B), includes a component (such as, but not limited to, a balloon) on the shaft of the device. 421 illustrates an exemplary additional minimum conductance system that includes one or more holes or orifices 430 just proximal to 421. In these exemplary systems, a small portion 424 of the flow that the device directs towards its distal tip leaks through one or more holes (or orifices) 430 before reaching the occlusion. FIG. 4A also shows the direction of blood flow 428. FIG. 4A shows an example when the value of pressure Pb is smaller than pressure Pa, in which case a backward flushing flow occurs (shown as flow 424). FIG. 4B shows an exemplary additive minimum conductance system for the situation where Pb is sufficiently larger than Pa, which causes a forward flushing flow 426.

FIG. 4C illustrates another exemplary additive minimum conductance system in accordance with the principles herein. The exemplary additional minimum conductance system includes an additional minimum conductance component (spring driven membrane 440) that includes one or more holes (or holes) 431. One or more holes (or holes) 431 are used to control fluid flow and provide minimum conductance. In the exemplary additive minimum conductance system of FIG. 4C, membrane 440 is shown in cross section. However, the membrane 440 includes one or more substantially solid membrane portions that are symmetrically deployed about the device shaft (similar to an umbrella deployment). FIG. 4C also shows the direction of blood flow 428 and a small portion 442 of the fluid flow that has leaked through one or more holes (or holes) 431 of the additional minimum conductance component.

4D(i) and 4D(ii) illustrate another exemplary additive minimum conductance system in accordance with the principles herein. The exemplary system of FIG. 4D(i) includes a multi-lobe soft balloon (or balloon of other structure) 450, which is between the lobes of the balloon in sealing the vasculature. Includes gaps and provides minimum conductance. In various examples, a multi-lobe soft balloon (or other structured balloon) 450 may be formed having two, three, or more lobes. FIG. 4D(ii) shows a cross-sectional view (through line A-A′ shown in FIG. 4D(i)) of a different example of a multi-lobe soft balloon (or other structured balloon) 450. By way of non-limiting example, an additive minimum conductance system may include a two-lobe soft balloon (or other two-lobed structure balloon) 455 that includes a gap 460, or a three-lobe that includes a gap 470. A soft balloon (or other three-lobe structure balloon) 465 may be included.

5A(i)-5C illustrate another exemplary additive minimum conductance system in accordance with the principles herein. In the exemplary system of FIG. 5A, a biasing valve 550 is used to add directional control of flushing flow to minimum conductance. Thus, the directivity can cause a fixed constant flow in the direction supported by the pressure differential across the means. As an example, the pressure difference in the vasculature may change sign depending on the change in blood pressure in the tributary of the infusion point due to each heartbeat, ie, change from a positive pressure value to a negative pressure value based on the pressure fluctuation of systole/diastole. It can be anything. The exemplary additive minimum conductance system turns the flushing flow “on” for only a portion of the heartbeat cycle based on the sign (ie, direction) of the pressure difference, thereby “fixed average” rather than “fixed constant” minimum conductance. It may be arranged such that a minimum conductance can be achieved.

FIG. 5A(i) illustrates an exemplary additive minimum conductance system that includes a biasing valve 510 in the lumen of a catheter lumen that includes a component 521 (such as but not limited to a soft balloon). The parameters P _in and P _out are pressure values inside and outside the lumen proximal to the soft balloon 521. In this example, the distal region is the region where the flow rate and pressure of the flow injected through the lumen and through the distal tip is predominant. In general, when P _out is driven by the heart, the value of P _out has a cycle similar to a heartbeat, reaching local maxima and minima in each cycle. 5A(ii) illustrates an exemplary biasing valve that may be implemented with the exemplary system of FIG. 5A(i). FIG. 5A(ii) illustrates an example attached to a portion of a shaft of a catheter having a hole that connects the inner lumen of the shaft to the outside and a plastic flap that is secured to the hole at least one side larger than the hole. A typical biasing valve 510 is shown. The exemplary biasing valve has a positive pressure differential (pressure on the inside of the shaft that is greater than the pressure on the outside) that causes the flexible plastic flap to open, allowing fluid to flow outwards and negative pressure. The differential (pressure on the inside of the shaft, which is lower than the pressure on the outside) is configured to close the flexible plastic flap, seal against the edge of the hole and block the inward flow of fluid. ..

FIG. 5B illustrates an exemplary additive minimum conductance system that includes a biasing valve 532 coupled to component 521. Biasing valve 532 includes a flap configured to open and allow fluid flow out of the central lumen of the infusion member, but not into the lumen. That is, when the value of the pressure P _b is lower than the pressure P _a, Tsukezeiben 532 to allow flow 534, which occurs during a particular time interval of the heartbeat cycle. FIG. 5B shows a small portion 534 of the flow through the flap of the biasing valve 532 and the direction 538 of the blood flow. In this example, only a small portion of the blood infused into the body from the extracorporeal circuit is used to flush the dead zone (ie, flow 534 through the energizing valve).

FIG. 5C illustrates an exemplary added minimum conductance system that includes a flap that acts as a biasing valve 540 at the end of the bypass lumen 542. The lumen 542 has a discontinuous length l and is disposed below the component 521 along the shaft of the injector member, similar to the additional minimum conductance system shown in FIG. 3A or 3B. .. The action of the biasing valve 540 and bypass lumen 542 are combined to provide a minimum conductance for the flow to flush the dead zone (or low flow zone). FIG. 5C shows a small portion 544 of flow through the flap of the biasing valve 540 and the direction 548 of blood flow. The flap of the biasing valve 540 can be attached to either the proximal or distal end of the bypass lumen 542, which allows the flushing flow direction to be selected by design. That is, if a flap configured to only allow outward fluid guidance is attached to the proximal end of lumen 542 (as shown in FIG. 5C), distal infused blood will regurgitate. And flush. When the flap is attached to the distal end of lumen 542, normal blood flow from the tributaries flushes forward and mixes with the infused blood at the vessel infusion point. The actuating valve can be configured to allow only one-way flow, so the detailed actions are P _b (pressure before lumen 542) and P _a (pressure after lumen 542). Partly explained by the applied pressure difference between and. This exemplary implementation shows that the values of pressures P _a and P _b are close enough so that the change in P _b from the systolic/diastolic pressure change with heartbeat causes a particular time interval in each cardiac cycle. It may be beneficial if the biasing valve is open therein.

In accordance with the principles herein, an exemplary additive minimum conductance component, or an exemplary system including an additive minimum conductance component, can be used to provide selective temperature therapy. The exemplary additional minimum conductance component can be coupled to any system configured to apply selective temperature therapy. In any exemplary implementation, additional minimum conductance components in accordance with the principles herein may be used in place of conventional occlusion components. The additional minimum conductance component can be disposed proximate the distal tip of at least one injector member of the system for applying selective temperature therapy. As a non-limiting example, additional minimum conductance components in accordance with the principles herein are disclosed in US Pat. No. 7,789,846 B2, or International (PCT) Patent Application No. PCT/US2015/033529. Etc. can be coupled to any system in the art for applying selective temperature therapy.

In any of the examples herein, the additional minimal conductance component can be formed to have an atraumatic surface, a hydrophilic coating, or a drug coating, or any combination thereof.

FIG. 6A illustrates an exemplary controlled flow splitting system of the present disclosure. The exemplary controlled flow splitting system includes a first pressure sensor 610 and a second pressure sensor 612. The first pressure sensor 610 can be disposed proximate to the tip of the catheter's injector member 614 and the second pressure sensor 612 can be pre-defined measured from the tip (or from the pressure sensor 610). Can be disposed on the injector member 614 proximal to the operator by a distance (Δ). As a non-limiting example, the predefined separation distance (Δ) can be about 2 cm, about 5 cm, about 8 cm, about 12 cm, about 15 cm, about 20 cm, about 25 cm, or about 30 cm. In various non-limiting examples, one or both of pressure sensors 610 and 612 may be a silicon-based sensor (with electronic (wired) readout) embedded in the catheter wall or a lumen in the catheter wall. The fibers within can be used to implement as a fiber optic based pressure sensor that provides readout to a suitable computing interface at the proximal end of the catheter. In another exemplary implementation, one or both of pressure sensors 610 and 612 include a simple wall lumen filled with an incompressible fluid having a distal opening in the position shown in FIG. 6A, and a lumen. It is configured to use an external pressure sensor attached to a fluid connector at the proximal end of the catheter to measure static or low frequency pressure induced by the fluid column. Pressure sensor 610 may be configured to measure pressure proximate the tip (P _tip ) and pressure sensor 612 may be configured to measure pressure proximate the injector member 614 (P _b ). You can FIG. 6A also shows an example of the direction of blood flow with a flow rate F _b around the catheter and an infused blood flow with a flow rate F _{tip at} the _tip of the injector member.

