Cardiac ex VIVO preservation system compatible for use with any oxygenator and pump

Abstract

Ex vivo preservation systems and methods for preserving a harvested organ for transplantation or reimplantation during an extended preservation and / or treatment period (e.g., over 6 hours). The ex vivo preservation systems disclosed herein are configured to be compatible with any continuous or pulsatile perfusion flow pumps, and any oxygenation systems such as ECMO systems. The disclosed ex vivo preservation systems are also be compact, portable and / or self-contained, allowing relatively easy and convenient movement while transporting a harvested organ to a different geographic location.

Description

CARDIAC EX VIVO PRESERVATION SYSTEM COMPATIBLE FOR USE WITH ANY OXYGENATOR AND PUMP STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0001] None. RELATED APPLICATION DATA

[0002] The present application claims the benefit of priority to U.S. provisional application Serial No. 63 / 575,672, filed April 6, 2024, the entire disclosure of which is expressly incorporated by reference herein. TECHNICAL FIELD

[0003] The present application relates to medical systems and methods and, more particularly, to systems and methods for preservation of harvested (i.e., ex vivo) animal organs (including humans) in a viable condition (e.g., for replantation or transplantation) which is compatible for use with any oxygenator system (e.g., extracorporeal membrane oxygenator (ECMO) systems). BACKGROUND

[0004] Ex vivo preservation is a burgeoning area of research, development, and commercialization, which is rapidly expanding the donor pool for solid organ transplantation such as heart transplants. There are currently two main methods for ex vivo preservation of solid organs, namely, traditional cold storage and more recently, perfusion systems which preserve the organs by maintaining oxygenated blood flow through the organ.

[0005] Cold storage methods of ex vivo organ preservation utilize hypothermic temperature conditions (below 20° C and preferably about 4° C), arrest of organ function, and storage in a chemical perfusate for maintaining the organ and do not endeavor to replicate an in vivo physiologic state for the organ. However, cold storage methods are quite limited in the period of time in which the organ is maintained viable, in most cases not more than 3 to 4 hours. Also, the cold storage and perfusate only partially prevent the organ from being damaged. For instance, a donor heart preserved at hypothermic temperature in a cardioplegic solution still suffers myocardial damage from ischemia and reperfusion, andbeyond the ischemic interval of 3-4 hours, the risk of graft dysfunction increases, leading to significant morbidity and mortality. Hence, although traditional cold storage remains a reliable method, it is limited to donors who live within several hours of the recipient. To extend donor heart ischemic times, preservation techniques such as hypothermic oxygenated perfusion (HOPE) have been introduced, which preserves arrested donor hearts at 8oC while providing continuous oxygenation to minimize ischemic injury (1,2). However, clinical trials of HOPE have been limited to patients weighing over 30 kg.

[0006] In recent years, normothermic ex vivo preservation has also emerged as a highly effective technique, allowing continuous perfusion of the donor’s heart in a beating state to extend transport distances for both donation after circulatory death and donation after brain death donors. For example, in order to increase the time period of viability of organs harvested for transplantation and to minimize damage to the organ during storage and transport, ex vivo preservation systems (EVPS) have been developed which actively perfuse an explanted organ by pumping oxygenated blood through the organ. The ex vivo preservation system may also sustain some level of function of the organ, and / or maintain the organ in normothermic conditions. Due to continuous perfusion of the coronaries, EVPS mediated transports appear better for longer transport time, increasing viability of the organ. For instance, with the ability to actively perfuse an explanted heart, an EVPS machine allows transplantation of donor hearts over longer geographical distances, even for higher- risk donors such as those after circulatory death. To date, the only commercially available ex vivo preservation system in use is the ORGAN CARE SYSTEM™ sold by TransMedics, Inc., which is an all-inclusive technology that can enable heart donations in both DCD (donation after circulatory death) and DBD (donation after brain death) methods. The ORGAN CARE SYSTEM™ is a system which includes a heart containment chamber and connected heart perfusion system, as well as a membrane oxygenator. However, the ORGAN CARE SYSTEM™ machine is limited for use with heart donors that are at least 40kg in size, and is not approved for use on donor patients in the pediatric population, and therefore the benefits of EVPS in organ transplantation remain out of reach for this vulnerable population. In addition, the ORGAN CARE SYSTEM™ machine is bulky, comprises numerous and lengthy cord and tube connections and a heavy heating / cooling unit. The ORGAN CARE SYSTEM™ machine also presents a risk of thrombosis caused by air bubbles and characteristics of the perfusion fluid circulated through the heart, and also has a limited function period because the system is very large and utilizes a large amount ofpower for the heater and pump. But again, such ex vivo systems are only for use with donors weighing above 40 kg.

[0007] Thus, there remains a critical clinical gap in donor heart preservation for low-weight patients. These challenges lead to the underutilization of pediatric donor hearts and pose a higher risk to patients on the waiting list. Therefore, there is an urgent need for an efficient and highly accessible normothermic ex vivo preservation system to treat pediatric patients who are on the waiting list with critical conditions. Accordingly, an ex vivo preservation system for harvested organs compatible for use with organ donors of any size or age, including pediatric hearts, and which is configured for use with any of the blood oxygenation systems (e.g., ECMOs) with which most hospitals are equipped, would be useful and beneficial. The system should be compact, lightweight, utilize and minimize the number and length of tubing connections, and provide continuous monitoring of organ and system parameters and cords. SUMMARY

[0008] The present application is directed to medical devices and, more particularly to ex vivo preservation systems and methods for preserving a harvested organ for transplantation or reimplantation during an extended preservation and / or treatment period (e.g., over 6 hours) during which the harvested organ may be transported to a different geographic location and / or maintained until the recipient is ready for the organ to be transplanted or reimplanted. The ex vivo preservation systems disclosed herein are configured to be compatible with any continuous or pulsatile perfusion flow pumps, and any oxygenation systems such as ECMO systems. The disclosed ex vivo preservation systems may also be compact, portable and / or self-contained, allowing relatively easy and convenient movement while transporting a harvested organ to a different geographic location.

[0009] Accordingly, in a first embodiment disclosed herein is directed to an ex vivo organ preservation system (EVPS) configured for connection to an oxygenation system with integrated perfusion fluid pumping functionality. For instance, the oxygenation system may be a typical ECMO system available at most hospitals. The EVPS is configured to perfuse and maintain an explanted organ over an extended period of time, for example, for over 6 hours if needed to transport the organ and prepare the recipient for implantation. Although the organ may be any suitable animal or human organ, many of the embodiments disclosedherein are directed to preserving donor hearts and more specifically, pediatric donor hearts, as there is a vital need in this vulnerable population. Hence, certain embodiments disclosed herein may be described with respect to generic organs, while other embodiments may be disclosed with respect to hearts or pediatric hearts, with the understanding that each may be used with any suitable donor organ.

[0010] This first embodiment of an EVPS comprises an organ chamber assembly for containing a harvested organ (i.e., ex vivo organ). The organ chamber assembly includes an organ container having a base, a wall portion extending upward from the base to an open top of the middle portion, and a top lid configured to fit onto the open top of the middle portion thereby enclosing the organ container. The organ container may have any suitable shape, such as a cylindrical container in which the middle portion comprises a cylindrical tube, a rectangular container in which the middle portion comprises a four-sided box, or other shape in which the middle portion has a cross-section in the shape of an oval, square, polygon, etc.

[0011] The top lid comprises most of the fluid connections and may also include openings for cords and devices to access the interior of the organ container. In this embodiment, the top lid has a perfusion fluid inlet port, a vent port, and a defoamer port. The perfusion fluid inlet port has an external inlet port connector configured to be connected to an outlet line from an oxygenation system and an internal organ perfusion connector configured to be connected to an organ in the organ chamber. The term “external” refers to an element being on the outer side of the top lid which is outside of the organ container when the top lid is installed on the open top of the middle portion, and the term “internal” refers to an element being on the inner of the top lid which is inside of the organ container organ when the top lid is installed on the open top of the middle portion. The outlet line of the oxygenation system conveys oxygenated perfusion fluid from the oxygenation system. The vent port has an external vent outlet connector configured to be connected to an inlet of a vent pump and an internal vent connector configured to be connected to an outlet of a vent tube. The vent tube is a tube for circulating the perfusion fluid after it has passed through the organ (i.e., perfused the organ) back into a perfusion fluid reservoir within the organ container. The defoamer port has an external defoamer connector configured to be connected to an outlet of the vent pump and an internal defoamer connector configured to be connected to a defoamer positioned within the organ container. The vent pump is a fluid pump that pumps the perfusion fluid through the venttube and through the vent port, then through the defoamer port and the defoamer into fluid reservoir in the organ container.

