Patent Description:
The current invention generally relates to devices, systems, and methods for extracorporeal preservation of bodily tissue. Extracorporeal preservation of bodily tissue is essential in transplant procedures so that donor tissue can be transported to a recipient in a remote location. In order to provide the best graft survival rates, donor tissues must be matched to appropriate recipients. Because of the sudden nature of most tissue donation events, appropriate recipients must be rapidly located and must be within a limited geographic area of the donor. Time limitations on the extracorporeal viability of donor tissue can lead to less than ideal tissue matching and, worse, wasted donor tissue. Prolonging the viability of donor tissue can allow for better matching between donor tissue and recipients and, in turn, can increase graft survival rates and increase availability of donor tissue to the growing waitlists of individuals in need of transplants.

The most prevalent current technique for preserving a bodily tissue for transplantation is static cold storage. While hypothermic temperatures decrease the oxygen demand of the bodily tissue, the tissue's viability is still time-limited by insufficient oxygen levels to meet the tissue's decreased metabolic needs. Another known technique for preserving a bodily tissue for transplantation includes the use of hypothermic perfusion devices that can perfuse the tissue with oxygenated perfusate, supplying additional oxygen to the tissue's cells and prolonging tissue viability. The portability of such known devices is limited, however, because such known devices are large and require a significant volume of compressed gas and electrical power. Furthermore, such known devices are very complex, which can lead to increased manufacturing costs and higher failure rates.

An additional limitation of hypothermic storage is the tendency to cause edema, or the accumulation of fluid within the bodily tissue. The level of edema generally increases with the length of hypothermic storage, providing another limitation on the amount of time that a tissue can be stored and remain viable.

Because of the time limitations on tissue viability, even given modern hypothermic storage and perfusion techniques, tissue and organs are often transported via air and, accordingly, subjected to pressure changes associated with changes in altitude.

<CIT> describes a lung preservation device for lung transplantation. The device includes: a box, which is equipped with a trachea inlet, a lower temperature preservation solution inlet, a lower temperature preservation solution outlet, a box perfusate inlet and a box perfusate outlet, is internally provided with a lung stent, and is also equipped with a pressure regulation control valve that is connected to a pressure control source; a lung mantle, which is disposed in the box and provided with a vacuum pumping port, a lung inlet, a pulmonary artery perfusate inlet and a pulmonary vein perfusate outlet, wherein the pulmonary artery perfusate inlet is connected to the box perfusate inlet through a liquid inlet pipe, and the pulmonary vein perfusate outlet is connected to the box perfusate outlet through a liquid outlet pipe; a perfusate circulation system, which is arranged outside the box, has a liquid outlet connected to the box perfusate inlet, and has a liquid return port connected to the box perfusate outlet; and an oxygen supply device, which is arranged outside the box and is connected to a lung trachea.

<CIT> describes a box of lungs save set for lung transplant, the box is the transparent configuration, the box inner chamber forms lungs and holds the chamber, be provided with the trachea entry on the box, the liquid entry is preserved to low temperature, the liquid export is preserved to low temperature, perfusate entry and perfusate export, be provided with the lungs support in the box, still be provided with the pressure regulation control valve on the box, the pressure regulation control valve is connected with a pressure adjustment source, still be provided with temperature control system in the box, temperature control system is including setting up the temperature sensor in the box, heater and cooler. The document discloses can be through the atmospheric pressure condition in the pressure regulation control valve regulation box, transport or when highlands transportation or shipping, through the atmospheric pressure condition in the pressure regulation control valve change box when the needs long distance for the inside and outside pressure of box keeps the unanimity, avoids because the lung that the pressure differential caused harms the problem. Additionally, the document discloses can also realize the control and the change of temperature through temperature control system.