As also shown in FIG. 6A, the catheter can be coupled to a flow source 616 of the extracorporeal system. In an exemplary implementation, the fluid may be volume flow driven rather than pressure driven. When fluid is injected into the vasculature through the tip (F _tip ), it mixes with fluid from the upstream (F _b ) and flows through the downstream conductance G _tip . Upstream flow passes through the conductance G _b shown in FIG. 6A, which occurs in the space between the artery (or vein) wall and the catheter. Directly measuring or predicting the value of conductance G _b can be difficult. Even if pressure sensors 610 and 612 are provided to measure P _b and P _tip , it may be difficult to measure F _b directly when G _b is unknown. Exemplary systems and methods according to the principles herein may be used to determine the value of G _b .

In the example, a flow source can be used to control the volume flow rate. Exemplary flow sources can be, but are not limited to, positive displacement pumps, syringe pumps, or rotary pumps.

In the example, a flow source can be used to control the flow rate of the infused fluid at the distal tip to flow as a series of volume impulses. In this example, a series of volume impulses can be modeled according to a step function. The flow source is activated based on a first signal from the pump, or a pump executing instructions from the processing unit of the console to deliver each impulse of the series of impulses, and a second signal from the console. Can be a pump that continuously delivers impulses of a step function until the pump stops working by the signal

In other examples, the flow rate is controlled so that the fluid flows according to other types of functional forms such as, but not limited to, sinusoidal, sawtooth, or other forms of periodic functional forms. For this purpose, a flow source can be used.

In any of the examples herein, a flow source can be used to control the flow rate to establish a flow pattern. As described above, the flow pattern may be based on any waveform or other type of functional form such as, but not limited to, a sinusoidal function form, a sawtooth function form, or other form of periodic function form. Good.

In a non-limiting example according to the principles of FIG. 6A, the injector member is coupled to two pressure sensors, which injector member is driven by an external flow control means to provide a proximal external conductance and a distal external conductance. The value can be measured or calculated. The exemplary system can infer the flow around the injector member of the catheter from data indicative of pressure measurements.

A controlled flow splitting system is provided to determine two conductances, including the system shown in Figure 6A. The first conductance, called the proximal conductance (G _b ), is the conductance in the vascular space outside the catheter between the planes defined by the two pressure sensors 610 and 612. The second conductance, called the distal conductance (G _tip ), is the conductance from the tip to the blood return to the core system (or ground in the sense of flow). Both of these conductances generally cannot be inferred without measurements, since data indicating the size and shape of the local vasculature are used in the calculations. For G _tip, Kanmyaku structural floor status, and / or data indicating the amount of the damage is used in the calculation. Both of these conductance values represent a measure of the local state of vasodilation/vasoconstriction in the patient, so knowing them can provide clinical benefit. Using pressure sensors 610 and 612 to measure P _b and P _tip , if the conductance between them is a controlled conductance, such as the additive minimum conductance described above, then F _b = G _b a _(P b _{-P tip)} can be evaluated flow using. In an exemplary implementation where the calculation of G _b includes data representing the surface of a vein or artery, it may not be possible to determine G _b in advance. Generally, G _tip cannot be determined prior to surgery or other medical procedure involving placement of an infusion member.

Exemplary systems and methods for calculating both the G _b and G _tip in situ to a patient or in other medical procedures during surgery, are provided herein. Using the linear approximation, flow balancing around the distal tip of the infusion member can be expressed using the following two equations.
(1). ． ． ． _{F b = G b (P b} - P tip)
(2). ． ． ． (F _b + F _tip ) = G _tip (P _tip )
The value of F _tip can be set from a pump (such as, but not limited to, flow source 616). The example system of FIG. 6A can be used to measure the values of pressure P _b and pressure P _tip . Using these values, the formula can be summarized as follows:
(3). ． ． ． _{G tip = F tip / P tip} + G b (P b -P tip) / P tip
Here, G _tip and G _b are unknown. During surgery or other medical procedures that use an infusion member to return blood to the body, the first infusion stream at time T ₀ can be used as the F′ _tip (as a non-limiting example, about 250 ml). /Min). At time T ₁ , its value of flow may be changed to F″ _tip (approximately 275 ml/min, a 10% increase as a non-limiting example). These non-limitation of flow at times T ₀ and T ₁ . Exemplary values can be chosen to be within the desired clinical range for the particular anatomy of the infusion point and the particular clinical application, using the exemplary system of Figure 6A. , the pressure _{P b} and a pressure _{P tip} values at time _{T 0} (P _'b and P' _tip), as well as to measure the pressure _{P b} and a pressure _{P tip} value (P _"b and _{P" tip)} at time _{T 1} It is possible to use four different values of pressure and two different values of injection flow in Eq. (3), namely F′ _tip , P′ _tip , P′ _{b at} time T ₀ and time. By introducing F″ _tip , P″ _tip , and P″ _b in T ₁ , two equations (2) are generated, and each two (2) are unknown. These equations can be used to calculate the values of G _b and G _tip . It will be readily apparent to those skilled in the art that equations (1), (2), and (3) are non-limiting examples of equations for vascular region flow, conductance, and pressure. Other formulas may be applicable, including more complex versions of the formula. For example, solving equations where the conductance is not a function of pressure but is itself a function of pressure using repeated pressure measurements at different values of the applied flow F _tip , establish more equations, linear, Or it may allow a solution in the form of conductance (G) that is a function of quadratic or higher pressure.

As described herein, the fluid infused at the distal tip may include, but is not limited to, a step function or sinusoidal, sawtooth, or other form of periodic functional form. A flow source can be used to control the flow rate to flow according to other types of functional forms. In another example, the flow rate can be modeled based on the measured response function with fluid flow and the applicable functional form of the solution.

Exemplary systems and methods for calculating both the G _b and G _tip in situ relative to the patient's long surgery or in the other medical procedure is provided herein. As a non-limiting example, such lengthy surgery (or other medical procedure) can last from approximately hours to days. An exemplary method is to have a gradual change in F _tip (ie, discontinuity in value from baseline) during a short time interval (t ₁ ) during a surgical or other medical procedure in regular repeating cycles. Change) may be applied. As a non-limiting time, a step change may be applied to F _tip for the first 5 minutes of each hour of surgery or other medical procedure (ie, t ₁ =5 minutes). At the end of time interval t ₁ , the value of F _tip is returned to the baseline value. This exemplary method of modifying the value of F _tip is used to measure G _b and G _tip at each time during a long surgery or other medical procedure using the method described herein. can do. These exemplary systems and methods have clinical application in monitoring vascular status (vasodilation/vasoconstriction) or in the process of thrombus formation, or in detecting the time of thrombolysis.

Another exemplary clinical application of the exemplary system and method is as follows. During surgery or other medical procedure, the calculated values of G _b and G _tip are used to determine the amount of flow F _b flushing the space proximal to the tip from the measured pressures P _b and P _tip. Can be judged. If the flow F _b is outside the desired value range, then F _tip may be adjusted to adjust F _b .

Another clinical application of the system and method is the determination of the heat capacity of blood applied to tissue. During surgery or other medical procedure, F _b and F _tip may mix in the zone distal to the _tip . If the blood flow F _b is at a first temperature and the infused blood flow F _tip is at a second temperature different from the first temperature, the heat capacity of the blood applied to the tissue in the distal zone is directly It can be calculated and the temperature regulation of the infused blood can be used to compensate for warm or cold blood flow F _b . Alternatively, the flow F _b: a ratio of F _tip, and by adjusting the temperature difference of them controlled rewarming process may be performed. The exemplary methods for measuring G _b and G _tip described herein can be applied one or more times during surgery or other medical procedures. The method can be generalized to use more than one step change in F _tip , in which case the operator measures the values of G _b and G _tip and those values are given by the formula ( It is possible to determine how it changes outside the linear approximation of 1 to 3). An operator can perform an exemplary method according to the principles herein, for example, by directly setting F _tip or by recording sensor readings and performing calculations using a computing device. it can. In another exemplary implementation, the computing device or system herein can include at least one processing unit, which processing unit is herein for measuring the values of G _b and G _tip . Are programmed to execute processor-executable instructions for causing the controller of the exemplary system to automatically implement the measurement routines described in. The exemplary system sets a nominal value of F _tip and G at desired time intervals such as, but not limited to, every 30 minutes, or every 45 minutes, or every 60 minutes, or other time intervals. _It may be configured to allow a user to execute processor-executable instructions for making automatic measurements of _b and _Gtip . In any of the examples herein, the computing device can be a console.