[0012] The EVPS further comprises a perfusion fluid outlet port disposed at or near the bottom of the organ container. For example, the perfusion fluid outlet port may be in the bottom of the wall portion or in the base of the organ container. The perfusion fluid outlet port has an internal opening in fluid communication with an inside of the organ container and an external outlet port connector configured to be connected to an inlet line to the oxygenation system. As the perfusion fluid outlet port is connected in fluid communication with the inlet line of the oxygenation system, the organ container is also a perfusion fluid reservoir which supplies the oxygenation system with perfusion fluid.

[0013] The EVPS also includes a vent pump, as mentioned above. The vent pump has a vent pump inlet connected in fluid communication with the external vent outlet connector of the top lid and a vent pump outlet connected in fluid communication with the defoamer port (e.g., a tube extending from the vent pump outlet and connected to the external defoamer connector). As described above, the vent pump is configured to pump perfusion fluid in through the vent tube and out through the defoamer port into the defoamer and into the perfusion fluid reservoir within the organ container.

[0014] The EVPS also comprises a perfusion fluid level sensor positioned within the organ container. The perfusion fluid level sensor is configured to detect a level of the perfusion fluid within the organ container and to provide a fluid level signal corresponding to the detected level of perfusion fluid. When the perfusion fluid level drops below a set minimum level, the EVPS may trigger a low perfusion fluid level warning indicating to add perfusion fluid into the perfusion fluid reservoir within the organ container.

[0015] The first embodiment of an EVPS may include any combination of one or more of the following additional aspects, features, components, and / or functionalities. None of these additional aspects, features, components, and / or functionalities is considered essential unless inclusion is explicitly or inherently required by another aspects, features, components, and / or functionalities.

[0016] In another aspect of the first embodiment, the EVPS may further include the defoamer positioned within the organ container. The defoamer is operably connected to the internal defoamer connector, and the defoamer is configured to reduce foam in the perfusion fluid as it flows out of the defoamer and into the perfusion fluid reservoir within the organ container.

[0017] In still another aspect, the EVPS may also include a hemoconcentrator connected between the perfusion fluid outlet port and the perfusion fluid inlet port. The hemoconcentrator is configured to selectively remove certain components, such as water, electrolytes and low-molecular weight substances, from the perfusion fluid circulating through the ex vivo organ preservation system.

[0018] In yet another feature, the EVPS may further comprise a defibrillator for shocking an organ, such as a heart, to re-start or alter function of the organ, for example, after function of the organ has been arrested or modified. The defibrillator has defibrillator contacts (e.g., electrodes, paddles, or the like) for insertion inside the organ container for placement in contact with the organ and is configured to deliver a controlled electric shock to the organ. In yet another aspect, the top lid may include one or more defibrillator openings for providing access for the defibrillator contacts to be inserted inside the organ container. The top lid may also have one or more adjustable covers configured to open and close the defibrillator openings. For example, the adjustable covers may be sliding windows which can slide open and closed.

[0019] In another aspect, the EVPS may also include a pacemaker configured to regulate a function of an organ being preserved in the organ container of the ex vivo organ preservation system. The pacemaker is especially useful for preserving a heart in the EVPS. In order to accommodate the pacemaker, the top lid may include a pacemaker port for providing access for the pacemaker electrodes and lead wires into the organ container.

[0020] In another aspect, the EVPS may further include a heart rate sensor configured to detect a heart rate of a harvested organ being preserved in the ex vivo organ preservation system and provide a heart rate signal corresponding to the detected heart rate. The heart rate sensor may include a probe for attachment to the heart to detect the heart rate. In another aspect, the heart rate sensor may be operably coupled to the pacemaker and the pacemaker may be configured to use the heart rate signal to regulate the function of the heart. In another aspect, the heart rate sensor may be integrated with the pacemaker.

[0021] In yet another aspect, the EVPS may further comprise a compact heating / cooling unit for controlling the temperature of the perfusion fluid. The heating / cooling unit is configured to heat and cool the perfusion fluid, and in another aspect, to maintain the perfusion fluid at a normothermic temperature (37° C ± 4° C). In another feature, the EVPS may also have a temperature sensor positioned within the organ container. The temperature sensor is configured to detect a temperature of the perfusionfluid within the organ container and provide a temperature signal corresponding to the detected temperature of the perfusion fluid. The heating / cooling unit and temperature sensor may be operably coupled to a controller which is configured to control the heating / cooling unit to control the temperature of the perfusion fluid based on the temperature signal. For instance, the controller may utilize a closed loop control algorithm to control the heating / cooling unit based on the temperature signal.

[0022] In still another aspect, the heating / cooling unit may comprise a Peltier module and electric coils. In still additional aspect, the heating / cooling unit may be lightweight and compact, such as having a maximum weight of 3 kg, and occupying a volume of less than 1000 sq. cm. In yet another aspect, the heating / cooling unit may be is battery-powered. This allows the EVPS to be portable and fully self-contained (i.e., operable without connection to any external power source). In yet another aspect, the heating / cooling unit may comprise a heating / cooling pad configured to be placed in contact with a component of one of the ex vivo organ preservation system and the oxygenation system to heat and cool the perfusion fluid.

[0023] In another aspect, the EVPS may also include a blood gas monitor configured to sample the perfusion fluid and determine blood gas parameters of the perfusion fluid. The blood gas monitor may determine blood gas parameters such as partial pressure (pressure of oxygen dissolved oxygen in blood), oxygen saturation (percentage of hemoglobin bound to oxygen), total oxygen content (dissolved + bound to hemoglobin), partial carbon dioxide, pH (blood acidity or alkalinity), bicarbonate, lactate, electrolytes (e.g., sodium, potassium, chlorine, calcium), etc.

[0024] In still a further aspect, the EVPS may also include a plurality of organ platforms (also referred to as “bridges”) each configured to be individually positioned within the organ container to support an organ placed onto the organ platform. This allows the organ container to accommodate any size organ from any age and size donor, including pediatric organs (e.g., pediatric hearts). Each organ platform has a different height to accommodate within the organ container different size organs from donors of any age or size. The use of the organ platforms is straightforward. The organ platform having the correct height to position the organ in the organ container so that the organ fits within the organ container with the top lid secured and also positions the organ for convenient connection to the internal organ perfusion connector is selected and placed in the organ container. The organ platform may sit on the inside of the base. The harvested organ is thenplaced on the platform within the organ container. In another aspect, the organ platforms may have holes through the surface of the platform to allow perfusion fluid to flow through the platforms and into the fluid reservoir within the organ container.

[0025] In another aspect, the EVPS may be specifically configured to preserve a pediatric heart from a donor weighing less than 40 kg. In this case, the organ container may have a diameter of from 10 cm to 14 cm and a height of from 10 cm to 15 cm, to accommodate a pediatric heart.

[0026] In yet another aspect, the EVPS may further comprise a data acquisition system operably coupled to one or more of the fluid level sensor, temperature sensor, blood gas monitor heart rate sensor, pacemaker, and / or oxygenation system. The data acquisition system is configured to continuously monitor and store operational and / or organ data (collectively, “system data parameters”) over time during use of the ex vivo organ preservation system. The system data parameters may including the heart rate, perfusion fluid temperature, blood gas parameters, perfusion fluid pressure, perfusion flow rates through the oxygenation system and / or vent pump, etc.

[0027] A second embodiment disclosed herein is directed to a method of using the first embodiment of an EVPS disclosed herein, which may include any combination of one or more of the additional aspects, features, components, and / or functionalities disclosed herein, to preserve an explanted organ for up to a period of six hours or more. Accordingly, a method of using the disclosed EVPS includes, within a surgical setting (e.g., a surgical room within a hospital, or any other location at which an organ is being explanted from a donor patient), connecting the ex vivo organ preservation system to an oxygenation system. As described herein, the EVPS is configured to be used with any oxygenation system, such as an ECMO. The EVPS is connected to the oxygenation system by the following process. The perfusion fluid outlet port of the EVPS is connected to an inlet line in fluid communication with a perfusion fluid inlet of the oxygenation system. This fluidly connects the perfusion fluid reservoir within the organ container to the fluid inlet of the oxygenation system. The external inlet port connector of the EVPS is connected to an outlet line in fluid communication with a perfusion fluid outlet of the oxygenation system. This connects the outlet of the oxygenation system which outputs oxygenated perfusion fluid. The oxygenation system is configured to receive perfusion fluid via the perfusion fluid inlet, oxygenate the perfusion fluid, and output the oxygenated perfusion fluid out through the perfusion fluid outlet. For example, in the case that the oxygenation system is an ECMO,the ECMO uses a membrane oxygenation process to oxygenate the perfusion fluid and remove carbon dioxide.

