Lung preservation in a liquid-filled, volume-changeable chamber

Abstract

A system for preserving a lung is close-to-air. Liquid can flow in and out of a ventilation chamber. Cannulations or other connections to the trachea, the left atrium, and the pulmonary artery of the lung are located at the bottom of the chamber. A lung is connected from the bottom of the chamber in an upside-down position, opposite direction as normal human anatomy. The lung floats in the liquid, approximately at the center of the chamber. A diaphragm or other movable plug located at the top of the chamber changes the lung volume. The chamber with the diaphragm can be discarded after use.

Description

LUNG PRESERVATION IN A LIQUID-FILLED,VOLUME-CHANGEABLE CHAMBERFIELD OF THE INVENTION

[0001] The application relates generally to a ventilation chamber for preserving a lung, a system for preserving a lung including the ventilation chamber, and a method for preserving a lung that utilizes the system. The application relates more particularly to a chamber, system and method for lung preservation in a close-to-air environment, such as involving a liquid- filled, volume-changeable chamber.BACKGROUND OF THE INVENTION

[0002] 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.

[0003] Current organ preservation techniques are short temi (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, rejected donor lungs can be evaluated and treated with drugs in an EVLP system.

[0004] However, there may still be shortcomings to EVLP systems. For example, the lung is preserved by active ventilation in an EVLP system, which in some cases could cause injury to the lungs, especially during long preservation. Due the lung weight, the lung has to be rotated every few hours in an EVLP system in order to reduce the risk of bruising on the side that directly contacts the support of the lung. The only way to control the temperature of the lung in an EVLP system is via the blood, and there is no control of the environment temperature. The lung is in an open-to-air environment in an EVLP system, which can bring risks of infection, risks of hemolysis, and gas exchange between the blood and the environment.

[0005] In view of the foregoing, there is a need for a chamber, system and method for lung preservation, preferably alleviating the pressure of the lung on its support that is caused by the lung weight.SUMMARY

[0006] 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.

[0007] In some aspects, the lung is generally preserved in a close-to-air environment. The benefit of a close-to-air environment over an open-to-air environment may include avoiding or reducing the escape of carbon dioxide in the environment, potentially leading to pH value increase in the lung tissue. The benefit of a close-to-air environment over an open-to-air environment may also include avoiding or reducing the chance of infection / contamination of the lung. More particularly, the lung may be preserved in liquid, such as saline mixed fluid, contained in a chamber. To eliminate the gravity pressure on the lung tissue, the lung may be floating in the chamber due to the buoyancy of the liquid.

[0008] In some aspects, a top portion of the chamber may include a piston, a diaphragm, or another equivalent form of movable plug. For example, the top portion of the chamber can include a rubber sheet; by moving the rubber sheet, the volume of the chamber will be changed. Because the chamber is filled by a liquid, which is nearly incompressible, the volume change causes air or other gas to be inhaled and exhaled by the lung. Inhalation is accompanied with a negative pressure in the chamber, and exhalation is accompanied with a positive pressure in the chamber. Because the piston, diaphragm, or other equivalent form of movable plug forms a top portion of the chamber, it does not need to hold or resist the weight of the liquid. Instead, the piston, diaphragm, or other equivalent form of movable plug can be driven with the force that is adequate to only change the lung volume. Also, if the chamber is implemented as a module in a system, the chamber including the piston, diaphragm, or other equivalent form of movable plug can be disconnected from the drive (e.g., an external linear actuator or equivalent motor), and be discarded or recycled after clinical use without having to discard or recycle the drive.

[0009] In some aspects, the lung trachea, and optionally, the lung blood vessels, are connected to the outside of the chamber from the bottom of the chamber so that the lung can be in an upside-downposition, in the opposite direction of the normal human anatomy. For example, the lung trachea, and optionally, the lung blood vessels (pulmonary vein and pulmonary artery), can be attached to a bottom disk that is part of a cap of the chamber. The trachea, and the blood vessels that are attached to the lungs are cannulated in order to anchor the lung in place inside of the chamber. The trachea cannula may pass through the bottom disk and may be open-to-air or to a gas tank, with or without an air-filter. The blood vessel cannulas may exit the chamber through the bottom disk and may be connectable to an ex-vivo loop for the lung perfusion. That is, the connection to the pulmonary artery cannulation in the lung and the connection to the pulmonary vein cannulation in the lung may pass through the bottom of the chamber. As such, the lung can be anchored to the bottom disk, thus floating in the center of the chamber without being compressed by the piston, diaphragm, or other equivalent form of movable plug. When the lung is held in this position, its condition may be easier to directly observe, and its inflation and deflation may be easier to control.