FIG. 6B illustrates an exemplary controlled flow splitting system according to the principles herein. The exemplary system includes two pressure sensors for use with a concentric cylinder two-port catheter for supporting independent local extracorporeal loops. As shown in FIG. 6B, two pressure sensors 610' and 612' are coupled to an insert member 614 which is part of a concentric shaft type extracorporeal circuit access catheter. In the example, the outer shaft 618 supplies blood to the extracorporeal circuit 618 and the inner shaft 614 acts as an infusion member to return the blood to a location on the body. FIG. 6B also shows a dashed line 615 of blood flow exiting the extracorporeal circuit and a dashed line 617 of blood flow around the catheter (Fb). As a non-limiting example, US Pat. No. 7,704,220 and US Pat. No. 7,789,846 are concentric that can be implemented in one or more exemplary systems in accordance with the principles herein. An example of an extracorporeal access catheter is disclosed.

6C and 6D illustrate an exemplary system that can be used to calculate the value of conductance in the region of the vasculature proximate to the heart in accordance with the principles herein. In the examples of FIGS. 6C and 6D, the exemplary system is shown disposed in the region of the aortic arch. As shown in FIG. 6C, the exemplary system includes pressure sensors 610 and 612 coupled to catheter member 620. In this example, pressure sensor measurements can be used to calculate conductance, as described herein. In this example, the pressure measurements can be used to calculate conductance in response to the exemplary method described above for calculating both G _b and G _tip in situ. In the example of FIG. 6C, fluid flow can be introduced from the distal tip of catheter member 620. FIG. 6D is another exemplary system similar to FIG. 6C, except that catheter 620 includes a proximal port 622 that allows fluid flow from a more intermediate region of catheter member 622. There is.

In any of the exemplary systems, methods, devices, and apparatus herein, the fluid infused through the infuser member is mixed with fluid (external fluid) passing through the external space around the catheter or device. Good. When fluid streams are mixed, they form a mixed fluid in the region distal to the injection point (also referred to herein as mixed distal flow). When a known concentration (mg/ml or other unit of mass/volume) of drug or agent is added to the infusion fluid, the concentration of the drug or agent in the distal mixing fluid is the ratio of the flow rate of the external fluid to the infusion fluid. Unknown unless known. The exemplary system described herein can be used to set the external conductance (additional minimum conductance component) or to quantify the external conductance (controlled split flow system). The flow rate of the external fluid can be measured or calculated based on the conductance data. With the calculated value of the external fluid flow rate and the infusion flow rate set by the pump system (or other system) coupled to the infuser member, the concentration of the drug or agent added to the infusion fluid can be measured distally. It can be adjusted to achieve the desired concentration of drug in the fluid mixture.

In any example herein, a drug or agent can be any substance used to diagnose, treat, treat, or prevent a disease. For example, the drug or agent may include an electrolyte solution, nanoparticles, biological agent, small molecule, large molecule, polymeric material, biopharmaceutical, or any other drug or agent that can be administered to the bloodstream. it can.

An exemplary system according to the principles herein can be used to provide at least two zones of selective temperature therapy. The exemplary system includes an extracorporeal circuit. An exemplary extracorporeal circuit includes an injector member that includes a distal tip disposed at a vessel location and an additional minimum conductance component disposed proximate to the distal tip. The exemplary system includes a first port for drawing blood from the body, a second port for returning blood to the body, and a first port for drawing blood from the first port to the second port. A first pump disposed between the first port and the second port, a bifurcating section positioned between the first pump and the second port, and an injector member coupled to the bifurcating section. A third port located external to the body and a second pump located between the bifurcation section and the third port. The second pump can be configured to control the flow rate out of the bifurcation section and into the injector member through the third port. The exemplary system also includes a first heat exchanger disposed between the first port and the second port and a second heat exchanger disposed between the second pump and the injector member. And a heat exchanger. The first heat exchanger can be configured to set the temperature of the blood injected into the second port to the first temperature level. The second heat exchanger can be configured to set the temperature of the blood injected into the injector member to a second temperature level that is different than the first temperature level. The first heat exchanger can be arranged between the branch section and the first port or between the branch section and the second port.

An exemplary system for providing at least two zones of selective temperature therapy may include an occlusion component disposed adjacent the distal tip of the injector member, or an additional minimum conductance component. it can.

Another exemplary system for providing at least two zones of selective thermotherapy according to the principles herein includes an extracorporeal circuit that includes an injector member with a distal tip positioned in a vascular position. be able to. The exemplary system can further include a controlled flow splitting system proximal of the distal tip. The controlled flow splitting system comprises a first sensor for measuring flow proximate a distal tip of at least one injector member, a second pressure sensor for measuring a second pressure, and A second pressure sensor disposed proximally from the distal tip a distance greater than or approximately equal to the diameter of the vasculature. In other examples, the separation distance may be greater than or approximately equal to three, five, or ten times the diameter of the vasculature. In another example, the separation distance may be greater than about 1.0 cm proximally from the distal tip. The exemplary system also includes a first port for drawing blood from the body, a second port for returning blood to the body, and a first port for drawing blood from the first port to the second port. A first pump disposed between the first port and the second port, a bifurcation section positioned between the first pump and the second port, and an injector coupled to the bifurcation section A third port is located external to the member and a second pump is located between the bifurcation section and the third port. The second pump can be configured to control the flow rate out of the bifurcation section and into the injector member through the third port. The exemplary system also includes a first heat exchanger disposed between the first port and the second port and a second heat exchanger disposed between the second pump and the injector member. And a heat exchanger. The first heat exchanger can be configured to set the temperature of the blood injected into the second port to the first temperature level. The second heat exchanger can be configured to set the temperature of the blood injected into the injector member to a second temperature level that is different than the first temperature level. The first heat exchanger can be arranged between the branch section and the first port or between the branch section and the second port.

An exemplary system for providing at least two zones of selective temperature therapy may include an occlusion component disposed adjacent the distal tip of the injector member, or an additional minimum conductance component. it can.

FIG. 7A shows a schematic diagram of an exemplary three-port extracorporeal circuit for providing at least two zones of selective temperature therapy according to the principles herein. As a non-limiting example, an extracorporeal circuit may be implemented to control blood flow to the core and associated local tributaries with independent flow and temperature controls. In the non-limiting example of FIG. 7A, the extracorporeal system 700 is a three-port, two-zone extracorporeal circuit in which a main static arterial (VA) extracorporeal loop 710 removes blood from the body via a first port 711. , Pump 712 and oxygenator/heat exchanger 714 are used to return blood via second port 715. The exemplary system draws a controlled volumetric flow of blood from the main circuit, located in a tributary 718 of the main loop, through a separate heat exchanger 720, a third port 721, and a distal injector member 722. A positive displacement or volume driven pump 716 can be included to infuse it into a localized area 724 of the body. In a non-limiting example, tributary 718 can be a local perfusion hypothermic tributary. The non-limiting exemplary system of FIG. 7A allows two independently controlled temperature zones to be established within the body when deployed with an appropriate zone temperature sensor. In another example, depending on the user's desire to oxygenate the blood of the infuser member, a tributary 718 may be coupled to the main loop either before or after the main loop oxygenator 714. You can In these examples, the system is used to apply local hypothermia through a distal injector member, such as those disclosed in International (PCT) Patent Application No. PCT/US2015/033529. In some cases, the lack of concentric cylinder outflow on the injector member may increase the induced cooling of the catheter of that member to the artery in which it is located. This effect may require some additional warming of the main circuit loop to achieve an equivalent temperature goal in the body zone that it is desired to control.

FIG. 7B illustrates another exemplary extracorporeal circuit for providing at least two zones of selective temperature therapy according to the principles herein. Similar to FIG. 7A, the extracorporeal circuit system 700 ′ of FIG. 7B removes blood from the body via the first port 711 and uses a pump 712, an oxygenator 713, and a heat exchanger 714 to provide a second Main VA extracorporeal loop 710 which returns it via port 715 of In a non-limiting example, oxygenator 713 and heat exchanger 714 can be a combined unit. The exemplary system 700 ′ also draws a controlled volumetric flow of blood from the main circuit, located in the tributary 718, through a separate heat exchanger 720, a third port 721, and a distal injector member 722. Includes a positive displacement or volume driven pump 716 for infusing it into a localized area of the body. In the exemplary extracorporeal system 700', the injector member is a closure means, an additional minimum conductance component (according to any of the examples herein, including any of FIGS. 3A-5C), or an injector member. A pressure sensor pair (according to any of the examples herein, including FIG. 6A or FIG. 6B), or both a pressure sensor pair and a closure means, or both a pressure sensor pair and an additional minimum conductance component. Can be included. In the non-limiting exemplary system of FIG. 7B, injector member 722 includes both an additional minimum conductance component 726 and a coupled pressure sensor pair 728. In the example of FIG. 7B, the main loop oxygenator 714 is positioned in front of the local infuser tributary 718, so that the locally infused blood is oxygenated.