[0028] The method further includes explanting an organ from an organ donor. The explanting process includes surgically accessing the organ to be harvested. Then, a first end of a graft is sutured to a blood vessel of the organ and a second end of the graft is secured to the internal organ perfusion connector of the top lid of the organ container. The vent tube is positioned into the organ such that the inlet of the vent tube is positioned at a venting location at which perfusion fluid is intended to flow through the organ and connecting the outlet of the vent tube to the internal vent connector of the top lid. The organ is surgically removed from the organ donor and placed into the organ container. The organ may be fully surgically removed before, after, or during the other steps of the process of explanting the organ and connecting the organ to the EVPS. The top lid is then secured onto the open top of the middle portion of the organ container.

[0029] The EVPS and oxygenation system may be primed by filling the organ container, vent pump, oxygenation system and / or fluid lines with perfusion fluid. Typically, the perfusion fluid includes blood collected from the donor, in addition to nutrients and medications given as part of the preservation protocol.

[0030] The EVPS and oxygenation system are then operated to perform the preservation process, as follows. The oxygenation system pumps perfusion fluid from the fluid reservoir of the organ container out through the perfusion fluid outlet port and into the oxygenation system. The oxygenation system oxygenates the perfusion fluid and pumps the oxygenated perfusion fluid out through the perfusion fluid outlet of the oxygenation system.

[0031] The oxygenated perfusion fluid from the perfusion fluid outlet flows through the perfusion fluid inlet port of the top lid of the organ container, through the graft into the blood vessel of the organ. The perfusion fluid flows through blood vessel branches of the organ to the venting location of the organ. The vent pump pumps the perfusion fluid from the venting location through the vent tube and through the vent port, then out through the defoamer port and into the fluid reservoir in the organ container. If the EVPS includes a defoamer, the perfusion fluid flows through the defoamer and is defoamed before it flows into the fluid reservoir.

[0032] Accordingly, the method of using the EVPS connected to an oxygenation system to preserve an explanted organ can maintain the explanted organ for an extended period of time. The method of using the EVPS to preserve an explanted organ may alsoinclude a combination of one or more additional steps, processes and functions. For example, in the case that the EVPS includes a pacemaker and a heart rate sensor, the pacemaker may regulate a function of the organ. For example, in the case of an explanted heart, the pacemaker regulates the function of the heart, including, for example, the heart rate.

[0033] In the case that the EVPS includes a heating / cooling unit and a temperature sensor, the method further includes the heating / cooling unit heats and / or cools the perfusion fluid to control the temperature of the perfusion fluid. For example, the EVPS and oxygenation system can perform a normothermic preservation of the organ which maintains the perfusion fluid and organ substantially at its normal in vivo temperature. In the case of temperature, the term “substantially” means within ± 10%.

[0034] In the case that the EVPS comprises a blood gas monitor, the method may further comprise the blood gas monitor sampling the perfusion fluid and determining blood gas parameters of the perfusion fluid, including one or more of partial pressure (pressure of oxygen dissolved oxygen in blood), oxygen saturation (percentage of hemoglobin bound to oxygen), total oxygen content (dissolved + bound to hemoglobin), partial carbon dioxide, pH (blood acidity or alkalinity), bicarbonate, lactate, and / or electrolytes (e.g., sodium, potassium, chlorine, calcium).

[0035] In the case that the EVPS includes a plurality of organ platforms, the method may further include selecting one of the organ platforms having the correct height to position the organ in the organ container so that the organ fits within the organ container with the top lid secured and also positions the organ for convenient connection to the internal organ perfusion connector. The organ is then placed on the selected organ platform in the organ container, for example, after the organ is secured to the internal organ perfusion connector using the graft and and / or the vent tube has been positioned into the organ.

[0036] In the case that the EVPS is specifically configured to preserve a pediatric heart from a donor weighing less than 40 kg, the organ container has a diameter of from 10 cm to 14 cm and a height of from 10 cm to 15 cm.

[0037] In the case that the EVPS further comprises a data acquisition system operably coupled to one or more of the fluid level sensor, temperature sensor, blood gas monitor heart rate sensor, pacemaker, and / or oxygenation system, the data acquisition system continuously monitors and stores one or more of the system data parameters over time during preservation of the organ using the EVPS.

[0038] A third embodiment disclosed herein is directed to an ex vivo heart preservation system (also referred to as a “heart EVPS”) for connection to an oxygenation system to form a heart perfusion system for preserving a harvested heart. The heart EVPS is substantially the same as the first embodiment of EVPS described above, except that the heart EVPS is specifically configured to preserve an explanted heart. Accordingly, the heart EVPS includes a heart chamber assembly for containing an ex vivo heart. The heart chamber assembly includes a heart container having a base, a wall portion extending upward from the base to an open top of the middle portion, and a top lid configured to fit onto the open top of the middle portion. The top lid has a perfusion fluid inlet port, a left ventricle (LV) vent port, and a defoamer port. The perfusion fluid inlet port has an external inlet port connector configured to be connected to an outlet line from an oxygenation system and an internal aorta connector configured to be connected to an aorta of a harvested heart placed in the organ chamber. The LV vent port has an external vent outlet connector configured to be connected to an inlet of a vent pump and an internal vent connector configured to be connected to an outlet of an LV vent tube. The LV vent tube is configured to be inserted into the left ventricle of the harvested heart. The defoamer port has an external defoamer connector configured to be connected to an outlet of the vent pump and an internal defoamer connector configured to be connected to a defoamer positioned within the organ container;

[0039] The heart EVPS also includes a perfusion fluid outlet port, vent pump, and perfusion fluid level sensor, same as such components of the first embodiment of an EVPS, as described herein.

[0040] The heart EVPS also include a pacemaker configured to regulate a function of a heart being preserved in the heart container. In order to accommodate the pacemaker, the top lid may include a pacemaker port for providing access for the pacemaker electrodes and lead wires into the organ container. The heart EVPS also comprises a heart rate sensor configured to detect a heart rate of the harvested heart being preserved in the heart EVPS and provide a heart rate signal corresponding to the detected heart rate. The heart rate sensor includes a probe for attachment to the heart to detect the heart rate. In another aspect, the heart rate sensor may be operably coupled to the pacemaker and the pacemaker may be configured to use the heart rate signal to regulate the function of the heart. In an alternative aspect, the heart rate sensor may be integrated with the pacemaker.

[0041] The heart EVPS may also include any combination of one or more of theadditional aspects, features, components, and / or functionalities described above with respect to the first embodiment of an EVPS, above, wherein the organ in such descriptions refers to a “heart.” Again, none of these additional aspects, features, components, and / or functionalities is considered essential unless inclusion is explicitly or inherently required by another aspects, features, components, and / or functionalities.

[0042] A fourth embodiment disclosed herein is directed to a method of using the heart EVPS, which may include any combination of one or more of the additional aspects, features, components, and / or functionalities disclosed herein, to preserve an explanted heart for up to a period of six hours or more. Accordingly, a method of using the disclosed heart EVPS includes, within a surgical setting (e.g., a surgical room within a hospital, or any other location at which an organ is being explanted from a donor patient), connecting the heart EVPS to an oxygenation system. As described herein, the heart EVPS is configured to be used with any oxygenation system, such as an ECMO. The heart EVPS is connected to the oxygenation system by the following process. The perfusion fluid outlet port of the heart EVPS is connected to an inlet line in fluid communication with a perfusion fluid inlet of the oxygenation system. This fluidly connects the perfusion fluid reservoir within the heart container to the fluid inlet of the oxygenation system. The external inlet port connector of the EVPS is connected to an outlet line in fluid communication with a perfusion fluid outlet of the oxygenation system. This connects the outlet of the oxygenation system which outputs oxygenated perfusion fluid. The oxygenation system is configured to receive perfusion fluid via the perfusion fluid inlet, oxygenate the perfusion fluid, and output the oxygenated perfusion fluid out through the perfusion fluid outlet. For example, in the case that the oxygenation system is an ECMO, the ECMO uses a membrane oxygenation process to oxygenate the perfusion fluid and remove carbon dioxide.

[0043] The method further includes explanting a heart from a heart donor. The explanting process includes surgically accessing the heart to be harvested, such as by performing a sternotomy. Then, a first end of a graft is sutured to the aorta of the heart and a second end of the graft is secured to the internal aorta connector of the top lid of the heart container. The LV vent tube is positioned into the heart such that the inlet of the LV vent tube is positioned in the left ventricle and connecting the outlet of the LV vent tube to the internal vent connector of the top lid. The heart is surgically removed from the heart donor and placed into the heart container. The heart may be fully surgically removed before, after, or during the other steps of the process of explanting the heart and connecting the heart tothe heart EVPS. The top lid is then secured onto the open top of the middle portion of the heart container.

