ORGAN PERFUSION SYSTEM AND METHOD

Abstract

An organ perfusion system (100) for extracorporeal perfusion of a heart (1) includes an organ chamber (15) having an aortic connector (17), and a first fluid flow path (19) comprising a pump interface (23) and an oxygenator (25), the aortic connector being fluidly connected to the first fluid flow path. The system is adapted for use in a method, wherein oxygenated perfusate is flowed into the heart via the aorta and desoxygenated perfusate is allowed to exit the heart via the inferior vena cava and/or the superior vena cava to thereby perfuse the heart in a substantially unloaded state. Such method may allow for improved recovery of the heart tissue during perfusion. The organ perfusion system may further comprise a perfusate reservoir (27) and/or a chassis, wherein the organ chamber is pivotable with respect to the chassis for holding the heart in a tilted position or to allow rotation of the organ chamber in a horizontal plane.

Claims

1. A method of extracorporeal perfusion of a heart, the method comprising steps of: providing a heart perfusion system comprising an organ chamber having an aortic connector, and a first fluid flow path comprising a pump interface and an oxygenator, the aortic connector being fluidly connected to the first fluid flow path; placing the heart within the organ chamber and attaching an aorta of the heart to the aortic connector; providing a pump to transfer pumping force to the pump interface to pump venous perfusate within the first fluid flow path via the oxygenator to thereby provide subsequent flow of oxygenated perfu sate to the heart via the aortic connector; and allowing perfusate to exit the heart via one or more of the inferior vena cava and the superior vena cava to thereby perfuse the heart in a substantially unloaded state.

2. The method according to claim 1 including a step of providing a left ventricle venting arrangement comprising one or more ducts, and locating the one or more ducts within the left ventricle of the heart to vent perfusate from the left ventricle.

3. The method according to claim 2 including a step of directing the vented perfusate to a perfusate reservoir of the heart perfusion system.

4. The method according to claim 1 wherein the perfusate is at a temperature of between about 4° C. and about 34° C.

5. The method according to claim 1 wherein the perfusate is pumped at a constant pressure between about 30 and 100 mmHg.

6. The method according to claim 5 wherein the pump is a centrifugal pump.

7. The method according to claim 1 where the perfusate is supplied to the aorta of the heart at a volume rate of about 75 mls/min to about 1300 mls/min.

8. The method according to claim 1 wherein the perfusate is oxygenated using a gaseous mix of about 95% air to about 5% carbon dioxide.

9. The method according to claim 1 wherein the method includes further steps of monitoring a vascular resistance index of the heart.

10. The method according to claim 1 wherein the method includes further step of monitoring myocardial oxygen consumption of the heart.

11. A heart perfusion system for extracorporeal perfusion of a heart, the system comprising: an organ chamber having an aortic connector for connection to an aorta of the heart, the aortic connector being fluidly connected to a first fluid flow path comprising a pump interface and an oxygenator; and wherein the pump interface is arranged to, in use, transfer a pumping force from a pump to pump venous perfusate via the oxygenator to thereby provide subsequent flow of oxygenated perfusate to the heart via the aortic connector of the organ chamber, whereby the extracorporeal perfusion system is configured for use in the method of extracorporeal heart perfusion set out in claim 1.

12. The heart perfusion system of claim 11 wherein the first fluid flow path further comprises a perfusate reservoir.

13. The heart perfusion system of claim 12 wherein the perfusate reservoir is located intermediate the organ chamber and the pump interface on the first fluid flow path.

14. The heart perfusion system of claim 11 wherein the heart perfusion system comprises a left ventricle venting arrangement comprising one or more ducts configured to, in use, vent perfusate from the left ventricle of the heart.

15. The heart perfusion system of claim 14 wherein the one or more ducts are configured to direct the vented perfusate to a perfusate reservoir.

16. The heart perfusion system according to claim 11 wherein the heart perfusion system comprises a portable chassis.

17. The heart perfusion system according to claim 16 wherein the largest dimension of the heart perfusion system is less than about 55 cm.