FIG. 7C illustrates another exemplary extracorporeal circuit for providing at least two zones of selective temperature therapy according to the principles herein, the extracorporeal circuit being configured as described in connection with FIG. 7B. It contains components similar to elements. However, in the extracorporeal system 700″ of FIG. 7C, the main loop oxygenator 713 is positioned along the loop after the local infuser tributary, so that the locally infused blood is not directly oxygenated. In a limiting example, oxygenator 713 and heat exchanger 714 can be a combined unit.

Any non-limiting exemplary system of FIGS. 7A-7C can be coupled to a region of the body to provide temperature measurements of two independently controlled temperature zones within the body. A temperature sensor can be included. For example, at least one temperature sensor may be disposed or otherwise coupled to the area perfused by the second port, wherein the at least one temperature sensor is local to the body being perfused by the distal injector member. It may be disposed in the area or otherwise coupled. At least one temperature sensor disposed or otherwise coupled to the area perfused by the second port measures an average core body temperature and/or an average system temperature of a portion of the body. Can be configured. At least one temperature sensor disposed or otherwise coupled to a localized area of the body perfused by the distal injector member is configured to measure the temperature of the localized area.

Any non-limiting exemplary system of FIGS. 7A-7C can include a temperature sensor coupled to at least one of the heat exchangers.

Other non-limiting exemplary systems according to the principles of FIGS. 7A-7C include but are not limited to dialysis, oxygenation, purification, pharmacological manipulation, photolysis, or other procedures that may be useful for blood. Other procedures, not limited to, can be configured to perform on the blood in an extracorporeal loop. One or more of these procedures may be performed in either the main loop or a tributary, or (a condition in which the amount or number of one or more of the procedures performed in the loop or a tributary is different). May be done both.

In the non-limiting example of FIGS. 7A-7C, the main loop is described as a VA loop. However, in other exemplary implementations, the main loop can be a venovenous (VV) loop rather than a VA loop. In an exemplary VV loop, blood is drawn from the venous side of the vasculature, typically from the iliac vein or inferior vena cava, and typically returned to the vena cava at a higher or closer to the heart. .. In another example, the VV may be performed with a single perforation in the thigh and a single dual lumen catheter may be used to provide both blood output and return for the VV loop, each catheter Can be deployed using a single lumen.

An exemplary system in accordance with the principles herein may include one or more control consoles. The exemplary console receives inputs representative of desired settings for one or more of the exemplary extracorporeal system main loop and/or local tributary pumps, heat exchangers, and/or oxygenators. Can include one or more user interfaces configured to. Exemplary consoles allow one or more of pumps, heat exchangers, and/or oxygenators to make changes to different operating settings and/or maintain particular operating settings over a period of time. One or more processing units for executing the processor-executable instructions of the. In any example, the input may be received directly from a user or from another computing device at one or more user interfaces. An exemplary console can include at least one memory for storing processor-executable instructions that may be implemented using one or more processing units. The example console may provide data representative of system settings and/or any measurement data obtained based on performing one or more procedures using the example system coupled to the console, It may be configured to store and/or transmit.

FIG. 8A illustrates an exemplary extracorporeal circuit system 800 coupled to a console 802 according to the principles herein. Similar to FIG. 7B, the extracorporeal system 800 of FIG. 8A draws blood from the body via a first port 811 and uses a pump 812, an oxygenator 813, and a heat exchanger 814 to a second port 815. Includes a main VA extracorporeal loop 810 that returns blood through the VA. In a non-limiting example, oxygenator 813 and heat exchanger 814 can be a combined unit. The exemplary system 800 also draws a controlled volumetric flow of blood located in the tributary 818 from the main circuit, through a separate heat exchanger 820, a third port 821, and a distal injector member 822. Includes a positive displacement or volume driven pump 816 for injecting into a localized area of the body. Also, similar to the non-limiting example system of FIG. 7B, the injector member includes an additional minimum conductance component 826 and a pressure sensor pair 828. In the example of FIG. 8A, the console 802 is coupled to a positive displacement or volume driven pump 816 located in the tributary 818, and a pressure sensor pair 828. In other examples, console 802 may be coupled to different components of the system, including any one or more of the exemplary system pumps, heat exchangers, and/or oxygenators.

The non-limiting exemplary system of FIG. 8A may include a temperature sensor that may be coupled to a region of the body to provide temperature measurements of two independently controlled temperature zones within the body. it can. For example, at least one temperature sensor may be disposed or otherwise coupled to the area perfused by the second port, wherein the at least one temperature sensor is local to the body being perfused by the distal injector member. It may be disposed in the area or otherwise coupled. At least one temperature sensor disposed or otherwise coupled to the area perfused by the second port measures an average core body temperature and/or an average system temperature of a portion of the body. Can be configured. At least one temperature sensor disposed or otherwise coupled to a localized area of the body perfused by the distal injector member is configured to measure the temperature of the localized area.

In the example, console 802 can be configured as an operating console. In this example, the operating console includes a water cooler/heater to drive the heat exchanger and a graphical user interface configured to display user instructions to perform the operating steps of the operating sequence. be able to. A graphical user interface of console 802 controls the temperature of blood perfused by the second port to adjust the temperature readings reported by the at least one temperature sensor to stay within the core body target range. , To cause the extracorporeal circuit to perform, and to control the temperature of the blood infused into the local region so that the at least one temperature sensor can report a temperature measurement within the target region temperature range. May be configured to implement an operating sequence for

The exemplary console 802 may be configured to automate the performance of G _b and G _tip measurements using the controlled flow splitting system described herein. Based on the input received, the console responds to the principles of any of the examples described herein, recording data indicative of internal flow and pressure values on the infusion member. In order to facilitate or enable the method of measuring the proximal and distal conductances of the injector member to be automatic, instructions for controlling the amount of infusion flow may be executed by the processor. .. Such an exemplary console 802 can be configured to automate a controlled flow splitting system, where the controlled flow splitting system is coupled to a complete extracorporeal loop, or such as in the example of FIG. 6A. It applies to an injector member coupled to another catheter system having, but not limited to, an extracorporeal volumetric flow source.

FIG. 8B illustrates another exemplary system 850 coupled to a console 852 according to the principles herein. The exemplary system 850 includes a flow control source 860 and a reservoir 862. As a non-limiting example, the exemplary flow control source 860 and reservoir 862 can be, but are not limited to, a syringe or syringe driver. The exemplary system 850 also includes a distal injector member 872 coupled to a localized area of the body. The injector member 872 includes an additional minimum conductance component 876 and a pressure sensor pair 878. In the example of FIG. 8B, console 802 is coupled to flow control source 860 and pressure sensor pair 878. In the example of FIG. 8B, the flow control source 860 and reservoir 862 are used to establish the two Ftip settings of the controlled flow splitting system (according to any of the examples described above). As a non-limiting example, a setting based on a command received at the console may be such as first bleeding into the reservoir at 50 ml/min for 2 minutes, then waiting for 2 minutes, then at 50 ml/minute for 2 minutes. May be returned. In this non-limiting example, this establishes Ftip=−50 ml/min, Ftip=0, and Ftip=+50 ml/min. Based on the input received at console 852, such as from a user or another computing device, the instructions may be executed to perform any other desired procedure depending on the settings specified in the input.

An exemplary system in accordance with the principles herein may include one or more controllers for controlling fluid flow. For example, one or more controllers may be coupled to the infusion member to control the flow of fluid out of the distal tip of the infusion member.

An exemplary system according to the principles herein can include a console. FIG. 9 shows an exemplary console 905 that includes at least one processing unit 907 and memory 909. An exemplary console may be, for example, a desktop computer, laptop computer, tablet, smartphone, server, computing cloud, combinations thereof, or any other capable of electronic communication with a controller or other system in accordance with the principles herein. Can include any suitable device. Exemplary processing unit 907 may include a microchip, processor, microprocessor, dedicated processor, application specific integrated circuit, microcontroller, field programmable gate array, any other suitable processor, or combinations thereof. However, it is not limited to these. Exemplary memory 909 includes random access memory, including but not limited to hardware memory, non-transitory tangible media, magnetic storage disks, optical disks, flash drives, computer device memory, DRAM, SRAM, EDO RAM, etc. Other types of memory, or combinations thereof, but are not limited thereto.