[0044] Then, the heart EVPS and oxygenation system are primed by filling the heart container, vent pump, oxygenation system and / or fluid lines with perfusion fluid.

[0045] The heart EVPS and oxygenation system are then operated to perform the heart preservation process, as follows. The oxygenation system pumps perfusion fluid from the fluid reservoir of the heart container out through the perfusion fluid outlet port and into the oxygenation system. The oxygenation system oxygenates the perfusion fluid and pumps the oxygenated perfusion fluid out through the perfusion fluid outlet of the oxygenation system.

[0046] The oxygenated perfusion fluid from the perfusion fluid outlet flows through the perfusion fluid inlet port of the top lid of the heart container, through the graft into the aorta of the heart. The perfusion flow through the heart is retrograde, i.e., in the opposite flow direction to blood flow through the heart when the heart is pumping blood in a human. The aorta valve is closed due to the retrograde flow, so the perfusion fluid flows through the myocardium of the heart to the left ventricle and right ventricle of the heart. The perfusion fluid flows from the right ventricle out through the pulmonary artery of the heart and into the fluid reservoir in the heart container. The vent pump pumps the perfusion fluid from the left ventricle through the vent tube and through the vent port, then out through the defoamer port and into the fluid reservoir in the heart container. If the heart EVPS includes a defoamer, the perfusion fluid flows through the defoamer and is defoamed before it flows into the fluid reservoir.

[0047] Accordingly, the method of using the EVPS connected to an oxygenation system to preserve an explanted heart can maintain the explanted heart for an extended period of time while the heart can be transported to the recipient patient and the recipient can be prepped for implantation. The method of using the heart EVPS to preserve an explanted heart may also include a combination of one or more additional steps, processes and functions, as described herein for the second embodiment directed to a method of using the first embodiment of an EVPS.

[0001] Other aspects and features of the embodiments disclosed herein invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0048] It is believed the present invention will be better understood from the following description of certain examples taken in conjunction with the accompanying drawings, in which like reference numerals identify the same elements and in which:

[0049] FIG. 1 is a block diagram of an ex vivo preservation system for an explanted heart connected to an oxygenation system, according to one embodiment disclosed herein.

[0050] FIG. 2 is a schematic diagram of the ex vivo preservation system for an explanted heart and oxygenation system of Fig. 1.

[0051] FIG. 3 is a block diagram showing the schematically showing the separate ex vivo preservation system apart from the oxygenation system.

[0052] FIG. 4 illustrates the heart chamber assembly of the ex vivo preservation system for an explanted heart and oxygenation system of Fig. 1, according to one embodiment disclosed herein.

[0053] FIGS. 5A-5B illustrate the top lid of the heart chamber assembly of FIG. 4, according to one embodiment disclosed herein.

[0054] FIG. 6 illustrates a plurality of platforms for individual placement within the heart chamber assembly of FIG. 4 to accommodate different size hearts in the ex vivo preservation system.

[0055] The drawings are not intended to be limiting in any way, and it is contemplated that various examples of the invention may be carried out in a variety of other ways, including those not necessarily depicted in the drawings. The accompanying drawings incorporated in and forming a part of the specification illustrate several aspects of the present invention, and together with the description serve to explain the principles of the invention; it being understood, however, that this invention is not limited to the precise arrangements shown. DETAILED DESCRIPTION

[0056] The following description of certain examples of the invention should not be used to limit the scope of the present invention. Other examples, features, aspects, embodiments, and advantages of the invention will become apparent to those skilled in the art from the following description, which is by way of illustration, one of the best modes contemplated for carrying out the invention. As will be realized, the invention is capable of other different and obvious aspects, all without departing from the invention. Accordingly,the drawings and descriptions should be regarded as illustrative in nature and not restrictive.

[0057] Before the examples are described, it is to be understood that the invention is not limited to particular examples described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular examples only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[0058] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0059] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials are now described.

[0060] It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” includes a plurality of such compounds and reference to “the polymer” includes reference to one or more polymers and equivalents thereof known to those skilled in the art, and so forth.

[0061] Certain ranges are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

[0062] Referring to the drawings, FIGS. 1-3 illustrate one embodiment of a harvested organ system 10 comprising an ex vivo preservation system 100 (EVPS 100) for preserving an organ connected to an oxygenation system 200. The embodiment shown in FIGS. 1-3 shows a harvested organ system 10 and EVPS 100 for preserving a heart (also referred to as a “heart EVPS”), but is should be understood that the harvest organ system 10 and EVPS 100 may be used to preserve any suitable organ, which may require minor modifications to the components and the methods of use, which are described herein.

[0063] Turning first to the heart EVPS 100, the EVPS 100 includes a heart chamber assembly 102 for containing the harvested heart 101. As shown in FIGS. 2 and 4-5, the heart chamber assembly 102 which includes a heart container 104 having a base 106, a wall portion 108 extending upward from the base 106 to an open top 110 of the middle portion 108, and a top lid 112 configured to fit onto the open top 110 of the middle portion 108. The heart container 104 illustrated in the figures has in which the middle portion has a cylindrical shape, i.e., a circular cross-section. Nevertheless, the heart container 104 may have any suitable shape, such as a cylindrical container, a rectangular container in which the middle portion comprises a four-sided box, or other shape in which the middle portion has a cross-section in the shape of an oval, square, polygon, etc.

[0064] The top lid 112 comprises a plurality of fluid connections and openings for cords, tubes and sensors to access the interior of the heart container 104. The top lid 112 has a perfusion fluid inlet port 114, a left ventricle (LV) vent port 116, and a defoamer port 118. The perfusion fluid inlet port 114 has an external inlet port connector 120 configured to be connected to an outlet line 122 (also referred to as an arterial line 122) from the oxygenation system 200 and an internal aorta connector 124 configured to be connected to the aorta 126 (see FIGS. 1-3) of the harvested heart 101 positioned within the heart container 104. The LV vent port 116 has an external vent outlet connector 128 configured to be connected to the inlet 130 of a vent pump 132 and an internal vent connector 134 configured to be connected to an outlet of an LV vent tube 136. The LV vent tube 136 is configured to be inserted into the left ventricle 138 of the harvested heart 101. The defoamer port 118 has an external defoamer connector 140 configured to be connected to the outlet 142 of the vent pump 132 and an internal defoamer connector 144 connected to a defoamer 146 positioned within the heart container 104.

[0065] As shown in FIGS. 4, 5A and 5B, the top lid 112 may also have one or more defibrillator openings 148 for providing access for defibrillator contacts to be inserted insidethe heart container 104 through the top lid 112. The illustrated embodiment of FIGS. 4, 5A and 5B includes two defibrillator openings 148. The top lid also has an adjustable cover 149, such as a sliding window, for each defibrillator opening 148 configured to open and close the defibrillator openings 148.

[0066] The heart EVPS 100 may be specifically configured to preserve a pediatric heart 101 from a donor weighing less than 40 kg. In such an embodiment, the heart container 104 may have a diameter of from 10 cm to 14 cm and a height of from 10 cm to 15 cm, to accommodate a pediatric heart 101.

[0067] In order to effectively accommodate donor hearts of various sizes, the heart EVPS 100 also includes a plurality of heart platforms 180a-180d (also referred to as “bridges”), as shown in FIG. 6. The heart platforms 180 are each configured to be individually positioned within the heart container 104 to support the heart 101 placed onto the heart platform 180. Each heart platform 180 has a different height to accommodate within the heart container 104 different size hearts 101 from donors of any age or size. The heart platform 180a has the smallest height for use with relatively larger hearts 101, while the heart platform 180d has the largest height for use with relatively smaller hearts 101. Each of the organ platforms 180 has holes through the surface of the platform 180 to allow perfusion fluid to flow through the platforms 180 and into the fluid reservoir 156 within the heart container 104.

[0068] The heart container 104 and heart platforms 180 are designed such that the heart 101 remains upright within the heart container 104 with the aorta at the top of heart 101 so that it can conveniently be connected to the internal aorta connector 124 via the graft 125. The heart platform 180 having the correct height to position the heart 101 in the heart container 104 so that the heart fits within the heart container 104 with the top lid 112 secured and also positions the heart for convenient connection to the internal aorta connector 124 is selected and placed in the heart container 104. The organ platform 180 may sit on the inside of the base 106. The harvested heart is then placed on the platform 180 within the heart container 104.