18. The heart perfusion system according to claim 16 wherein the organ chamber is pivotable with respect to the chassis.

19. The heart perfusion system according to claim 18 wherein the organ chamber is pivotable with respect to the chassis to thereby allow movement of the organ chamber between a first position, in which the organ chamber is configured to hold a heart in a substantially horizontal position, and a second position in which the organ chamber is configured to hold a heart in tilted position.

20. The heart perfusion system according to claim 18 wherein the organ chamber is pivotable with respect to the chassis to thereby allow rotation of the organ chamber in a horizontal plane with respect to the chassis, optionally to allow rotation of the organ chamber by up to 90° with respect to the chassis.

21. The heart perfusion system according to claim 11 wherein the aortic connector comprises at least one attachment point for attachment of sutures, optionally wherein the at least one attachment point comprises a through-hole formed in the aortic connector.

22. The heart perfusion system according to claim 11 wherein the pump is a centrifugal pump operable to pump perfusate at a constant pressure of between about 30 and 100 mmHg.

23. The heart perfusion system according to claim 11 wherein the heart perfusion system comprises a single use disposable module and a multiple-use module, at least the organ chamber and the first fluid flow path forming part of the single use disposable module, and the pump forming a part of the multiple-use module, and wherein the single use disposable module is configured to engage with the multiple-use module for electromechanical interoperation.

Description

SUMMARY OF THE FIGURES

[0045] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0046] FIG. 1 is a schematic (simplified) drawing of a heart.

[0047] FIG. 2 is a schematic drawing showing a heart perfusion system according to the invention.

[0048] FIG. 3 is a schematic drawing showing a heart perfusion system according to the invention, the heart perfusion system comprising a left ventricle venting arrangement.

[0049] FIG. 4 is a schematic drawing of part of the left ventricle venting system shown in FIG. 3.

[0050] FIG. 5 is an image showing a portion of a heart perfusion system according to the invention.

[0051] FIG. 6 is an image showing an aortic connector of a heart perfusion system according to the invention.

[0052] FIG. 7 is an image showing a heart perfusion system according to the invention.

[0053] FIG. 8 is an image showing a portion of a heart perfusion system according to the invention.

[0054] FIG. 9 is a schematic drawing showing (a) the organ chamber in a first (horizontal) position and (b) a second (tilted) position.

DETAILED DESCRIPTION OF THE INVENTION

[0055] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0056] The basic anatomy of a heart 1 will be briefly described in relation to FIG. 1. The heart 1 comprises four chambers, two (right atrium 2 and right ventricle 3) on the right side of the heart, and two (left atrium 4 and left ventricle 5) on the left side of the heart. During normal function of a heart in-vivo, blood enters the heart via the atria, and is pumped out by the ventricles. The right side of the heart pumps deoxygenated (venous) blood from the right ventricle 3 to the lungs, via the pulmonary artery 6. Blood passes through the lungs, where it is oxygenated, before returning to the heart via the pulmonary veins 7. The oxygenated blood enters the left atrium 4 of the heart, passes through the mitral valve 8 into the left ventricle 5, whereby it is pumped out of the heart via the aorta 9 to supply the body with oxygenated blood. Deoxygenated blood returns to the right atrium 2 of the heart via the superior vena cava 10, the inferior vena cava 11 and the coronary sinus 12, whereby it passes through the tricuspid valve 13 into the right ventricle 3.

[0057] FIG. 2 is a schematic drawing showing a heart perfusion system 100 according to one embodiment of the invention. The system comprises an organ chamber 15 configured for containing a heart. Further details of the organ chamber will be discussed below in relation to FIG. 5. The organ chamber 15 comprises an aortic connector 17 for connection to an aorta of the heart. Further features of the aortic connector are discussed below in relation to FIG. 6. The aortic connector is not shown in FIG. 2, however its location is clearly indicated: the aortic connector is an inlet to the organ chamber. The organ chamber 15 further comprises an outlet 16.