In the example, the console can include a display unit 911. The exemplary display unit 911 includes an LED monitor, an LCD monitor, a television, a CRT monitor, a touch screen, a computer monitor, a touch screen monitor, a screen of a mobile device (such as but not limited to a smartphone, tablet, or ebook). Alternatively, it may include, but is not limited to, a display and/or any other display unit.

10A-10B are exemplary flow-dividing systems, or exemplary systems that can be implemented using at least two pressure sensors coupled to a catheter member, according to the principles herein. Here's how to do it. One or more of the steps of FIGS. 10A-10B may be performed using the controller based on commands or other signals from the processing units executing the instructions stored in memory.

FIG. 10A shows controlling the flow of fluid injected at the distal tip of the injector member into a predetermined flow pattern over a time interval T (step 1002 ), including a first pressure sensor and a second pressure sensor. Recording a pressure measurement over a time interval T (step 1004) using data indicating the pressure measurement and a predetermined flow pattern to use a proximal external conductance or distal external at the distal tip. Calculating at least one of the conductances (step 1006). The distal tip can be part of the injector member of the extracorporeal circuit or part of the catheter member. In an example, the flow pattern can be controlled using an infusion flow source. In the example, the infusion flow source can be a pump.

FIG. 10B illustrates another exemplary flow splitting system, or another exemplary system that can be implemented using at least two pressure sensors coupled to a catheter member, according to the principles herein. Show the method. In step 1052, the flow of blood injected at the distal tip of the injector member (or catheter member) is controlled to a first constant flow rate for a first time interval (T _A ). At step 1054, each of the first pressure sensor and the second pressure sensor records at least a first pressure measurement value (P _1A and P _1B ) during a first time interval (T _A ). used. In step 1056, the flow of blood injected at the distal tip of the injector member is controlled to a second constant flow rate that is different from the first constant flow rate for a second time interval (T _B ). In step 1058, each of the first pressure sensor and the second pressure sensor to record at least a second pressure measurement value (P _2A and P _2B ) during a second time interval (T _B ). Is used. In step 1060, the data indicating the first pressure measurement, the second pressure measurement, the first constant flow rate, and the second constant flow rate are used to determine the distal tip of the injector member (or catheter member). At least one processor of the processing unit is used to calculate at least one of the proximal or distal outer conductance at.

In an example, the exemplary console can cause the display unit to display a proximal external conductance, a distal external conductance, or both, based on the calculation.

In the example, the processing unit comprises a proximal or distal outer conductance over a third time interval (T _C ) that is later than the first time interval (T _A ) and the second time interval (T _B ). At least one of the predictions may be calculated.

FIG. 11 is a block diagram of an exemplary computing device 1110 that may be used to perform operations in accordance with the principles herein. In any of the examples herein, computing device 1110 can be configured as a console. For clarity, FIG. 11 also revisits the various elements of the exemplary system of FIG. 9 and provides further details regarding them. Computing device 1110 may include one or more non-transitory computer-readable media for storing one or more computer-executable instructions or software for implementing the examples. A non-transitory computer-readable medium is one or more of a hardware memory, a non-transitory tangible medium (eg, one or more magnetic storage disks, one or more optical disks, one or more flash drives), etc. Can be included, but is not limited to. For example, memory 909 included in computing device 1110 may store computer readable or computer executable instructions or software for performing the operations disclosed herein. For example, the memory 909 performs various operations of the disclosed operations (eg, having the controller perform flow control, record pressure sensor measurements, or perform calculations). A software application 1140 configured as described above may be stored. Computing device 1110 is configurable and/or configured to execute computer-readable or computer-executable instructions or software stored in memory 909 and other programs for controlling system hardware. Programmable processor 907 and associated core 1114, and optionally one or more additional configurable and/or programmable processing devices (eg, where the computing device has multiple processors/cores), For example, processor 1112' and associated core 1114' may also be included. Processor 907 and processor 1112' may each be a single core processor or a multi-core (1114 and 1114') processor.

Virtualization may be used in the computing device 1110 so that infrastructure and resources within the console can be dynamically shared. The virtual machine 1124 may also be provided to handle processes running on multiple processors such that the process appears to be using only one computing resource instead of multiple computing resources. Good. Multiple virtual machines can be used with a single processor.

The memory 909 may include computer device memory such as DRAM, SRAM, EDO RAM, or random access memory. Memory 909 may also include other types of memory, or combinations thereof.

A user may interact with the computing device 1110 through a visual display unit 1128 such as a computer monitor, which visual display unit 1128 displays one or more user interfaces 1130 that may be provided by the exemplary systems and methods. be able to. Computing device 1110 may include other I/O devices for receiving input from a user, such as a keyboard or any suitable multipoint touch interface 1118, pointing device 1120 (eg, mouse). The keyboard 1118 and pointing device 1120 can be coupled to a visual display unit 1128. Computing device 1110 may include other suitable conventional I/O peripherals.

Computing device 1110 may be a hard drive, a CD-ROM, or other computer readable medium for storing data and computer readable instructions and/or software performing the operations disclosed herein. One or more storage devices 1134, such as, can also be included. The exemplary storage device 1134 may also store one or more databases for storing any suitable information necessary to implement the exemplary systems and methods. The database may be updated manually or automatically at any suitable time to add, delete, and/or update one or more items in the database.

The computing device 1110 may be connected to one or more networks via one or more network devices 1132, such as a local area network (LAN), a wide area network (WAN), or a standard telephone line, LAN or WAN link (eg, 802). .11, T1, T3, 56 kb, X.25), broadband connection (eg ISDN, frame relay, ATM), wireless connection, controller area network (CAN), or any combination of any or all of the above. A network interface 1122 configured to interact with the Internet, including but not limited to various connections, may be included. The network interface 1122 can be a built-in network adapter, a network interface card, a PCMCIA network card, a Cardbus network adapter, a wireless network adapter, a USB network adapter, a modem, or can communicate and perform the operations described herein. It may include any other device suitable for interfacing computing device 1110 to any possible type of network. In addition, computing device 1110 can be a workstation, desktop computer, server, laptop, handheld computer, tablet computer, or can communicate and has sufficient processor power and memory capacity to perform the operations described herein. It may be any other computing device, such as another form of computing device or communication device having.

The computing device 1110 may be any version of the Microsoft® Windows® operating system, different releases of the Unix and Linux® operating systems, any version of the MacOS® for Macintosh computers, Any embedded operating system, any real-time operating system, any open source operating system, any proprietary operating system, or any that can run on the console and perform the operations described herein. Any operating system 1126 can be run, such as any of the other operating systems of. In some examples, operating system 1126 can run in native mode or emulation. In the example, operating system 1126 can run on one or more cloud machine instances.

In a non-limiting example, computing devices according to the principles herein include smartphones, tablet computers (such as, but not limited to, iPhone(R), Android(TM) phones, or Blackberry(R)). , A laptop, a slate computer, an electronic gaming system (such as, but not limited to, XBOX®, Playstation®, or Wii®), an electronic reader (e-reader), and/or It may include any one or more of other electronic readers or handheld computing devices.

In any example herein, at least one method herein may be implemented using a computer program. A computer program, also known as a program, software, software application, script, application or code, is written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages. The computer program can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. The computer program may, but need not, correspond to files in the file system. A program may be stored in a portion of a file that holds other programs or data (eg, one or more scripts stored in a markup language document), or in a single file dedicated to that program. Of course, or may be stored in multiple coordinated files (eg, a file that stores one or more modules, subprograms, or portions of code). The computer program may be deployed to run on one computer or on multiple computers located at one location, or distributed across multiple locations and interconnected by a communications network. May be done.

An exemplary computing device is an application (“App”) for performing functions such as analyzing temperature sensor data, pressure sensor data, and calculating conductance, as described herein. Can be included. In a non-limiting example, App is an *.* for an Android compatible system. apk file or for systems compatible with iOS (registered trademark) *. It can be configured to be downloaded as an app file.