[0010] In some aspects, the chamber includes a transparent wall. The visibility of the lung in the chamber may allow the observation of the lung color, which can indicate if the lung is healthy. The visibility of the lung may also allow the observation of any leakage of blood, which can indicate the location of blood clots. The visibility of the lung may also allow the observation of the proper ventilation of all lobes of the lung.

[0011] In some aspects, the chamber is connected to a hydraulic circuit that contains the same liquid as in the chamber. Optionally, the hydraulic circuit can be configured to monitor and adjust the temperature of the liquid. For example, two connections for the liquid to flow in and out of the chamber can be provided through the bottom disk that is part of the cap of the chamber. Thus, the lung temperature may be more efficiently controlled than by altering the temperature of blood perfusate flowing in the lung.

[0012] In some aspects, the chamber and the hydraulic circuit are a part of a system for preserving the lung that comprises an ex-vivo loop for the lung perfusion, the ex-vivo loop including a dialysis machine. The dialysis machine can be used to remove the lactic acid and / or other waste from the blood perfusate and can also balance the electrolytes in the blood perfusate. For example, the blood perfusate can enter the lung via the pulmonary artery cannulation and leave the lung via the left atrium cannulation. The blood perfusate may then enter a hemodialyzer, be circulated by acentrifugal blood pump, pass through an oxygenator, and enter the lung back via the pulmonary artery cannulation.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] For a more detailed description of the embodiments of the disclosure, reference will now be made to the accompanying drawings, wherein:

[0014] FIG. 1 is a schematic of a system for preserving a lung according to a preferred embodiment;

[0015] FIG. 2 is a perspective view of a ventilation chamber shown in FIG. 1; and

[0016] FIG. 3 is a top view of a bottom disk shown in FIG. 2.DETAILED DESCRIPTION

[0017] A preferred embodiment of a system for preserving a lung is shown in FIG. 1. The lung 10 is floating inside a ventilation chamber 12 filled by a liquid 14, so there won't be tissue damage due to the lung lobes laying and pressing on a surface. The liquid temperature can also be adjusted by a heater / cooler 16 in this system, so the lung's temperature can be automatically controlled. In order to anchor the lung, a cannula for the trachea 18, a cannula 20 for the pulmonary artery and a cannula for the left atrium will be connected to the bottom disk 38 showed in FIG. 3, so the lung acts like a balloon held by the three cannulas and floating upside-down inside the chamber 12.

[0018] The inflow cannula 20 is inserted into the pulmonary artery 22, and a perfusate (e.g., filtered blood mixed with other nutrients) can flow into the pulmonary artery 22 and exit from the pulmonary vein or the opened left atrium 28. The perfusate is collected in a reservoir, and then circulated by a rotary blood pump 26, passes through an oxygenator 28 (which actually serves as a deoxygenator), and then flows back into the pulmonary artery 22.

[0019] Preliminary studies can be conducted to optimize the quality of the circulating blood-based perfusate and the temperature in a system for preserving a lung. For example, 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 for preserving a lung. 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 lung was instrumented, blood flow was maintained at a target flow rate of 30% of the estimated cardiac output. Blood pH wasmonitored and adjusted 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 tidal volume of 6 mL / kg, and respiration rate of 10 breaths per minute. Porcine lungs can be preserved for up to 30 hours, even past 48 hours.

[0020] Meanwhile, by changing the volume inside the ventilation chamber 12, the lung volume will be passively increased and decreased, leading to the lung 10 inhaling and exhaling air spontaneously. The trachea 18 is connected to air (ambient air or an air tank) via a cannula with or without an air filter. The ventilation chamber 12 is showed in FIG. 2. The chamber 12 includes a transparent wall 34, a bottom cap 36, and a bottom disk 38 that is part of the bottom cap 36. The chamber 12 is watertight, and its top side is fitted with the rubber sheet or piston 30 (i.e., a form of movable plug) that can move along the axial direction. The rubber sheet or piston 30 can be driven by an external motor 32 (in FIG. 1) that connects to it. The chamber 12 is filled with liquid 14 (e.g., saline or other type of liquids) that allows the lung 10 to float in. By precisely controlling the linear movement of the rubber sheet or piston 30 at the top end of the chamber motor, and keeping the liquid amount in the chamber 12 fixed, the size of the lung 10 resulting increases or decreases, resulting in passive ventilation of the lung 10. In other words, the increase in volume of the chamber 12 generates a negative pressure on the lung 10, pulling air into the lung 10 in a way similar to the way the human body breathes using the diaphragm.

[0021] The bottom disk 38 is illustrated in FIG. 3. The trachea 18 (in FIG. 1) is connected to ambient air via a cannula (e.g., a flexible tube extending from port 40). The pulmonary vein or left atrium 28 (in FIG. 1) of the lung will be sealed on a cannula (e.g., a flexible tube extending from port 42). The pulmonary artery 22 (in FIG. 1) of the lung will be sealed on a cannula (e.g., a flexible tube extending from port 44). As such, little to no blood is leaking into the chamber. Instead, the blood will be circulatory in a closed loop.