[0058] The heart perfusion system 100 comprises a first fluid flow path 19, along which, in use, perfusate 21 flows, as indicated by arrows in FIG. 2. At least portions of the first fluid flow path may be defined by ducting arranged to allow perfusate to flow through said ducting. The first fluid flow path comprises a pump interface 23 which is arranged to, in use, transfer a pumping force from a pump to pump venous perfusate around the first fluid flow path. In preferred arrangements, the pump is a centrifugal pump. For example, one pump suitable for use in the present system is the Medos Deltastream™ centrifugal pump. This pump comprises a pump head (or ‘pump interface’ as described in relation to the present invention) and a pump body. The pump head comprises a housing having an approximately conical inlet portion, a main body, and an outlet. The main body of the housing contains a rotor portion (impeller) of the centrifugal pump, which is magnetically driven. The outlet of the housing is disposed at about 90-100° relative to the inlet of the housing. Perfusate enters the pump head via the conical inlet, whereby a pumping force is translated to the perfusion fluid via the impeller, to thereby pump the perfusion fluid out of the pump head via the outlet, and onwardly around the first fluid path to the organ chamber assembly.

[0059] The first fluid flow path further comprises an oxygenator 25 configured to oxygenate perfusate passing through the oxygenator. The oxygenator 25 is disposed downstream of the pump interface 23 on the first fluid flow path, such that the pump interface pumps perfusate via the oxygenator to thereby provide subsequent flow of oxygenated perfusate to the heart via the aortic connector 17 of the organ chamber. Due to this arrangement, the perfusion system is configured such that the system is not reliant on normal loading of one or more of the ventricles of heart to pump venous perfusate to the oxygenator, in other words, the system is configured to perfuse the heart in a substantially unloaded state.

[0060] The first fluid flow path further comprises a perfusate reservoir 27 for holding a volume of perfusate 21. In typical arrangements the perfusate reservoir 27 is configured to hold a reservoir volume of between 200 ml and 2000 ml of perfusate. The perfusate reservoir is disposed intermediate the organ chamber 15 and the pump interface 23 on the first fluid flow path 19.

[0061] The first fluid flow path 19 can be divided into a deoxygenated flow portion, and an oxygenated flow portion. The deoxygenated flow portion is indicated in FIG. 2 by dashed arrows, and is a portion defined downstream of the organ chamber and upstream of the oxygenator on the first fluid flow path. The oxygenated flow portion is indicated in FIG. 2 by solid arrows, and is defined downstream of the oxygenator and upstream of the organ chamber on the first fluid flow path. Accordingly, in this arrangement, the reservoir and pump interface form part of the deoxygenated flow portion of the first fluid flow path 19.

[0062] In use, a heart 1 is positioned in the organ chamber 15 and fluidly connected to the first fluid flow path 19 of the heart perfusion system 100 by connection of the aorta 9 of the heart to the aortic connector 17 of the organ chamber. The aorta may be attached by suturing the aorta 9 of the heart to attachment points of the aortic connector, as discussed below in relation to FIG. 6. Oxygenated perfusate is flowed into the heart via the aorta, whereby the heart muscle is perfused via the coronary vasculature of the heart (not pictured). Venous/deoxygenated perfusate then flows into the right atrium 2 of the heart 1 via the coronary sinus 12. Perfusate is allowed to exit the heart via one or more of the inferior vena cava (IVC) and the superior vena cava (SVC)—here by leaving the IVC and SVC unsutured during perfusion. In this way, deoxygenated perfusate can drain directly from the right atrium 2 via the IVC or SVC, as indicated by arrows in FIG. 2. According there is significantly reduced flow into the right ventricle during perfusion in comparison to known perfusion arrangements. However, some perfusate may pass into the right ventricle 3, whereby it is allowed to exit the heart via the pulmonary artery 6, as indicated by a further arrow in FIG. 2. Here, perfusate from the IVC, SVC and pulmonary artery vents directly into the organ chamber 15. Perfusate can exit the organ chamber 15 via outlet 16, which is fluidly connected to the perfusate reservoir 27. With this arrangement, it is possible to perfuse a heart without provision of complicated venting arrangements for directing perfusate.

