Lung ex VIVO preservation with lung rotation

Abstract

A system for ex-vivo preservation of a lung where the lung is supported by a flexible membrane supported by a rotatable receptacle. The flexible membrane and rotatable receptacle may be disposed in an airtight, temperature-controlled case. The lung is coupled to a ventilator to control inflation and a perfusion loop to supply perfusate to the lung.

Description

LUNG EX VIVO PRESERVATION WITH LUNG ROTATIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to US provisional application serial no. 63 / 664,808, filed on June 27, 2024, which is incorporated herein by reference.FIELD OF THE INVENTION

[0002] The application relates generally to an apparatus for supporting a lung during ex-vivo preservation, a system for preserving a lung ex-vivo that included this apparatus, and a method of preserving a lung ex-vivo that utilizes the apparatus and / or the system. The application relates more particularly to an apparatus, system and method wherein the lung is rotated to help blood circulation inside the lung, reduce damage, necrosis, and / or bruising of lung tissue.BACKGROUND OF THE INVENTION

[0003] Lung transplantation offers the only treatment option for many people with life threatening end stage lung disease. However, many patients die waiting for available donor lungs due to the shortage of donor organs. Also, most (over 80%) donor lungs are considered poor quality and unsuitable for transplantation.

[0004] Current organ preservation techniques are short term (under 6 hours) and limiting. A new commercial technology called "ex vivo lung perfusion" (EVLP) preserves donor lungs for up to 24 hours prior to transplant (Transmedics, XVIVO). The EVLP system circulates blood and ventilates oxygen to the lungs outside the body. Furthermore, rej ected donor lungs can be evaluated and treated with drugs in an EVLP system.

[0005] However, there may still shortcomings to EVLP systems. For example, the lungs are usually laid on a hard and smooth surface of the bottom shell inside of a chamber. After several hours, the bottom of the lung often show tissue damage. Also, upon exiting the lung vasculature, the blood flows into the bottom shell and forms a puddle around the lung where the blood comes into contact with air, potentially increasing the risk of infection.

[0006] In view of the foregoing, there is a need for an apparatus, system and method for preserving a lung ex-vivo, wherein the lung can be rotated. Preferably, the system includes the apparatus that allows for lung rotation and a blood perfusion loop that is closed to air .SUMMARY

[0007] The disclosure generally describes a device and a method that can be used to preserve donor lungs. Preserving donor lungs may be required for transplantation, drug research by pharmaceutical companies, or basic research by research institutions.

[0008] A lung may be laid in a flexible and tight-knit net capsule in the chamber. Unlike in some prior art where lung tissue damage is caused by the lung lobes being laid on an excessively hard surface, the flexible and tight-knit net may be used to gently support the lung in a chamber. As such, the lung may be less deformed, the vasculature of the lung may be less compressed, thus potentially reducing bruise / edema occurrence, increasing the duration of lung viability ex vivo to more than twenty -four hours.

[0009] The flexible and tight-knit net capsule may be attached to a rotary holder so that the flexible and tight-knit net capsule and the lung supported by it can be rotated. The rotation of the lung may substantially reduce bruising / edema on the lungs caused by the effects of long-term weight bearing on the bottom shell of the chamber still further. For example, the lung may be laid on the flexible and tight-knit net capsule and rotated continuously or at defined intervals (e.g., every couple of hours).

[0010] The entire perfusate circulatory system (the perfusion loop and the lung vasculature) may be devoid of any perfusate-and-ambient air interface. Unlike in some prior art where the perfusate (e.g., typically blood) is at least partially exposed to ambient air present within a lung preservation chamber when the perfusate exits the lung and flows in a collection reservoir, the perfusate is preferably contained in a hermetically closed perfusion loop to exclude contact with ambient air. As such, the perfusion loop may reduce the risk of infection, hemolysis and / or inflammation.

[0011] The perfusate may include filtered blood mixed with total parenteral nutrition and Steen solution at sub-normothermic temperature (approximately twenty-two deg. C). A dialysis machine may be used to remove the lactate and other metabolic wastes and may also maintain the balance of electrolytes in the perfusate circulated in the lung. By selecting, monitoring, and adjusting the perfusate, a lung may be preserved for longer durations, possibly longer than forty-eight hours.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] For a more detailed description of the embodiments of the disclosure, reference will now be made to the accompanying drawings, wherein:

[0013] FIG. 1 is a picture of an apparatus for supporting a lung during ex-vivo preservation that can be used to rotate the lung;

[0014] FIG. 2 is a picture of the apparatus shown in FIG. 1 illustrated after a lung laid in it and before the lung is encapsulated;