[0022] There may be several advantages to the system shown in FIGs. 1-3. There may not be bruise / edema on the lung due to the lung directly lying on the bottom surface of the chamber for a long period of time, since the lung is floating inside of the ventilation chamber. The temperature of the lung can be easily controlled by changing the liquid temperature in the ventilation chamber. Also, condensation due to the temperature difference between the system and the environment surrounding it is not an issue. The system is a close-to-air system, so it will less likely induceinfection, gas exchange between air and blood, and hemolysis. The lung is passively ventilated similar as in human body, instead of actively ventilation, thus reducing the risk of injury to the lung.

[0023] In addition to the foregoing, the disclosure also contemplates at least the following embodiments 1-15. It should be noted that any element of any of embodiments 1-15 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

[0024] Embodiment 1 is a ventilation chamber for preserving a lung.

[0025] The ventilation chamber comprises a wall having a top opening and a bottom opening. The wall is sized to surround a human lung. The wall is preferably transparent and rigid.

[0026] The ventilation chamber comprises a plug connected to the wall, wherein the plug is at least partially reciprocable relative to the wall and seals around the top opening of the wall;

[0027] The ventilation chamber comprises a cap connected to the wall, wherein the cap is rigid and seals around the bottom opening of the wall.

[0028] The ventilation chamber comprises a cannula extending through the cap, wherein the cannula is sized to be inserted into a trachea of the lung and to cause the lung to float upside-down in the chamber without being compressed by the plug; and

[0029] The ventilation chamber comprises a plurality of ports provided through the wall, the plug, or the cap.Embodiment 2

[0030] Embodiment 2 is a ventilation chamber as described in embodiment 1 wherein the wall comprises a cylinder having a bottom flange and a top flange.Embodiment 3

[0031] Embodiment 3 is a ventilation chamber as described in embodiments 1 or 2 wherein the plug comprises a flexible diaphragm.Embodiment 4

[0032] Embodiment 4 is a ventilation chamber as described in any embodiments 1 to 3 wherein the plurality of ports are provided through the cap.Embodiment 5

[0033] Embodiment 5 is a ventilation chamber as described in any embodiments 1 to 4 further comprising a hydraulic circuit coupled to two of the plurality of ports and capable of injecting and withdrawing liquid into the ventilation chamber around the lung.Embodiment 6

[0034] Embodiment 6 is a system for preserving a lung.

[0035] The system comprises a ventilation chamber as described in any of embodiments 1 to 5.

[0036] The system comprises a drive coupled to the plug and capable of at least partially reciprocating the plug relative to the wall so that a volume of the ventilation chamber can be increased and decreased.

[0037] The system comprises a perfusion loop coupled to another two of the plurality of ports and capable of injecting and withdrawing blood into an artery and a vein of the lung. The perfusion loop may or may not include a hemodialyzer.Embodiment 7

[0038] Embodiment 7 is a system as described in embodiment 6 wherein the drive comprises a linear actuator coupled to a support.Embodiment 8

[0039] Embodiment 8 is a system as described in embodiments 6 or 7 wherein the hydraulic circuit is capable of sealing a fixed volume of the liquid in the ventilation chamber and includes one of a heater and a cooler capable of varying a temperature of the liquid.Embodiment 9

[0040] Embodiment 9 is a system as described in any embodiments 6 to 8 wherein the perfusion loop comprises a hemodialyzer, a blood pump, and a deoxygenator coupled to a carbon dioxide tank.Embodiment 10

[0041] Embodiment 10 is a system as described in any embodiments 6 to 9 wherein the ventilation chamber and the hydraulic circuit form a module that can be connected to and disconnected from the drive.Embodiment 11

[0042] Embodiment 11 is a method for preserving a lung.

[0043] The method comprises the step of providing a ventilation chamber as described in any of embodiments 1 to 5.

[0044] The method comprises the steps of inserting the cannula into the trachea of the lung, and coupling a perfusion loop to two of the plurality of ports.

[0045] The method comprises the steps of coupling a hydraulic circuit to another two of the plurality of ports, flowing liquid into the ventilation chamber around the lung using the hydraulic circuit, and causing the lung to float upside-down in the liquid flown into the chamber without compressing the lung with the plug.

[0046] The method comprises the steps of injecting blood into an artery of the lung and withdrawing blood from a vein of the lung using the perfusion loop.

[0047] The method comprises the steps of sealing a fixed volume of the liquid in the ventilation chamber using the hydraulic circuit, coupling a drive to the plug, and reciprocating the plug relative to the wall at least partially so that a volume of the ventilation chamber is increased and decreased and air is inhaled and exhaled by the lung.