[0063] In some systems, a left ventricle venting arrangement is provided. A system comprising a left ventricle venting arrangement is shown in FIG. 3. Here, a duct 29 is located within the left ventricle 5 of the heart (e.g. by being arranged to pass through the left atrial appendage into the left ventricle via the mitral valve)to thereby vent perfusate from the left ventricle. Venting the left ventricle can help to prevent distention and/or injury of the left ventricle during perfusion. FIG. 4 shows a tip portion 30 of the duct 29. The duct comprises a plurality of perforations 31 along the length of the duct to thereby allow perfusate to enter the duct at multiple locations. In the arrangement shown in FIG. 3, the left ventricle venting arrangement is configured to direct the perfusate vented from the left ventricle to the perfusate reservoir 27 of the heart perfusion system. In other words, the perfusate is not vented directly into the organ chamber 15. Instead, the left ventricle venting arrangement provides a second fluid flow path which bypasses the organ chamber. Perfusate vented from the left side of the heart via the left ventricle will typically be oxygenated perfusate which has entered the left side of the heart via a trickle flow from the aorta. Accordingly by directing this vented oxygenated perfusate to bypass the organ chamber, whilst venous perfusate is vented directly into the organ chamber, it is possible to measure the myocardial oxygen consumption sufficiently accurately, by providing a first oxygen saturation sensor 33 at the inlet 17 to the organ chamber which is arranged to measure oxygen saturation of oxygenated perfusate entering the aorta of the heart, and a second oxygen saturation sensor 34 at the outlet 16 of the organ chamber arranged to measure oxygen saturation of venous perfusate exiting the right side (right atrium and/or right ventricle) of the heart. The myocardial oxygen consumption can be calculated by comparing an output of the first oxygen saturation sensor and an output of the second oxygen saturation sensor.

[0064] The arrangement shown in FIG. 3 further comprises temperature regulation means arranged to regulate the temperature of perfusate within the first fluid flow path. Here, the temperature regulation means is conveniently provided in the form of a heat exchanger 35 operable to regulate the temperature of perfusate within the oxygenator 25. A jacket is fitted around the oxygenator, and a heated/cooled fluid is passed through the jacket, whereby heat exchanges with the perfusate such that the temperature of perfusate within the first fluid flow path is regulated. In preferred arrangements, the temperature of the perfusate is regulated to be in a range of below 34° C. to keep the metabolic rate of the heart suitably low during perfusion.

[0065] FIG. 5 shows the organ chamber 15 in more detail. The organ chamber comprises a housing 37 and a lid 39. The housing comprises a floor 41, upon which the heart is supported in use, and a perimeter wall 43 upstanding from the floor, and thereby defining an opening via which the heart can be disposed in the housing. When shut, the lid 39 covers substantially the entire opening of the housing. The organ chamber has dimensions of approximately L345 mm×H233 mm×W215 mm, and may be conveniently produced by any suitable method including e.g. 3D printing or injection moulding. The material of the organ chamber is contact-biocompatible—conveniently it is made from Tritan™ plastic, although a wide range of other materials may be suitable. The aortic connecter 17 (shown in more detail in FIG. 6) provides an inlet to the organ chamber. The outlet 16 of the organ chamber is disposed within a well portion 38 defined by the floor of the organ chamber (an increased depth portion of the organ chamber)—this is also shown more clearly in FIG. 9. Perfusate vented into the organ chamber will collect in the well portion, whereby it can flow out of the organ chamber via the outlet 16.

[0066] A left ventricle venting arrangement is provided in the form of a duct 29 disposed within the organ chamber, configured for location in the left ventricle of the heart during perfusion. The duct is arranged to pass through the wall 43 of the organ chamber, to avoid obstructing the lid of the organ chamber. The duct is arranged to direct vented fluid to the reservoir 27.

[0067] As shown in FIG. 6, the aortic connector 17 comprises a tube portion 18 and a collar portion 20. A plurality of attachment points are provided in the form of through-holes 22 on the collar portion. The aorta of the heart being perfused can be attached to the aortic connector by suture passing through both the aorta and through the through-holes 22. This can help to prevent the heart from falling off of the aortic connector during perfusion. As there are a plurality of through-holes disposed at approximately equal intervals about a circumference of the aortic connector, the heart can be attached to the connector by sutures disposed at approximately equal intervals about the aorta of the heart. This can provide for more even distribution of force about the circumference of the aorta of the heart when attached to the aortic connector.