[0015] FIG. 3 is a picture of an airtight, expandable reservoir that can be used to a perfusate-and- ambient air interface; and

[0016] FIG. 4 is a schematic of a system for preserving a lung ex-vivo that includes the apparatus for supporting a lung shown in FIG. 1 and the airtight, expandable reservoir shown in FIG. 3.DETAILED DESCRIPTION

[0017] The preferred embodiment of an apparatus 10 for supporting a lung during ex-vivo preservation is illustrated in FIGs. 1 and 2. The apparatus 10 comprises a rotatory holder 12 (i.e., an example of receptacle), a flexible and tight-knit net 14 (i.e., an example of flexible and adherent membrane) designed to support the lung or lungs, and a rotatory mechanism 16 including a motor capable of automatically rotating the lung continuously or at defined intervals. The rotary holder 12 and the flexible and tight-knit net 14 are in a transparent chamber 18 (i.e., and example of case).

[0018] As shown in FIG. 2, the lung trachea is connected to a ventilator 20, so that the lung can be inflated and deflated by the active ventilation from the ventilator. The extent of lung inflations and deflations are controlled by the ventilator.

[0019] An inflow cannula 22 is inserted into the pulmonary artery, and the perfusate (filtered blood mixed with other nutrients) can flow into pulmonary artery and exit from the opened left atrium. The left atrium needs to be sealed and cannulated with no perfusate leaking into the chamber 18. For example, the left atrium of the lung is cannulated with a cuff 24.

[0020] In use, the flexible and tight-knit net 14, which is showed partially rolled in FIGs. 1 and 2, is unrolled. When the flexible and tight-knit net 14 is unrolled, it is sufficiently long to encapsulate the lung between an upper ply and a lower ply. Both, the lower ply and upper ply are secured to the rotary holder 12. Even when encapsulated, the lung is not prevented from inflating. If desired, the ventilator is held for a few seconds ('hold beath'), the lung is flipped, and then the ventilator resumes. The flexible and tight-knit net 14 prevents lung slip during rotation. Because of the friction between the flexible and tight-knit net 14 and the lung, the lung does not significantly move much while it is rotated.

[0021] As shown in FIG. 3, the cuff 24 is directly connected to bag 26 (an example of expandable reservoir) and the perfusate will be pumped back to the pulmonary artery, so that the circulating perfusate is not exposed to ambient air. Outside of the lung, the perfusate is circulated in an airtight loop that does not include any open-to-ambient air reservoir. The blood will then circulate back to the lung via the pulmonary artery cannula 22 (in FIG. 2).

[0022] As shown in FIG. 4, the apparatus 10, including the lung chamber 18 where the lung is laid in air, is combined with an ex vivo perfusion loop, including an expandable reservoir, an oxygenator, which is connected to a mixed gas tank, rotary blood pump; a heat exchanger (i.e., part of a heater and / or cooler); and several pressure and flow sensors. The mixed blood is collected in the expandable reservoir by gravity, and then circulated by a rotary blood pump, passed through an oxygenator (which served as a deoxygenator), and then flowed back into the pulmonary artery.

[0023] Preliminary studies to optimize the quality of circulating blood-based perfusate and temperature in the system were performed. Six pairs of porcine lungs were procured immediately after inducing cardiac arrest in the donors. Each was perfused and ventilated for up to 48 hours in the system. Heparinized porcine blood was filtered using a combination of leukocyte-reduced and microaggregate filters and adjusted to a target hematocrit of 17% using a low potassium dextran solution. Once the organ was instrumented onto system, blood flow was maintained at a target flow rate of 30% of the estimated cardiac output. Blood pH was monitored at level of 7.4 by either adding sodium bicarbonate or feeding a gas mixture of 10.5% CO2, 12% 02 and 77.5% N2 via the oxygenator. The lungs were ventilated with a PEEP of 5 mmHg, tidal volume of 6 mL / kg, and respiration rate of 10 breaths per minute. Four porcine lungs were preserved for up to 30 hours, including 2 porcine lungs past 48 hours.

[0024] In addition to the foregoing, the disclosure also contemplates at least the following embodiments 1-14. It should be noted that any element of any of embodiments 1-14 may further include details related to this element that are disclosed in a paragraph or figure describing the preferred embodiments without including details of other elements that are disclosed in the same or other paragraph or figure.Embodiment 1

[0025] Embodiment 1 is an apparatus for supporting a lung during ex -vivo preservation.

[0026] The apparatus comprises one or more membranes. For example, the one or more membranes may consist of one membrane that is folded. Alternatively, the one or moremembranes may consist of a plurality of membranes, each one of the plurality of membranes being separated from the other of the plurality of membranes, wherein each one of the plurality of membranes may or may not be folded.