[0069] Still referring to FIG. 4, heart chamber assembly 102 has a perfusion fluid outlet port 150 disposed at or near the bottom of the heart chamber assembly 102, such as the bottom of the base 106 and / or heart container 104. In the illustrated embodiment of FIG. 4, the perfusion fluid outlet port 150 is at the bottom of the base 106 of the heart container 104. The perfusion fluid outlet port 150 has an internal opening in fluid communicationwith the inside of the heart container and an external outlet port connector 152. The external outlet port connector is configured to be connected to an inlet line 154 (also referred to as a “venous line 154) to the oxygenation system 200. As shown in FIGS. 1-4, the interior volume of the heart container 104 is a perfusion fluid reservoir 156 which is partially filled with perfusion fluid to supply the oxygenation system 200 with perfusion fluid to be oxygenated.

[0070] The heart EVPS 100 also includes a vent pump 132. The vent pump 132 may be any suitable fluid pump for pumping blood perfusion fluid without damaging the blood cells, such as a peristaltic pump, roller pump, or the like. The vent pump inlet 130 is connected in fluid communication with the external vent outlet connector 128 of the top lid 112 and the vent pump outlet 142 is connected in fluid communication with the defoamer port 118. As shown in FIG. 2, these fluid connections may be formed by a tube 158 extending from the external vent outlet connector 128 to the external defoamer connector 140, or by any one or more tubes forming similar fluid connections. As described herein, the vent pump 132 pumps perfusion fluid in through the LV vent tube 136 and out through the defoamer port 118 into the defoamer 146 and into the perfusion fluid reservoir 156 within the heart container 104. The defoamer 146 is fluidly connected to the internal defoamer connector 144. The defoamer 146 is a device which reduces foam in the perfusion fluid and outputs the defoamed perfusion fluid into the perfusion fluid reservoir 156 within the heart container 104.

[0071] The heart EVPS 100 also comprises a pacing system 160, several perfusion fluid conditioning devices, a number of sensors and detection device, and a data acquisition and control system 162, for controlling, monitoring and recording the operation of the system 10. The pacing system 160 includes a defibrillator 164 and a pacemaker 166. The defibrillator 164 is used to shock the heart 101 to re-start or alter the function of the heart. For example, if the heart is arrested for harvesting the heart from the heart donor, the defibrillator 164 is used to shock the heart 101 to re-start the heart beating. The defibrillator 164 has defibrillator contacts 168 (see Fig. 2) inserted inside the heart container 104 through the defibrillator openings 148 in the top lid 112 and placed in contact with the heart 101 to deliver a controlled electric shock to the heart 101.

[0072] The pacemaker 166 is connected to the heart 101 using a pacemaker leads 167 attached to the heart 101. The pacemaker 166 regulates the beating rhythm and function of the heart 101 while it is being preserved in the heart EVPS 100. The top lid 112has one or more accessory ports or openings for providing access for the lead wires and other devices into the heart container 104. A heart rate sensor 170 is also provided in the heart container 104 which detects a heart rate of the harvested heart 101 being preserved in the heart EVPS 100. The heart rate sensor 170 provides a heart rate signal corresponding to the detected heart rate. The heart rate sensor 170 includes a probe 172 for attachment to the heart 101 to detect the heart rate. The heart rate sensor 170 is operably coupled to the data acquisition and control system 162. The heart rate sensor 170 may also be operably coupled to the pacemaker 166 and the pacemaker 166 may be configured to use the heart rate signal to regulate the function of the heart 101. In an alternative embodiment, the heart rate sensor 170 may be integrated with the pacemaker 166.

[0073] The heart EVPS 100 also has a perfusion fluid level sensor 174 positioned within the heart container 104. The perfusion fluid level sensor 174 detects the level of the perfusion fluid in the perfusion fluid reservoir 156 within the heart container 104 and provide a perfusion fluid level signal corresponding to the detected level of perfusion fluid. The perfusion fluid level sensor 174 is operably coupled to the data acquisition and control system 162. A fluid level sensor circuitry 175 operably coupled to the fluid level sensor 174 may also be provided to condition and / or generate the fluid level signal using the fluid level sensor 174. The data acquisition and control system 162 is configured to monitor the perfusion fluid level in the fluid reservoir 156 using the perfusion fluid level signal, and is configured to provide a low perfusion fluid level warning indicating to add perfusion fluid into the system 10 when the perfusion fluid level drops below a set minimum level. It is important to maintain a minimum level of perfusion fluid in the perfusion fluid reservoir 156 in order to prevent air bubble formation and entrapment in the harvested organ system 10 in order to mitigate the risk of embolism or clot formation in the heart 101.

[0074] The heart EVPS 100 includes one or more pressure sensors 188 and flow sensors 190 to detect and monitor the perfusion fluid pressure and flow rates in the perfusion fluid circuit of the heart EVPS 100. A first pressure sensor 188a is positioned on the inlet line 154 to the oxygenation system 200 and measures the perfusion fluid pressure upstream of the oxygenation system 200 (e.g., the pre-membrane pressure of an ECMO). A second pressure sensor 188b is position on the outlet line 122 downstream of the oxygenation system 200. A first flow sensor 190a is positioned on the outlet line of 154 of the oxygenation system 200 to measure the flow rate of perfusion fluid out of the oxygenation system 200 and into the aorta 126 of the heart 101. A second flow sensor 188bis positioned on the tube to the vent pump 132 to measure the flow rate of perfusion fluid through the LV vent tube 136. The pressure sensor 188 and flow sensors 190 are operably coupled to the data acquisition and control system 162.

[0075] The heart EVPS 100 also has a compact heating / cooling unit 178 for controlling the temperature of the perfusion fluid circulating through the harvested organ system 10. Maintaining the perfusate blood at a normothermic temperature (37° C ± 4° C) is vital in preventing hemolysis and cell damage in the heart 101. The heating / cooling unit 178 includes a heat / cold pad 182 through which heating / cooling fluid flows through. The heat / cold pad 182 is placed on a component of the oxygenator system 200 through which the perfusion fluid flows in order to heat / cool the perfusion fluid to the desired normothermic temperature. The heart EVPS 100 also has a temperature sensor 184 positioned within the perfusion fluid reservoir 156 which detects the temperature of the perfusion fluid within the fluid reservoir 156 and provide a temperature signal corresponding to the detected temperature of the perfusion fluid. A temperature sensor circuitry 185 operably coupled to the temperature sensor 184 may also be provided to condition and / or generate the temperature signal using the temperature sensor 184. The temperature sensor 184 is operably coupled to the data acquisition and control system 162. The heating / cooling unit 178 may also be operably coupled to the data acquisition and control system 162 which is configured to control the heating / cooling unit 178 to control the temperature of the perfusion fluid based on the temperature signal from the temperature sensor 184. In one embodiment, the heating / cooling unit 178 may comprise a Peltier module and electric coils. In still additional aspect, the heating / cooling unit may be lightweight and compact, such as having a maximum weight of 3 kg, and occupying a volume of less than 1000 sq. cm. In yet another aspect, the heating / cooling unit may be is battery-powered. This allows the heart EVPS 100 to be portable and fully self-contained (i.e., operable without connection to any external power source). Alternatively, the heating / cooling unit may be a thermal pump heater / cooler such as the TPS700 sold by Stryker Corp.

[0076] The harvest organ system 10 also has a blood gas monitor 186 which analyzes the circulating perfusion fluid and determines blood gas parameters of the perfusion fluid. The blood gas monitor 186 determines blood gas parameters such as partial pressure of oxygen dissolved oxygen in blood), oxygen saturation (percentage of hemoglobin bound to oxygen), total oxygen content (dissolved + bound to hemoglobin), partial carbon dioxide, pH (blood acidity or alkalinity), bicarbonate, lactate, electrolytes(e.g., sodium, potassium, chlorine, calcium). As an example, the blood gas monitor 186 may be one of the blood parameters monitoring systems sold by Cardiovascular Dynamics, Inc. (CDI), sometimes referred to as a CDI or CDI blood monitor.

[0077] The harvested organ system 10 also has a hemoconcentrator 176 having an inlet connected to the perfusion fluid inlet line 156 and an outlet connected to the perfusion fluid outlet line 122 from the oxygenation system 200. Perfusion fluid flows through the hemoconcentrator 176 and the hemoconcentrator selectively removes certain components, such as water, electrolytes and low-molecular weight substances, from the perfusion fluid circulating through the heart EVPS 100. The net effect of the hemoconcentrator 176 is to increase the concentration of blood cells and other certain other components within the perfusion fluid. As shown in FIG. 3, the hemoconcentrator 176 is a component of the oxygenation system 200, but in an alternative embodiment, the hemoconcentrator 176 may be a component of the heart EVPS 100.