[0068] FIG. 7 shows a perspective view of the heart perfusion system including a chassis 45 of the heart perfusion system. The chassis comprises a frame structure 47 to which other components of the heart perfusion system may be attached or on which other components of the heart perfusion system may be supported. The chassis comprises two pairs of handles 49 respectively attached at opposite ends of the frame structure of the chassis. The chassis is here supported on a wheeled base 51 for ease of transportation. The chassis further supports a monitor 63 which is configured to display output information of one or more sensors of the heart perfusion system, for example, oxygen saturation sensors, pressure sensors, temperature sensors, flow rate sensors, oxygen saturation sensors and/or haematocrit sensors (not shown). This can assist an operator in monitoring operation of the system during perfusion.

[0069] The chassis comprises an organ chamber support member 53 configured to support the organ chamber 15. Here, the organ chamber support member 53 is conveniently formed as a cradle into which the organ chamber housing 37 can be fitted. The organ chamber support member is pivotable relative to the chassis to thereby allow movement of the organ chamber between a first position, in which the organ chamber is configured to hold a heart in a substantially horizontal position, and a second position in which the organ chamber is configured to hold a heart in tilted position. FIG. 9 is a schematic drawing showing (a) the organ chamber in the first position (in a horizontal plane, indicated by a dashed line) and (b) the second position, where the organ chamber is tilted at an angle of X° relative to the horizontal plane, as measured along a longitudinal axis of the organ chamber, also indicated by a dashed line. This pivotability is achieved by attaching the organ chamber support member to the chassis via a pivotable hinge, 63.

[0070] The organ chamber support member 53 is also rotatable relative to the chassis as it is disposed on a platform 55 rotatably fixed to the chassis, shown most clearly in FIGS. 7 and 8. The platform is rotatable in a horizontal plane by 90° with respect to the chassis, between a first rotational position (shown in FIG. 7) and a second rotational position (shown in FIG. 8). This is particularly advantageous for performing CT coronary angiography of a heart being perfused in the heart perfusion system, because it is possible to obtain different views of the heart without removing the heart perfusion system from the CT machine.

[0071] The chassis further comprises a reservoir support member 57 and a pump support member 59 which are also disposed on the rotatable platform 55. In this way, the organ chamber, the perfusate reservoir and the pump can be simultaneously rotated with respect to the chassis. This can help to avoid entanglement of different components of the heart perfusion system as the platform 55 is rotated with respect to the chassis.

[0072] A locking member 61 is provided on the chassis configured to lock the rotatable platform in one or other of the first and second rotational positions. This is beneficial to prevent unwanted movement of the rotatable platform during perfusion. Here, the locking member is conveniently provided as a spring-biased pin arranged to interlock with one or more locating holes or recesses formed in the rotatable platform. However, a wide range of alternative locking systems are contemplated.

[0073] The heart perfusion system shown and discussed in relation to FIG. 3-9 comprises a single use disposable module and a multiple-use module. The single-use disposable module includes the organ chamber 15, the ducting which forms path of the first fluid flow path 19, the perfusate reservoir 27, the pump interface 23, the oxygenator 25 and the left ventricle venting arrangement. In other words, all perfusate-contacting components of the heart perfusion system.

[0074] Components forming part of the multiple-use module include (but are not limited to) the pump, the chassis 45 (including frame 47, organ chamber support member 53, platform 55, reservoir support member 57, pump support member 59 etc.) the gas supply source, sensors and the monitor 61 of the heart perfusion system.

[0075] In this way it may be possible to provide a system whereby low-cost portions of the system are single-use, e.g. for reasons of sterility, but wherein higher-cost portions of the system are multiple-use. The system may be provided as a kit which includes a single multiple-use module, and a plurality of single use disposable modules.

[0076] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0077] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0078] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0079] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0080] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0081] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example +/−10%.