[0027] The one or more membranes are sufficiently thin and are made of material (e.g., including silicone) that is sufficiently compliant so that the one or more membranes are flexible. As used herein, flexible means that the one or more membranes will bend under the weight of the lung resting on it or them. Preferably, the one or more membranes may also stretch under the weight of the lung resting on it or them.

[0028] The one or more membranes are adherent. As used herein, adherent means that the lung will not slip on the one or more membranes when the lung rests on it or them, and it or they are tilted by at least 45 deg., and preferably at least 60 deg., relative to the horizontal direction. The slippage is prevented at least partially by friction between the one or more membranes and the lung.

[0029] The apparatus comprises a receptacle for the one or more membranes. A receptacle is generally an open and rigid frame made for admitting, enclosing, or supporting the one or more membranes.

[0030] The apparatus comprises a framework. For example, the framework may rest on the floor, a table, etc. The receptacle is connected to the framework and rotatable relative to the framework, for example, using a handle or a motor.

[0031] The apparatus may be used to rotate the lung (e g., continuously rocked back and forth, flipped at particular times well separated by at least half an hour, one hour, four hours, etc., flipped at regular time intervals) to help blood circulation inside the lung, reduce damage, necrosis, and / or bruising of lung tissue.Embodiment 2

[0032] Embodiment 2 is an apparatus as described in embodiment 1, further comprising a case. The case is connected to the framework. The case encloses the receptacle and the one or more membranes.

[0033] The case may be used to maintain the lung at a sub-norm othermic temperature (e.g., at twenty-two deg. C + / - two deg. C).Embodiment 3

[0034] Embodiment 3 is an apparatus as described in embodiment 2, wherein the case includes at least one transparent window or panel.

[0035] The at least one transparent window or panel may be used for a professional to visually inspect the state of the lung during preservation.Embodiment 4

[0036] Embodiment 3 is an apparatus as described in any one of embodiments 1 to 3, wherein the one or more membranes form a capsule including a first layer suspended in an opening of the receptacle and a second layer suspended in the opening of the receptacle and overlaid over the first layer.

[0037] For example, a first ply of a folded membrane that may form the first layer and a second ply of the folded membrane that may form the second layer.

[0038] Alternatively, a first one of a plurality of membranes may form at least a portion of the first layer. A second one of the plurality of membranes may form at least a portion of the second layer.Embodiment 5

[0039] Embodiment 5 is an apparatus as described in any one of embodiments 1 to 4, wherein at least one of the one or more membranes is made of a stringy material, that is stitched so that the at least one of the one or more membranes forms a fabric having loops that are smaller than a diameter of the stringy material or, preferably, a net having loops that are larger than a diameter of the stringy material.

[0040] However, in other embodiments, the one or more membranes may be non-porous.Embodiment 6

[0041] Embodiment 6 is a system for preserving a lung ex-vivo.

[0042] The system comprises an apparatus for supporting a lung during ex-vivo preservation as described in any one of embodiments 1 to 5.

[0043] The system comprises a ventilator capable of being coupled to a trachea of the lung when the lung rests on at least one of the one or more membranes of the apparatus, and capable of inflating, and deflating the lung.

[0044] The system comprises a perfusion loop capable of injecting and withdrawing blood into an artery and a vein of the lung when the lung rests on at least one of the one or more membranes of the apparatus. The perfusion loop may or may not include a hemodialyzer.Embodiment 7

[0045] Embodiment 7 is a system as described in embodiment 6 wherein the perfusion loop comprises a hemodialyzer, a blood pump, and a deoxygenator coupled to a carbon dioxide tank.Embodiment 8

[0046] Embodiment 8 is a system as described in any of embodiments 6 or 7, wherein the perfusion loop comprises an airtight, expandable reservoir, wherein the airtight, expandable reservoir is placed lower than the one or more membranes of the apparatus so that the blood withdrawn from the lung can be collected in the airtight, expandable reservoir with assistance of gravity.

[0047] For example, the airtight, expandable reservoir may include a bag having at least two ports, which may or may not include a valve.Embodiment 9

[0048] Embodiment 9 is a system as described in any of embodiments 6 to 8, further comprising a heater, a cooler, or a combination of a heater and a cooler, capable of varying a temperature inside a case as described in any of embodiments 2 or 3.Embodiment 10

[0049] Embodiment 10 is a method of preserving a lung ex-vivo.

[0050] The method comprises the step of providing an apparatus for supporting a lung during ex-vivo preservation as described in any one of embodiments 1 to 5.

[0051] The method comprises the step of resting the lung on at least one of the one or more membranes of the apparatus.