[0048] Preferably, the method is performed using the system described in any embodiments 6 to 10.Embodiment 12

[0049] Embodiment 12 is a method as described in embodiment 1 1 further comprising monitoring and adjusting a reciprocation of the plug relative to the wall.Embodiment 13

[0050] Embodiment 13 is a method as described in embodiments 11 or 12 further comprising monitoring and adjusting a temperature of the liquid.Embodiment 14

[0051] Embodiment 14 is a method as described in any embodiments 11 to 13 further comprising monitoring and adjusting a pH of the blood.Embodiment 15

[0052] Embodiment 15 is a method as described in any embodiments 11 to 14 wherein the liquid comprises a saline solution.

[0053] 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 claims.

Claims

What is claimed is:

1. A ventilation chamber for preserving a lung, comprising: a wall having a top opening and a bottom opening, wherein the wall is transparent, rigid, and sized to surround a lung; a plug connected to the wall, wherein the plug is at least partially reciprocable relative to the wall and seals around the top opening of the wall; a cap connected to the wall, wherein the cap is rigid and seals around the bottom opening of the wall; a cannula extending through the cap, wherein the cannula is sized to be inserted into a trachea of the lung and to cause the lung to float upside-down in the chamber without being compressed by the plug; and a plurality of ports provided through the wall, the plug, or the cap.

2. The ventilation chamber of claim 1 wherein the wall comprises a cylinder having a bottom flange and a top flange.

3. The ventilation chamber of claim 1 wherein the plug comprises a flexible diaphragm.

4. The ventilation chamber of claim 1 wherein the plurality of ports are provided through the cap.

5. The ventilation chamber of claim 1 further comprising a hydraulic circuit coupled to two of the plurality of ports and capable of injecting and withdrawing liquid into the ventilation chamber around the lung.

6. A system for preserving a lung, comprising: a ventilation chamber including: a wall having a top opening and a bottom opening, wherein the wall is transparent, rigid, and sized to surround a lung;a plug connected to the wall, wherein the plug is at least partially reciprocable relative to the wall and seals around the top opening of the wall; a cap connected to the wall, wherein the cap is rigid and seals around the bottom opening of the wall; a cannula extending through the cap, wherein the cannula is sized to be inserted into a trachea of the lung and to cause the lung to float upside-down in the chamber without being compressed by the plug; a plurality of ports provided through the wall, the plug, or the cap; and a hydraulic circuit coupled to two of the plurality of ports and capable of injecting and withdrawing liquid into the ventilation chamber around the lung; a drive coupled to the plug and capable of at least partially reciprocating the plug relative to the wall so that a volume of the ventilation chamber can be increased and decreased; and a perfusion loop coupled to another two of the plurality of ports and capable of injecting and withdrawing blood into an artery and a vein of the lung.

7. The system of claim 6 wherein the drive comprises a linear actuator coupled to a support.

8. The system of claim 6 wherein the hydraulic circuit is capable of sealing a fixed volume of the liquid and includes one of a heater and a cooler capable of varying a temperature of the liquid.

9. The system of claim 6 wherein the perfusion loop comprises a hemodialyzer, a blood pump, and a deoxygenator coupled to a carbon dioxide tank.

10. The system of claim 6 wherein the ventilation chamber and the hydraulic circuit form a module that can be connected to and disconnected from the drive.

11. A method for preserving a lung, comprising: providing a ventilation chamber including:a wall having a top opening and a bottom opening, wherein the wall is transparent, rigid, and sized to surround a lung; a plug connected to the wall, wherein the plug is at least partially reciprocable relative to the wall and seals around the top opening of the wall; a cap connected to the wall, wherein the cap is rigid and seals around the bottom opening of the wall; a cannula extending through the cap, wherein the cannula is sized to be inserted into a trachea of the lung and to cause the lung to float upside-down in the chamber without being compressed by the plug; and a plurality of ports provided through the wall, the plug, or the cap; inserting the cannula into the trachea of the lung; coupling a hydraulic circuit to two of the plurality of ports coupling a perfusion loop to another two of the plurality of ports; injecting liquid into the ventilation chamber around the lung using the hydraulic circuit; sealing a fixed volume of the liquid in the hydraulic circuit; causing the lung to float upside-down in the liquid injected in the chamber without compressing the lung with the plug; coupling a drive to the plug; injecting and withdrawing blood into an artery and a vein of the lung using the perfusion loop; and reciprocating the plug relative to the wall at least partially so that a volume of the ventilation chamber is increased and decreased, and air is inhaled and exhaled by the lung.

12. The method of claim 11 further comprising monitoring and adjusting a reciprocation of the plug relative to the wall.

13. The method of claim 11 further comprising monitoring and adjusting a temperature of the liquid.

14. The method of claim 11 further comprising monitoring and adjusting a pH of the blood.

15. The method of claim 11 wherein the liquid comprises a saline solution.

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