[0078] The data acquisition and control system 162 is configured to receive and store system operating data from the heart EVPS 100 and also to control the operation of the heart EVPS 100. The data acquisition and control system 162 is operably coupled to the fluid level sensor 168, the temperature sensor 174, the heart rate sensor 170, the blood gas monitor 186, the vent pump 132, the heating / cooling unit 178, the pressure sensors 188, the flow sensors 190, and the oxygenation system 200. Optionally, the data acquisition and control system 162 may also be operably coupled to the pacemaker 166 and the defibrillator 168. The data acquisition and control system 162 includes a computer and software which is configured to continuously monitor and store the system data parameters over time during use of harvested organ system 10, including the heart EVPS 100 and oxygenation system 200. The system data parameters include one or more of heart rate, perfusion fluid temperature, perfusion fluid blood gas parameters, perfusion fluid pressures, perfusion flow rates out of the oxygenation system and through the LV vent tube, etc. The system data parameters may also include the operating parameters of the components of the harvested organ system 10, including one or more of the vent pump 132, the pacemaker 166, the defibrillator 168, the oxygenation system 200, the hemoconcentrator 176, etc.

[0079] The continuously monitored and recorded system data parameters during the period of preserving the heart in the heart EVPS 100 allows a clinician and / or physician to review the data and determine if any abnormalities are detected. Proper therapies can then be applied, such as anti-arrhythmic drugs to stabilize heart rhythm, vasopressors to maintainperfusion pressure, manual massage, cannula rearrangement, defibrillation and / or other interventions to treat and optimize the donor heart's condition before transplantation to improve the transplantation outcome.

[0080] The heart EVPS 100 is designed to be as compact and lightweight such that the entire heart EVPS 100 can fit into a backpack or suitcase that can be easily transported and carried. The design of the heart EVPS 100 also minimizes the cord and tube lengths, utilized, enabling system to be compact and lightweight system. For example, the inlet line 154 (venous line 154) and outlet line 122 (arterial line 154) from the heart chamber 102 are short tubes because the heart EVPS 100 can be placed side by side with the oxygenation system 200. to reduce tubing length. In addition, the vent pump 132 utilizes a small roller pump that can be integrated with the heart chamber 102. Furthermore, the hemoconcentrator 176 can attach directly to the heart chamber 104, eliminating the need for long tubing. Thus, in the overall harvest organ system 10, only a few feet of tubing are needed to connect the heart EVPS 100 to the oxygenation system 200, and very little tubing is required for the connections of the vent pump 132 and hemoconcentrator 176. The size of the tubing may vary as the heart EVPS 100 is configured to work with all sizes and types of oxygenation systems 200. The ORGAN CARE SYSTEM™ sold by TransMedics, Inc., comes with long, built-in tubing as well as extra tubing, such that it is limited to a certain tubing size and a large total length of tubing.

[0081] The oxygenation system 200 will now be generally described. The oxygenation system 200 includes a perfusion fluid inlet 202 connected to the inlet line 154. Th oxygenation system also includes an oxygenator 204 which oxygenates perfusion fluid including blood and removes carbon dioxide. For example, in the case that the oxygenation system 200 is an ECMO, the ECMO uses a membrane oxygenation process to oxygenate the perfusion fluid and remove carbon dioxide. As one non-limiting example, the oxygenation system 200 may be a CARDIOHELP™ System sold by Maquet, Inc., which is an ECMO system. The oxygenation system 200 has a fluid pump 206 which pumps the perfusion fluid through the oxygenator 204 and then pumps the oxygenated perfusion fluid out through the fluid outlet 208 of the oxygenation system 200. The oxygenation system 200 has a gas blender 216 and an air tank 210, oxygen tank 212, and a carbon dioxide tank 214 connected to the gas blender 216 to supply the oxygenator with a proper mix of blood gas for oxygenating the perfusion fluid. A blood gas sampling system 218, such as an i-Stat system sold by Abbott, Inc., may also be provided to sample and measure the blood gasparameters of the perfusion fluid. These blood gas parameters may be the same or similar to the blood gas parameters measured by blood gas monitor 186, described herein.

[0082] The heart EVPS 100 is configured to be compatible with most available oxygenation systems 200, including those with continuous flow pumps or other frequently used pumps and oxygenation systems. These systems utilize standard sized tubing and fittings, in which the current standard is 3 / 8”. Accordingly, the heart EVPS 100 includes interfaces to the oxygenation system 200 which fit the standard sized tubing and fittings. In particular, the perfusion fluid outlet port 150 and the external inlet port connector 120 of the heart EVPS 100 which connect to the inlet line 154 and outlet line 122, respectively, are the standard sized fitting and receive the standard sized tubing, currently 3 / 8”. The inlet line 154 and outlet line 122 are the standard sized tubing, currently 3 / 8”. In addition, the perfusion fluid reservoir 156 is size to hold a volume of from 0.25 L to 2.5 L, ensuring stable perfusion flow dynamics through the oxygenation system 200. This reservoir volume meets the minimum reservoir volume required for all currently available oxygenation / ECMO systems.

[0083] The method of connecting the heart EVPS 100 to the oxygenation system 200 and using the harvested organ system 10 to preserve an explanted heart for implantation will now be described. Within a surgical setting (e.g., a surgical room within a hospital, or any other location at which an organ is being explanted from a donor patient), the heart EVPS 100 is connected to the oxygenation system 200. The perfusion fluid outlet port 150 of the heart EVPS 100 is connected to the inlet line 154 which is in fluid communication with a perfusion fluid inlet 202 of the oxygenation system 200. Upon making this connection, the perfusion fluid reservoir 156 within the heart container 104 is fluidly connected to the fluid inlet 202 of the oxygenation system 200. The external inlet port connector 124 of the heart EVPS 100 is connected to the outlet line 122 which is in fluid communication with the perfusion fluid outlet 208 of the oxygenation system 200. Upon making this connection, the outlet 208 of the oxygenation system 200 which outputs oxygenated perfusion fluid is connected to the perfusion fluid inlet port 114.

[0084] The heart platform 180 having the correct height to position the heart 101 in the heart container 104 is selected and placed onto the base 106 within the heart container 104.

[0085] The heart 101 is explanted from the heart donor. The heart 101 to be harvested is surgically accessed, such as by performing a sternotomy. Then, the first end ofthe graft 125 is sutured to the aorta 126 of the heart 101 and the second end of the graft 125 is secured to the internal aorta connector 124 of the top lid 112 of the heart container 104. The LV vent tube 136 is positioned into the heart 101 such that the inlet of the LV vent tube 136 is positioned in the left ventricle 138 and connecting the outlet of the LV vent tube 136 to the internal vent connector 134 of the top lid 112. The heart 101 is surgically removed from the heart donor and placed into the heart container 104 and onto the heart platform 180. The heart 101 may be fully surgically removed from the donor before, after, or during the other steps of the process of explanting the heart 101 and connecting the heart to the heart EVPS 100. The top lid 112 is then secured onto the open top of the middle portion 108 of the heart container 104.

[0086] Then, the heart EVPS 100 and oxygenation system 200 are primed by filling the perfusion fluid reservoir 156 within the heart container 104, the vent pump 132, the oxygenation system 200 and the fluid lines of the harvested organ system 10 with perfusion fluid.

[0087] The heart EVPS 100 and oxygenation system 200 are then operated to perform the heart preservation process. The data acquisition and control system 162 may control the operation of the system 10, and monitor and record the system data parameter during operation of the system 10. Also, during the perfusion process, the pacemaker 166 induces and regulates the beating of the heart 101.

[0088] The oxygenation system 200 pumps perfusion fluid from the fluid reservoir 156 of the heart container 104 out through the perfusion fluid outlet port 150 and into the inlet 202 of the oxygenation system 200. The oxygenator 204 oxygenates the perfusion fluid and pumps the oxygenated perfusion fluid out through the perfusion fluid outlet 208 of the oxygenation system 200. The heating / cooling unit 178 may heat or cool the perfusion fluid as it flows through the oxygenation system 200.