[0052] The method comprises the step of rotating the lung to help blood circulation inside the lung, reduce damage, necrosis, and / or bruising of lung tissue.Embodiment 11

[0053] Embodiment 11 is a method of preserving a lung ex-vivo.

[0054] The method comprises the step of providing a system for preserving a lung ex-vivo as described in any one of embodiments 6 to 9.

Claims

[0055] The method comprises the step of resting the lung on at least one of the one or more membranes of the apparatus.[0056] The method comprises the step of rotating the lung to help blood circulation inside the lung, reduce damage, necrosis, and / or bruising of lung tissue.Embodiment 12[0057] Embodiment 12 is a method as described in any of embodiments 10 or 11, wherein rotating the lung comprises the step of flipping the lung at well separated, particular times.[0058] For example, the lung may be flipped at particular times separated by at least half an hour, one hour, four hours, etc. In particular, the lung may be slipped at regular time intervals. [0059] However, in other embodiments, the lung may be continuously rocked back and forth.Embodiment 13[0060] Embodiment 12 is a method as described in any of embodiments 11, wherein the perfusion loop comprises an airtight, expandable reservoir as described in embodiment 8.[0061] In use, the airtight, expandable reservoir is essentially devoid of air., whereby the risk of infection, hemolysis and / or inflammation is substantially reduced compared to exposure to ambient air.[0062] The method comprises the step of collecting blood withdrawn from the lung in the airtight, expandable reservoir with assistance of gravity.Embodiment 14[0063] Embodiment 12 is a method as described in embodiment 13, further comprising injecting a perfusate into an artery of the lung and withdrawing a perfusate from a vein of the lung, wherein the perfusate consists essentially of filtered blood mixed with total parenteral nutrition and Steen solution at a sub-normothermic temperature of (e.g., at twenty-two deg. C + / - two deg. C).[0064] Specific embodiments of the invention are shown by way of examples in the drawings and description. It should be understood, however, that the drawings and detailed description thereto are not intended to limit the invention to the particular form disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the disclosure.What is claimed is:

1. An apparatus for supporting a lung comprising: a rotatable receptacle; a flexible membrane supported by the receptacle and configured to support a lung; and a mechanism configured to move the rotatable receptacle.

2. The apparatus of claim 1, wherein at least a portion of the flexible membrane is adherent.

3. The apparatus of claim 1, wherein the flexible membrane comprises a tight-knit net.

4. The apparatus of claim 1, the rotatable receptacle comprises an open frame to which the flexible membrane is attached.

5. The apparatus of claim 1, further comprising a case that encloses the receptacle and the flexible membrane.

6. The apparatus of claim 1, wherein the flexible membrane forms a capsule that encloses the lung.

7. A system for preserving a lung comprising: a support apparatus including a rotatable receptacle supporting a flexible membrane configured to support a lung; a mechanism operable to move the rotatable receptacle; a ventilator configured to be coupled to a trachea of the lung; and a perfusion loop configured to be coupled to an artery or vein of the lung.

8. The system of claim 7 wherein the perfusion loop further comprises: a hemodialyzer; a blood pump coupled to the hemodialyzer; a deoxygenator coupled to the blood pump; and a carbon dioxide tank coupled to the deoxygenator.

9. The system of claim 7, wherein the perfusion loop further comprises an airtight, expandable reservoir configured to collect blood from the lung with the assistance of gravity.

10. The system of claim 7, further comprising a case that encloses the rotatable receptacle and the flexible membrane.

11. The system of claim 10, further comprising a temperature control system operable to control a temperature inside the case.

12. The system of claim 7, wherein at least a portion of the flexible membrane is adherent.

13. The system of claim 7, wherein the flexible membrane comprises a tight-knit net.

14. A method for preserving a lung comprising: supporting a lung in a flexible membrane that is coupled to a rotatable receptacle; coupling a trachea of the lung to a ventilator to selectively inflate and deflate the lung; coupling an artery or vein of the lung to a perfusion loop to circulate fluid through the lung; and selectively rotating the rotatable receptacle while controlling the inflation of the lung and circulation of fluid through the lung.

15. The method of claim 14, further enclosing the rotatable receptacle and the flexible membrane in a case coupled to a temperature control system.

16. The method of claim 14, further comprising controlling the temperature inside the case.

17. The method of claim 14, wherein at least a portion of the flexible membrane is adherent.

18. The method of claim 14, wherein the flexible membrane comprises a tight-knit net.

19. The method of claim 14, wherein the rotatable receptacle is continuously rotated.

20. The method of claim 14, wherein the rotatable receptacle is rotated at a specific time interval.

Images