An exemplary console in accordance with the principles herein implements control procedures for operational sequences such as those described in International (PCT) Patent Application No. PCT/US2015/033529, which is incorporated herein by reference. Can be used for. For example, the console can include a display that includes a user interface and a cooler/heater to drive the heat exchanger. The exemplary console includes at least one first temperature sensor positioned to measure the average core body temperature and/or the average system temperature of the portion of the body that is perfused with the second port. , Can be coupled to at least one second temperature sensor positioned to measure the temperature of the local area perfused by the injector member. The user interface is configured to display user instructions for performing the operating steps of the operating sequence. A non-limiting exemplary console is provided for operators to adjust to lower temperatures when temperature bands are set in the device at all stages of operation and the sensor temperature drifts out of the target range during each stage. May include a user interface and computing device defined herein to implement a semi-automatic control procedure. A non-limiting exemplary console automatically adjusts to lower temperatures when temperature bands are set in the device at all stages of operation and the sensor temperature drifts out of the target range during each stage. The system may be configured to include a user interface and computing device defined herein to implement a fully automatic control procedure.

Exemplary systems and methods herein include patients suffering from local or systemic ischemic injury or circulatory injury, such as those described in International (PCT) Patent Application No. PCT/US2015/033529. It can be used to establish and control two different temperature zones of at least a part of the body in order to carry out at least part of the treatment procedure for. An exemplary method is to connect a systemic extracorporeal extracorporeal circuit (SPEC) to the body with a loop placed in the periphery and a local extracorporeal extracorporeal circuit (LPEC) to blood flowing in the vasculature of the body. Binding to a local target area (such as, but not limited to, the brain). The SPEC may include SPEC input and SPEC output flow ports that contact blood flowing within the vasculature, a SPEC pump, and a SPEC heat exchanger. The LPEC can include LPEC input and LPEC output flow ports that contact blood flowing through the vasculature, an LPEC pump, and an LPEC heat exchanger. The LPEC input flow port is arranged to perfuse a local target area of the body. The method comprises locating at least one SPEC sensor for measuring an average core body temperature and/or an average system temperature of a body perfused by SPEC, and measuring the temperature of a local target area perfused by LPEC. Positioning at least one LPEC sensor for measurement, performing an operating step of at least a minimum operating sequence, for recording measurements of at least one LPEC sensor and at least one SPEC sensor, and Implementing a control procedure for independently controlling the blood flow rate and the heat exchanger temperature of each of the SPEC and LPEC. The LPEC can include an injector member that includes a distal tip disposed to contact blood flowing within the vasculature, the LPEC injector member for perfusing a localized target area of the body. It is arranged. The LPEC can include additional minimum conductance components according to the principles described herein, or controlled flow splitting systems, or both. In the example where the LPEC includes a controlled flow splitting system, the LPEC pump can serve as the injection flow source for the controlled flow splitting system.

The LPEC input flow port can be placed in contact with either the left common carotid artery, the right carotid artery, or the artery downstream of one of these locations.

In an example, the control procedure causes the SPEC to control the temperature of blood infused by the SPEC to adjust the temperature readings reported by the SPEC temperature sensor to stay within the target core body temperature range. And allowing the LPEC to control the temperature of the blood infused into the target area such that one or more LPEC temperature sensors can report temperature measurements according to a particular pattern of target area temperature values. it can. The SPEC temperature sensor can be one or more of a bladder temperature sensor or a rectal temperature sensor.

In another example, the control procedure causes the SPEC to adjust the whole body temperature of the body so that the one or more SPEC temperature sensors exhibit an average temperature in the range of about 32°C to less than about 37°C. The LPEC can be controlled to control the temperature of the blood towards the target region such that the one or more LPEC temperature sensors indicate a temperature of less than about 30°C. The control procedure can cause the SPEC to raise the temperature of the blood so that the average temperature does not drop below about 32°C. The control procedure can cause the LPEC to reduce the temperature of the blood to a value within the range of about 10°C to about 30°C.

Any exemplary system herein can include a control system programmed to perform control procedures. For example, the control system may be programmed to set the flow rate and temperature in the LPEC pump and LPEC heat exchanger independent of the SPEC pump flow rate. The control system may be programmed to cause the LPEC to control the temperature of the blood towards the target area either automatically or based on manual input. The control system may be programmed to cause the SPEC to raise the temperature of the blood so that the average temperature does not drop below about 32°C. The control system may be programmed to cause the LPEC to reduce the temperature of the blood to a value in the range of about 10°C to about 30°C.

Conclusion Although various embodiments of the present invention have been described and shown herein, one of ordinary skill in the art can perform and/or result and/or perform the functions described herein. Various other means and/or structures for achieving one or more of the advantages may be readily envisioned, and each such variation and/or modification is described herein. It is considered to be within the scope of the embodiments of the present invention. More generally, all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and the actual parameters, dimensions, materials, and/or configurations One of ordinary skill in the art will readily appreciate that the teachings of the present invention will vary depending on the particular application for which it is used. One of ordinary skill in the art would be able to use experimentation within routine to recognize or ascertain the many equivalents of the specific embodiments of the invention described herein. Accordingly, the foregoing embodiments are presented by way of example only, and within the scope of the appended claims and their equivalents, the embodiments of the present invention may differ from those specifically described and claimed. It should be understood that this may be done. The embodiments of the invention in this disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. Furthermore, any combination of two or more such features, systems, articles, materials, kits, and/or methods is such that these features, systems, articles, materials, kits, and/or methods are compatible with each other. , Within the scope of the disclosed invention.

The embodiments of the invention described above can be implemented in any of a variety of ways. For example, some embodiments may be implemented using hardware, software, or a combination thereof. When any aspect of the embodiments is implemented at least partially in software, the software code is optional, whether provided on a single computer or distributed among multiple computers. May be performed on any suitable processor or collection of processors.

In this regard, various aspects of the present specification include one or more programs that, when executed on one or more computers or other processors, perform the methods of implementing the various embodiments of the techniques described above. Computer-readable medium (or a plurality of computer-readable mediums) encoded by (for example, computer memory, one or more floppy disks, compact disks, optical disks, magnetic tapes, flash memory, field programmable gate array or others. Circuitry within a semiconductor device, or other tangible computer storage medium or non-transitory medium). A computer-readable medium is removable such that programs stored thereon can be loaded onto one or more different computers or other processors to implement the various aspects of the present technology described above. be able to.

The term "program" or "software" is used herein to refer to any type of computer code or code that may be used to program a computer or other processor to implement the various aspects of the present technology described above. Used in a general sense to refer to computer-executable instructions. Furthermore, according to one aspect of this embodiment, the one or more computer programs that, when executed, perform the method of the present technology need not be on a single computer or processor, but on a number of different computers or processors. It should be understood that the various aspects of the present technology may be distributed in a modular fashion amongst others.

Computer-executable instructions may be in many forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically, the functionality of the program modules may be combined or distributed as desired in various embodiments.

Also, the techniques described herein may be embodied as methods, at least one example of which is provided. The acts performed as part of the method may be ordered in any suitable manner. Thus, embodiments may be constructed in which acts may be performed in a different order than that shown, and the embodiments may show some acts even though they are shown as a series of acts in the exemplary embodiment. May be performed simultaneously.

It is to be understood that all definitions defined and used herein supersede the dictionary definitions, the definitions in the documents incorporated by reference, and/or the usual meanings of the defined terms.

The indefinite articles "a" and "an" as used in the description and the claims are to be understood as meaning "at least one", unless expressly specified otherwise.

The expression "and/or" as used in the description and the claims means "either or both" of the elements connected thereby, ie both conjunctive and disjunctive. It is to be understood as meaning an element that may occur. Multiple elements listed with "and/or" should be construed in the same fashion, ie, "one or more" of the elements connected by it. Other elements may optionally be present, other than those elements specifically identified by the “and/or” clause, whether related or unrelated to those particular elements. Thus, as a non-limiting example, the reference "A and/or B" when used in conjunction with open-ended terms such as "comprising" refers to, for example, only A in one embodiment. (Optionally including elements other than B), and in another embodiment only B (optionally including elements other than A), and in yet another embodiment both A and B Can be referred to (optionally including other elements).

As used in the specification and claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when separating items in a list, "or" or "and/or" should be construed as inclusive, ie, including at least one of a number of elements or a list of elements, At the same time, it should be construed as including two or more of them, and optionally, additional items not listed. The terms "only one of" or "exactly one of" or the like, or "consisting of" when used in the claims, explicitly indicate otherwise. )” is meant to include exactly one of a number of elements or a list of elements. When preceded by an exclusive term such as "any" or "one of", or "only one of", or "exactly one of", Generally, the term "or" as used herein is to be construed only as indicating an alternative (ie, "one or the other but not both"). "Consisting essentially of", when used in the claims, shall have its ordinary meaning as used in the field of patent law.