[0089] The oxygenated perfusion fluid from the perfusion fluid outlet 208 flows through the outlet line 122 to the perfusion fluid inlet port 114 of the top lid 112 of the heart container 104, through the graft 125 and into the aorta 126 of the heart 101. The perfusion flow through the heart 101 is retrograde, i.e., in the opposite flow direction to blood flow through the heart when the heart is pumping blood in a human, such that the aorta valve is closed due to the retrograde flow. Hence, the perfusion fluid flows through the myocardium of the heart to the left ventricle 138 and right ventricle 139 of the heart 101. The perfusion fluid flows from the right ventricle and then out through the pulmonary artery 141 of theheart and into the fluid reservoir 156 in the heart container 104. The vent pump 132 pumps the perfusion fluid from the left ventricle 138 through the vent tube 136 and through the vent port 116, then out through the defoamer port 118 and into defoamer 146. The defoamer 146 defoams the perfusion fluid and outlets the defoamed perfusion fluid into the fluid reservoir 156 in the heart container 104.

[0090] Accordingly, the method of using the heart EVPS 100 connected to an oxygenation system 200 to preserve an explanted heart can maintain the explanted heart for an extended period of time, up to 6 hours or more. During this period, the heart can be transported to the recipient patient and the recipient can be prepared for implantation.

[0091] While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents and alternatives falling within the scope of the appended claims.

Claims

WE CLAIM:

1. An ex vivo organ preservation system for connection to an oxygenation system to form an organ perfusion system for preserving a harvested organ, the ex vivo organ preservation system comprising: an organ chamber assembly for containing an ex vivo organ, the organ chamber assembly including an organ container having a base, a wall portion extending upward from the base to an open top of the middle portion, and a top lid configured to fit onto the open top of the middle portion; the top lid having a perfusion fluid inlet port, a vent port, and a defoamer port, the perfusion fluid inlet port having an external inlet port connector configured to be connected to an outlet line from an oxygenation system and an internal organ perfusion connector configured to be connected to an organ in the organ chamber, the vent port having an external vent outlet connector configured to be connected to an inlet of a vent pump and an internal vent connector configured to be connected to an outlet of a vent tube, the defoamer port having an external defoamer connector configured to be connected to an outlet of the vent pump and an internal defoamer connector configured to be connected to a defoamer positioned within the organ container; a perfusion fluid outlet port in one of the wall portion and the base of the organ container, the perfusion fluid outlet port having an internal opening in fluid communication with an inside of the organ container and an external connector configured to be connected to an inlet line to the oxygenation system, such that the organ container is a perfusion fluid reservoir; a vent pump having a vent pump inlet connected in fluid communication with the external vent outlet connector and a vent pump outlet connected in fluid communication with the defoamer port, the vent pump configured to pump perfusion fluid in through the vent tube and out through the defoamer port into the perfusion fluid reservoir within the organ container; and a perfusion fluid level sensor positioned within the organ container, the perfusion fluid level sensor configured to detect a temperature of the perfusion fluid within the organ container and to provide a fluid level signal corresponding to the detected level of perfusion fluid.

2. The ex vivo organ preservation system of claim 1, further comprising:the defoamer positioned within the organ container, the defoamer operably connected to the internal defoamer connector, wherein the defoamer is configured to reduce foam in the perfusion fluid as it flows out of the defoamer and into the organ container.

3. The ex vivo organ preservation system of claim 1, further comprising: a hemoconcentrator connected between the perfusion fluid outlet port and the perfusion fluid inlet port, the hemoconcentrator configured to selectively remove certain components from the perfusion fluid circulating through the ex vivo organ preservation system.

4. The ex vivo organ preservation system of any one of claims 1-3, further comprising: a defibrillator having defibrillator contacts for insertion inside the organ container for placement in contact with the organ, the defibrillator configured to deliver a controlled electric shock to the organ; and wherein the top lid includes one or more defibrillator openings for providing access for the defibrillator contacts to be inserted inside the organ container, and one or more adjustable covers configured to open and close the defibrillator openings.

5. The ex vivo organ preservation system of claim 4, wherein the adjustable covers are sliding windows.

6. The ex vivo organ preservation system of any one of claims 1-3, further comprising: a pacemaker configured to regulate a function of an organ being preserved in the organ container of the ex vivo organ preservation system; a heart rate sensor configured to detect a heart rate of a harvested organ being preserved in the ex vivo organ preservation system and provide a heart rate signal corresponding to the detected heart rate; and wherein the top lid includes a pacemaker port for providing access for pacemaker electrode and lead wires into the organ container.

7. The ex vivo organ preservation system of any one of claims 1-3, further comprising: a compact heating / cooling unit for controlling the temperature of the perfusion fluid, the heating / cooling unit configured to heat and cool the perfusion fluid; a temperature sensor positioned within the organ container, the temperature sensor configured to detect a temperature of the perfusion fluid within the organ container and provide a temperature signal corresponding to the detected temperature of the perfusion fluid; and wherein the ex vivo organ preservation system is configured to control the temperature of the perfusion fluid using the heating / cooling unit based on the temperature signal.

8. The ex vivo organ preservation system of claim 7, wherein the heating / cooling unit comprises a Peltier module and electric coils, weighs less than 3 kg and occupies a volume of less than 1000 sq. cm.

9. The ex vivo organ preservation system of any one of claims 7, wherein the heating / cooling unit is battery-powered.

10. The ex vivo organ preservation system of any one of claims 7, wherein the heating / cooling unit comprises a heating / cooling pad configured to be placed in contact with a component of one of the ex vivo organ preservation system and the oxygenation system to heat and cool the perfusion fluid.

11. The ex vivo organ preservation system of any one of claims 1-3, further comprising: a blood gas monitor configured to sample the perfusion fluid and determine blood gas parameters of the perfusion fluid.

12. The ex vivo organ preservation system of any one of claims 1-3, further comprising: a plurality of organ platforms each configured to be individually positioned within the organ container to support an organ placed onto the organ platform, each organ platform having a different height to accommodate different size organs within the organ container,such that one of the plurality of organ platforms is selected based on a size of the organ and placed into the organ container to support the organ within the organ container.

13. The ex vivo organ preservation system of any one of claims 1-3, wherein the ex vivo organ preservation system is configured to preserve a pediatric heart from a donor weighing less than 40 kg, and wherein the organ container has a diameter of from 10 cm to 14 cm and a height of from 10 cm to 15 cm.

14. The ex vivo organ preservation system of any of claims 1-3, further comprising: a data acquisition system operably coupled to each of the sensors and configured to continuously monitor and store parameters of the ex vivo organ preservation system and organ being preserved therein during use of the ex vivo organ preservation system.

15. The ex vivo organ preservation system of claim 1, further comprising: a heart rate sensor configured to be connected to the organ and to detect a heart rate of the organ and provide a heart rate signal corresponding to the detected heart rate; a temperature sensor configured to detect a temperature of the perfusion fluid within the organ container and provide a temperature signal corresponding to the detected temperature of the perfusion fluid; a blood gas monitor configured to sample the perfusion fluid and determine blood gas parameters of the perfusion fluid; a pressure sensor configured to detect a pressure of the perfusion fluid and provide a pressure signal corresponding to the detected pressure; and a data acquisition system operably coupled to the fluid level sensor, the temperature sensor, the blood gas monitor, and the pressure sensor and configured to continuously monitor and store the heart rate, temperature, blood gas parameters, and perfusion fluid pressure over time during use of the ex vivo organ preservation system. 16.method of using the ex vivo organ preservation system according to any one of claims 1-15, the method comprising: within a surgical setting, connecting the ex vivo organ preservation system to an oxygenation system by a process including:connecting the perfusion fluid outlet port to an inlet line in fluid communication with a perfusion fluid inlet of the oxygenation system; and connecting the external inlet port connector to an outlet line in fluid communication with a perfusion fluid outlet of the oxygenation system; wherein the oxygenation system is configured to receive perfusion fluid via the perfusion fluid inlet, oxygenate the perfusion fluid, and output the oxygenated perfusion fluid out through the perfusion fluid outlet; explanting an organ from an organ donor via a process including: surgically accessing the organ to be harvested; suturing a first end of a graft to a blood vessel of the organ and securing a second of the graft to the internal organ perfusion connector; positioning a vent tube into the organ such that an inlet of the vent tube is positioned at a venting location at which perfusion fluid is intended to flow through the organ and connecting an outlet of the vent tube to the internal vent connector; surgically removing the organ from the organ donor and placing the organ into the organ container; securing the top lid onto the open top of the middle portion; priming the ex vivo organ preservation system and oxygenation system by filling the organ container, vent pump, oxygenation system and fluid lines with perfusion fluid; operating the ex vivo organ preservation system and oxygenation system to perform a process comprising: the oxygenation system pumping perfusion fluid from the fluid reservoir of the organ container out through the perfusion fluid outlet port and into the oxygenation system, the oxygenation system oxygenating the perfusion fluid and pumping the oxygenated perfusion fluid out through the perfusion fluid outlet of the oxygenation system; the oxygenated perfusion fluid from the perfusion fluid outlet flowing through the perfusion fluid inlet port of the top lid of the organ container, through the graft into the blood vessel of the organ and then through blood vessel branches of the organ and to the venting location; and the vent pump pumping the perfusion fluid through the vent tube and through the vent port, then out through the defoamer port and into the fluid reservoir in the organ container.