As used in the specification and claims, the expression "at least one", which refers to a list of one or more elements, refers to at least one element selected from any one or more elements of the list of elements. It is to be understood as meaning an element, but need not necessarily include at least one of each and every element specifically listed in the list of elements, and any combination of elements in the list of elements It's not something to exclude. This definition further determines whether elements other than those specifically identified in the list of elements to which the phrase "at least one" refers are related to or unrelated to those specifically identified elements. Regardless, it is allowed that it may optionally be present. Thus, by way of non-limiting example, for example, "at least one of A and B" (or the same but at least one of A or B), or the same but "A and/or Or “at least one of B”) refers, in one embodiment, to at least one (and optionally to elements other than B) containing two or more A, optionally in the absence of B. In another embodiment, at least one (and optionally other than A) comprising two or more B, optionally in the absence of A, can be referred to, and yet another Embodiments can refer to at least one optionally comprising two or more A's, and optionally at least one comprising two or more B's (and optionally other elements).

In the claims and the above specification, "comprising", "including", "carrying", "having", "containing", "involving". )”, “holding”, “composed of” and the like are understood to be open ended, that is to say including, but not limited to. Should be. Only the transitional phrases “consisting of” and “consisting essentially of” are closed, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures Section 2111.03. Considered a transitional phrase or a semi-closed transitional phrase.

Claims (37)