17. An ex vivo heart preservation system for connection to an oxygenation system to form a heart perfusion system for preserving a harvested heart, the ex vivo heart preservation system comprising: a heart chamber assembly for containing an ex vivo heart, the heart chamber assembly including a heart container having a base, a wall portion extending upward from the base to an open top of the middle portion, and a top lid configured to fit onto the open top of the middle portion; the top lid having a perfusion fluid inlet port, a left ventricle (LV) vent port, and a defoamer port, the perfusion fluid inlet port having an external inlet port connector configured to be connected to an outlet line from an oxygenation system and an internal aorta connector configured to be connected to an aorta of a harvested heart placed in the organ chamber, the LV vent port having an external vent outlet connector configured to be connected to an inlet of a vent pump and an internal vent connector configured to be connected to an outlet of an LV vent tube, the LV vent tube configured to be inserted into a left ventricle of the harvested heart, the defoamer port having an external defoamer connector configured to be connected to an outlet of the vent pump and an internal defoamer connector configured to be connected to a defoamer positioned within the organ container; a perfusion fluid outlet port in one of the wall portion and the base of the heart container, the perfusion fluid outlet port having an internal opening in fluid communication with an inside of the heart container and an external connector configured to be connected to an inlet line to the oxygenation system, such that the heart container is a perfusion fluid reservoir; a vent pump having a vent pump inlet connected in fluid communication with the defoamer port and a vent pump outlet connected in fluid communication with the internal vent connector, the vent pump configured to pump perfusion fluid in through the vent tube and out through the defoamer port into the defoamer and out of the defoamer into the perfusion fluid reservoir within the heart container; and a perfusion fluid level sensor positioned within the organ container, the perfusion fluid level sensor configured to detect a temperature of the perfusion fluid within the heart container and to provide a fluid level signal corresponding to the detected level of perfusion fluid.

18. The ex vivo heart preservation system of claim 17, further comprising: the defoamer positioned within the organ container, the defoamer operably connected to the internal defoamer connector, wherein the defoamer is configured to reduce foam in the perfusion fluid as it flows out of the defoamer and into the organ container.

19. The ex vivo heart preservation system of claim 17, further comprising: a hemoconcentrator connected between the perfusion fluid outlet port and the perfusion fluid inlet port, the hemoconcentrator configured to selectively remove certain components from the perfusion fluid circulating through the ex vivo heart preservation system.

20. The ex vivo organ preservation system of any one of claims 17-19, further comprising: a defibrillator having defibrillator contacts for insertion inside the heart container for placement in contact with the heart placed in the heart container, the defibrillator configured to deliver a controlled electric shock to the heart; and wherein the top lid includes one or more defibrillator openings for providing access for the defibrillator contacts to be inserted inside the heart container, and one or more adjustable covers configured to open and close the defibrillator openings.

21. The ex vivo organ preservation system of claim 20, wherein the adjustable covers are sliding windows.

22. The ex vivo heart preservation system of any one of claims 17-19, further comprising: a pacemaker configured to regulate a heart rate of the heart being preserved in the heart container; and wherein the top lid includes a pacemaker port for providing access for pacemaker electrode and lead wires into the heart container.

23. The ex vivo organ preservation system of any one of claims 17-19, further comprising:a compact heating / cooling unit for controlling the temperature of the perfusion fluid, the heating / cooling unit configured to heat and cool the perfusion fluid; a temperature sensor positioned within the heart container, the temperature sensor configured to detect a temperature of the perfusion fluid within the heart container and provide a temperature signal corresponding to the detected temperature of the perfusion fluid; and wherein the ex vivo heart preservation system is configured to control the temperature of the perfusion fluid using the heating / cooling unit based on the temperature signal.

24. The ex vivo heart preservation system of claim 23, wherein the heating / cooling unit comprises a Peltier module and electric coils, weighs less than 3 kg and occupies a volume of less than 1000 sq. cm.

25. The ex vivo heart preservation system of any one of claims 23, wherein the heating / cooling unit is battery-powered.

26. The ex vivo heart preservation system of any one of claims 23, wherein the heating / cooling unit comprises a heating / cooling pad configured to be placed in contact with a component of one of the ex vivo heart preservation system and the oxygenation system to heat and cool the perfusion fluid.

27. The ex vivo heart preservation system of any one of claims 17-19, further comprising: a blood gas monitor configured to sample the perfusion fluid and determine blood gas parameters of the perfusion fluid.

28. The ex vivo heart preservation system of any one of claims 17-19, further comprising: a plurality of heart platforms each configured to be individually positioned within the organ container to support a heart placed onto the heart platform, each heart platform having a different height to accommodate different size hearts within the heart container, such that one of the plurality of heart platforms is selected based on a size of the heart and placed into the heart container to support the heart within the heart container.

29. The ex vivo heart preservation system of any one of claims 17-19, wherein the ex vivo heart preservation system is configured to preserve a pediatric heart from a donor weighing less than 40 kg, and wherein the heart container has a diameter of from 10 cm to 14 cm and a height of from 10 cm to 15 cm.

30. The ex vivo heart preservation system of any of claims 17-19, further comprising: a data acquisition system operably coupled to each of the sensors and configured to continuously monitor and store parameters of the ex vivo heart preservation system and heart being preserved therein during use of the ex vivo heart preservation system.

31. The ex vivo heart preservation system of claim 17, further comprising: a heart rate sensor configured to be connected to the heart and to detect a heart rate of the heart and provide a heart rate signal corresponding to the detected heart rate; a temperature sensor configured to detect a temperature of the perfusion fluid within the heart container and provide a temperature signal corresponding to the detected temperature of the perfusion fluid; a blood gas monitor configured to sample the perfusion fluid and determine blood gas parameters of the perfusion fluid; a pressure sensor configured to detect a pressure of the perfusion fluid and provide a pressure signal corresponding to the detected pressure; and a data acquisition system operably coupled to the fluid level sensor, the temperature sensor, the blood gas monitor, and the pressure sensor and configured to continuously monitor and store the heart rate, temperature, blood gas parameters, and perfusion fluid pressure over time during use of the ex vivo organ preservation system.

32. A method of using the ex vivo heart preservation system according to any one of claims 17-31, the method comprising: within a surgical setting, connecting the ex vivo heart preservation system to an oxygenation system by a process including: connecting the perfusion fluid outlet port to an inlet line in fluid communication with a perfusion fluid inlet of the oxygenation system; andconnecting the external inlet port connector to an outlet line in fluid communication with a perfusion fluid outlet of the oxygenation system; wherein the oxygenation system is configured to receive perfusion fluid via the perfusion fluid inlet, oxygenate the perfusion fluid, and output the oxygenated perfusion fluid out through the perfusion fluid outlet; explanting a heart from a heart donor via a process including: performing a sternotomy to surgically access the heart to be harvested; suturing a first end of a graft to an aorta of the heart and securing a second of the graft to the internal aorta connector; positioning a vent tube into the heart such that an inlet of the vent tube is positioned within the left ventricle of the heart and connecting an outlet of the vent tube to the internal vent connector; surgically removing the heart from the heart donor and placing the organ into the heart container; securing the top lid onto the open top of the middle portion; priming the ex vivo heart preservation system and oxygenation system by filling the organ container, vent pump, oxygenation system and fluid lines with perfusion fluid; operating the ex vivo heart preservation system and oxygenation system to perform a process comprising: the oxygenation system pumping perfusion fluid from the fluid reservoir of the heart container out through the perfusion fluid outlet port and into the oxygenation system, the oxygenation system oxygenating the perfusion fluid and pumping the oxygenated perfusion fluid out through the perfusion fluid outlet of the oxygenation system; the oxygenated perfusion fluid from the perfusion fluid outlet flowing through the perfusion fluid inlet port of the top lid of the heart container, through the graft into the aorta of the heart and then through myocardium of the heart and to the left ventricle and right ventricle of the heart, the perfusion fluid flowing from the right ventricle out through a pulmonary artery of the heart and into the fluid reservoir in the heart container; and the vent pump pumping the perfusion fluid from the left ventricle through the vent tube and through the vent port, then out through the defoamer port and into the fluid reservoir in the heart container.

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