A system for providing at least two zones of selective temperature therapy, comprising:
An extracorporeal circuit,
An injector member having a distal tip disposed in a vessel position;
A first port for drawing blood from the body,
A second port for returning blood to the body,
A first pump disposed between the first port and the second port for pumping blood from the first port to the second port;
A bifurcating section positioned between the first pump and the second port;
A third port coupled to the bifurcating section and located external to the injector member;
A second pump positioned between the bifurcating section and the third port for controlling a flow rate out of the bifurcating section through the third port and into the injector member. A configured second pump,
A first heat disposed between the first pump and the second port and configured to set the temperature of blood injected into the second port to a first temperature level. An exchange,
To set the temperature of the blood injected into the injector member, which is disposed between the second pump and the injector member, at a second temperature level different from the first temperature level. A system comprising an extracorporeal circuit comprising: a second heat exchanger configured according to. The system of claim 1, further comprising an occlusion component or an additional minimum conductance component disposed proximate the distal tip of the injector member. A controlled flow splitting system,
A first pressure sensor for measuring a first parameter indicative of pressure proximate the distal tip of the injector member;
A second pressure sensor for measuring a second parameter indicative of pressure, the second pressure sensor disposed proximate the injector member at a predefined distance from the distal tip. Further comprising a control flow splitting system comprising
The system of claim 1, wherein the second pump serves as an injection flow source for producing an injection flow in the injector member in a predetermined flow pattern. At least one first temperature sensor positioned to measure an average core body temperature and/or average system temperature of a portion of the body that is perfused using the second port;
The system of claim 1, further comprising at least one second temperature sensor positioned to measure a temperature of a local area perfused by the injector member. An operating console,
A first water cooler/heater for driving the first heat exchanger;
A second water cooler/heater for driving the second heat exchanger;
The system of claim 4, further comprising an operating console with a graphical user interface configured to display user instructions for performing operational steps of the operating sequence. The graphic user interface is
Controlling the temperature of the blood perfused by the second port to adjust the temperature readings reported by the at least one first temperature sensor to stay within a core body target range; The extracorporeal circuit to cause a circuit to perform, and to control the temperature of blood injected into the local region to cause the at least one second temperature sensor to report a temperature measurement within a target region temperature range. 6. The system of claim 5, configured to implement an operating sequence to cause the. The system of claim 1, wherein the first heat exchanger is disposed between the branch section and the first pump. The system of claim 1, wherein the first heat exchanger is disposed between the branch section and the second port. A system for providing at least two zones of selective temperature therapy, comprising:
An extracorporeal circuit,
An injector member having a distal tip disposed in a vascular position,
The first port for drawing blood from the body,
A second port for returning blood to the body,
A first pump disposed between the first port and the second port for pumping blood from the first port to the second port;
A bifurcation section positioned between the first pump and a second port,
A third port coupled to the bifurcating section and located external to the injector member;
A second pump positioned between the bifurcating section and the third port for controlling a flow rate out of the bifurcating section through the third port and into the injector member. A configured second pump,
A first heat disposed between the first pump and the second port and configured to set the temperature of blood injected into the second port to a first temperature level. A second temperature level different from the first temperature level of the temperature of the blood injected into the infuser member disposed between the exchanger and the second pump and the infuser member. An extracorporeal circuit comprising a second heat exchanger configured to set
A controlled flow splitting system proximal to the distal tip, comprising:
A first pressure sensor for measuring a first pressure proximate a distal tip of the at least one injector member, and a proximal pressure disposed from the distal tip for measuring a second pressure A controlled flow splitting system comprising a controlled second pressure sensor,
The system wherein the second pump serves as an injection flow source for producing an injection flow in the injector member in a predetermined flow pattern. A console,
Receiving data indicative of measurements of the first pressure and the second pressure over a time interval T with blood flow infused at the distal tip in the predetermined flow pattern, and the first Of the pressure of the second pressure and the measured flow rate of the second pressure, and using the predetermined flow pattern, the conductance as at least one of a proximal external conductance or a distal external conductance at the distal tip. 10. The system of claim 9, further comprising a console comprising at least one processing unit programmed to perform calculating. The predetermined flow pattern is a first constant flow rate over a _first time interval t ₁ <T and a first constant flow rate over a second time interval t ₂ <T after the first time interval. 11. The system of claim 10, comprising a second constant flow rate different from. The at least one processing unit comprises:
Controlling the flow of the fluid injected at the distal tip over the first time interval t _{1 to} the first constant flow rate, and injecting at the distal tip over the second time interval t _2. 12. The system of claim 11, further programmed to cause the infusion flow source to control the fluid flow to the second constant flow rate. The at least one processing unit comprises:
Recording a first measurement of the first pressure and the second pressure over the first time interval t ₁ using the first pressure sensor and the second pressure sensor; and Further programmed to perform recording second measurements of the first pressure and the second pressure over the second time interval t ₂ using one pressure sensor and the second pressure sensor. 13. The system of claim 12, wherein the system is: The at least one of the proximal outer conductance or the distal outer conductance at the distal tip is the first measurement of the first pressure and the second pressure, the first pressure and the 14. The system of claim 13, calculated using data indicative of the second measurement of a second pressure, the first constant flow rate, and the second constant flow rate. The at least one processing unit predicts at least one of the proximal outer conductance or the distal outer conductance over a third time interval that is later than the first time interval and the second time interval. The system of claim 11, further programmed to calculate. 11. The system of claim 10, wherein the console further comprises a display unit for displaying an indication of at least one of the proximal outer conductance or the distal outer conductance. 10. The system of claim 9, wherein the second pressure sensor is disposed at a distance greater than or approximately equal to twice the diameter of the vasculature. 10. The system of claim 9, wherein the second pressure sensor is disposed proximally from the distal tip a distance greater than about 1.0 cm. A method for establishing and controlling two different temperature zones of at least a portion of the body to perform at least a portion of a treatment procedure for a patient suffering from local or systemic ischemic injury or circulatory injury,
Binding a systemic extracorporeal extracorporeal circuit (SPEC) to the body using a peripherally located loop, the SPEC comprising:
A SPEC input flow port and a SPEC output flow port in contact with blood flowing within the vasculature,
Combining, including a SPEC pump and a SPEC heat exchanger;
Coupling a local extraperfusion fluid circuit (LPEC) to blood flowing within the vasculature towards a local target region of the body, the LPEC comprising:
An LPEC injector member arranged to perfuse the local target area of the body with a distal tip in contact with blood flowing within the vasculature;
At least one of an additional minimum conductance component or controlled flow splitting system disposed proximate the distal tip of the LPEC injector member;
An LPEC pump, and an LPEC heat exchanger, the combining step;
Positioning at least one SPEC sensor for measuring an average core body temperature and/or an average system temperature of the body perfused by the SPEC, and a temperature of the local target area perfused by the LPEC. Positioning at least one LPEC sensor for measuring
Performing at least the operating steps of the minimum operating sequence;
Performing a control procedure for recording measurements of the at least one LPEC sensor and at least one SPEC sensor, and independently controlling blood flow and heat exchanger temperature of each of the SPEC and LPEC. So, the control procedure is
Instructing the SPEC to control the temperature of blood infused by the SPEC to adjust the temperature measurements reported by the SPEC temperature sensor to stay within a target core body temperature range;
Causing the LPEC to control the temperature of blood infused into the target region such that the one or more LPEC temperature sensors report temperature measurements according to a particular pattern of target region temperature values. , Performing a control procedure. An additional minimum conductance component is disposed proximate the distal tip of the LPEC injector member and the additional minimum conductance component directs blood flow within the vasculature to a predetermined minimum flow rate. 20. The method of claim 19, configured to maintain. A controlled flow splitting system is disposed proximate the distal tip of the LPEC injector member, the controlled flow splitting system comprising:
A first pressure sensor for measuring a first pressure proximate a distal tip of the at least one injector member;
A second pressure sensor for measuring a second pressure disposed proximally from the distal tip a distance greater than or approximately equal to twice the diameter of the vasculature. The method according to claim 19. A system for providing assistance,
A local extraperfusion fluid circuit (LPEC) for perfusing a local target area of the body, comprising:
An LPEC input flow port,
LPEC output flow port,
An LPEC input flow port and an output flow port, wherein the LPEC input flow port and the LPEC output flow port are in contact with blood flowing within the vasculature toward the local target area of the body;
An LPEC pump, and an LPEC heat exchanger for controlling the temperature of blood returning to the local target area of the body for the local perfusion,
A controlled flow splitting system disposed proximate the distal tip of the LPEC injector member, the first pressure for measuring a first pressure proximate the distal tip of the LPEC injector member. A sensor and a second pressure sensor disposed proximal to the distal tip of the LPEC injector member for measuring a second pressure,
An LPEC comprising a controlled flow splitting system, wherein the second pump serves as an injection flow source for producing an injection flow in the injector member in a predetermined flow pattern;
A whole-body perfusion fluid circuit (SPEC),
A SPEC input flow port,
A SPEC output flow port,
A SPEC input flow port and a SPEC output flow port, wherein the SPEC input flow port and the SPEC output flow port are in contact with blood flowing within the vasculature in a peripheral portion of the body;
SPEC pump,
One or more SPEC temperature sensors coupled to the body to indicate an average core body temperature and/or an average system temperature of the body perfused by the SPEC;
One or more LPEC temperature sensors coupled to the local target area of the body to indicate temperature within the target area; and a console,
Receiving data indicative of measurements of the first pressure and the second pressure over a time interval T with blood flow infused at the distal tip in the predetermined flow pattern, and the first Of at least one of a proximal external conductance or a distal external conductance at the distal tip of the LPEC injector member using the data indicative of the measured pressure and the second pressure and the predetermined flow pattern. And a SPEC comprising a console comprising at least one processing unit programmed to perform conductance calculations. The predetermined flow pattern is a first constant flow rate over a _first time interval t ₁ <T and a first constant flow rate over a second time interval t ₂ <T after the first time interval. 23. The system of claim 22, comprising a second constant flow rate different from. The at least one processing unit comprises:
Controlling the flow of the fluid injected at the distal tip to the first constant flow rate over the first time interval t ₁ , and the flow of the fluid injected at the distal tip 24. The system of claim 23, further programmed to cause the infusion flow rate source to control the second constant flow rate for a _second time interval t2. The at least one processing unit comprises:
Recording a first measurement of the first pressure and the second pressure over the first time interval t ₁ using the first pressure sensor and the second pressure sensor; and Further programmed to perform recording second measurements of the first pressure and the second pressure over the second time interval t ₂ using one pressure sensor and the second pressure sensor. 25. The system of claim 24, wherein the system is: The at least one of the proximal outer conductance or the distal outer conductance at the distal tip is the first measurement of the first pressure and the second pressure, the first pressure and the 26. The system of claim 25, calculated using data indicative of the second measurement of a second pressure, the first constant flow rate, and the second constant flow rate. The at least one processing unit calculates a prediction of at least one of a proximal outer conductance or a distal outer conductance over a third time interval that is later than the first time interval and the second time interval. 24. The system of claim 23, further programmed to: 23. The system of claim 22, wherein the local target area is the brain. 23. The system of claim 22, wherein the LPEC input flow port is disposed in contact with either the left common carotid artery, the right carotid artery, or an artery downstream of one of these locations. .. 23. The system of claim 22, wherein the systemic perfusion circuit is emergency extracorporeal membrane oxygenation support. 23. The system of claim 22, wherein the one or more SPEC temperature sensors comprises a bladder temperature sensor and/or a rectal temperature sensor. Causing the SPEC to adjust the whole body temperature of the body so that the one or more SPEC temperature sensors exhibit an average temperature within the range of about 32° C. to less than about 37° C.; A control programmed to perform a control procedure comprising causing the LPEC to control the temperature of blood towards the target region such that the LPEC temperature sensor above indicates a temperature of less than about 30°C. Further equipped with a system,
23. The system of claim 22, wherein the control system is programmed to set the flow rate and temperature at the LPEC pump and the LPEC heat exchanger independent of the flow rate at the SPEC pump. 33. The system of claim 32, wherein the control system is programmed to cause the LPEC to control the temperature of blood towards a target area either automatically or based on manual input. 33. The system of claim 32, wherein the control system is further programmed to cause the SPEC to raise the temperature of the blood so that the average temperature does not drop below about 32°C. 33. The system of claim 32, wherein the control system is programmed to cause the LPEC to reduce the temperature of blood to a value in the range of about 10<0>C to about 30<0>C. A system for providing selective temperature therapy, comprising:
i) defining a first lumen distal end, a first lumen proximal end, and a first lumen having a length from the proximal end to the distal end. A first elongate element having a first wall, wherein the first lumen is a delivery lumen for delivering temperature treated blood to a target site in the body. When,
ii) an outlet port located in the first lumen for delivering the temperature treated blood to the target site;
iii) at least one of an additional minimal conductance component or a controlled flow splitting system located in the first lumen, proximal to the outlet port,
iv) A second elongate element having a second wall, wherein a second lumen is defined as the space between the first wall and the second wall, and the second lumen is Is coaxial with the first lumen, the second lumen has a second lumen proximal end and a second lumen distal end, and the second lumen is A supply lumen for receiving normothermic blood from the body, the second lumen being a heat insulating layer along most of the length of the first lumen when receiving the normothermic blood To the first lumen distal end such that the second lumen distal end is in proximity to the first lumen distal end to function as A second elongate element having a second lumen distal end positioned;
v) the second elongate element is insertable into an artery of the body at a peripheral location of the body and is adapted to extend to a remote location of the body;
vi) an inlet located in the second elongate element, the inlet being in proximity to at least one of the additional minimum conductance component or the controlled flow splitting system, for receiving the normothermic blood. ,
vii) a control unit in fluid communication with the proximal ends of the first lumen and the second lumen, the supply blood inlet in fluid communication with the second lumen, A control unit comprising a supply blood inlet for receiving the normothermic blood from the body,
viii) a temperature regulator in fluid communication with the supply blood inlet, the temperature regulator being configured to alter the temperature of the received normothermic blood to provide the temperature treated blood.
ix) a delivery blood outlet in fluid communication with the temperature regulator and in fluid communication with the first lumen for providing the temperature treated blood to the first lumen. And a delivery blood outlet for the system. A device for providing selective temperature therapy, comprising:
i) a first elongate element having a first wall, the space within the first wall defining a delivery lumen;
ii) a second elongated element having a second wall, the second elongated element having a supply lumen defined by a space between the first wall and the second wall; ,
iii) a control unit in fluid communication with the supply lumen and the delivery lumen, and iv) a supply blood inlet in fluid communication with the supply lumen for receiving normothermic blood from the body Supply blood inlet for,
v) a delivery blood outlet in fluid communication with the delivery lumen, the control blood unit comprising a delivery blood outlet for providing temperature treated blood to the delivery lumen.
vi) the supply lumen delivers normothermic blood to the control unit located outside the body,
vii) the delivery lumen receives temperature treated blood from the control unit and supplies the temperature treated blood to a target site in the body, the supply lumen being coaxial with the delivery lumen; The supply lumen is positioned around a majority of the delivery lumen such that the supply lumen acts as an insulating layer along the majority of the delivery lumen when receiving temperature-treated blood. The supply lumen, the control unit and the delivery lumen form a closed system,
viii) said second elongate element is insertable into an artery of said body at a peripheral location of said body and adapted to extend to a remote location of said body,
ix) at a position where at least one of the additional minimum conductance component or controlled flow splitting system is proximal of the distal end of the delivery lumen and distal of the distal end of the supply lumen, A device positioned in the delivery lumen.