Systems and methods of the invention are directed to increasing donor tissue viability during and after storage and transport. In particular, systems and methods relate to storage and transport of lungs. As noted above, tissue transported by air may be subjected to changes in pressure associated with increases and decreases in altitude during flight. While changes in pressure may affect any tissue being transported, they can be particularly harmful to lung tissue. In typical donor lung retrieval and preparation, the donor lung is inflated with air and the trachea or bronchus is stapled to hold the air in the partially inflated lung and to keep preservation fluid out of the airways during storage and transport. Unfortunately, this inflation occurs on the ground and, once subjected to decreases in air pressure from flights at high altitude, the pressure differential between the sealed lung airways and surrounding preservation fluid and air can result in over inflation of the lung and damage to the tissue including rupturing of the alveoli or other air passages. Accordingly systems and methods of the invention may be used to monitor and maintain a relatively constant pressure within donor lungs during transport and storage while maintaining a desired level of inflation. Systems and methods can accomplish those tasks while maintaining separation between the non-sterile airway environment and the sterilized outer tissue surfaces and preservation fluid to help prevent infection of the donor tissue or the transplant recipient. Expandable accumulators of the invention may have variable volume and may include a gauge to indicate the volume of the accumulator. In certain embodiments, the accumulator may be filled to a volume based on the atmospheric pressure at the recovery site in order to compensate for various ambient pressures based on altitude or weather conditions in different locations. Methods may include adjusting the volume of the accumulator based on the ambient pressure at the recovery site before organ transport.

In accordance with the invention, an expandable accumulator is coupled to the airways of the donor lung(s) and sealed in fluid communication therewith. The expandable accumulator is more compliant than the airways of the donor lung such that the expandable accumulator expands in response to a relative increase in the volume of gas (e.g., through a change in relative pressure) contained in the closed system formed by the lungs airways and accumulator. By expanding, the accumulator can accommodate and absorb the relative increases in gas volume, stabilizing pressure within the system, and preventing over-inflation of and damage to the lung tissue.

Another drawback of current lung transport techniques is that lungs are typically transported horizontally on a flat surface or on a bed of crushed ice. Both techniques are far different from the geometry and orientation of the lung's anatomical home. By resting the lung horizontally, gravity can crush or damage the bottom-most airways. A rough bed of crushed ice only complicates the issue. Accordingly, systems and methods of the invention may include replicating the geometry of the chest cavity and/or the orientation of the lung therein during transport and storage of donor lungs. In certain embodiments, a lung or pair of lungs may be placed horizontally on a smooth surface with a raised central saddle portion to replicate the spine. Alternatively, a lung or pair of lungs may be suspended in an upright position similar to the orientation of the lung in a standing human body. In such instances, the lung or lungs may be suspended by the trachea or bronchus which may be secured to a support tube in fluid communication with, for example, an expandable accumulator as described above.

Systems and methods of the invention have application in both static cold storage devices and hypothermic machine perfusion devices. In certain embodiments, hypothermic machine perfusion devices are configured to oxygenate and perfuse a bodily tissue for extracorporeal preservation of the bodily tissue. In lung applications, the perfusate may be pumped through the lung's vasculature and kept separate from the closed airway-accumulator air system described above. The perfusion apparatuses can include a pneumatic system, a pumping chamber, and an organ chamber. The pneumatic system may be configured for the controlled delivery of fluid to and from the pumping chamber based on a predetermined control scheme. The predetermined control scheme can be, for example, a time-based control scheme or a pressure-based control scheme. The pumping chamber is configured to diffuse a gas into a perfusate and to generate a pulse wave for moving the perfusate through a bodily tissue. The organ chamber is configured to receive the bodily tissue and the perfusate. The organ chamber is configured to substantially automatically purge excess fluid from the organ chamber to the pumping chamber. The pumping chamber may be configured to substantially automatically purge excess fluid from the pumping chamber to an area external to the apparatus.

Devices, systems and methods are described herein that are configured for extracorporeal preservation and transportation of bodily tissue. Specifically, devices for monitoring and stabilizing pressure within inflated lungs are described. Systems and methods can compensate for pressure changes resulting from, for example, increases and decreases in altitude during air transport of the organ. By bleeding off and returning excess gases, volumetric expansion of the lung (i.e., over-inflation) may be prevented, avoiding damaging the organ which can result in decreased organ viability and decreased survival rates for transplant recipients. Additional aspects include contoured storage and transport chambers that can replicate the in-vivo anatomical orientation and geometry for a given organ. For example, a pair of donor lungs may be placed against a smooth, raised, central saddle designed to replicate the spine that the lungs would be resting against in vivo. Organs, such as lungs or hearts, may be suspended in an upright position to replicate the organ's orientation in a standing human and to prevent tissue damage caused by pressure from the organ's own weight resting on itself.

<FIG> illustrates a tissue preservation and transportation system <NUM> according to certain embodiments. An organ adapter <NUM> is adapted to be coupled to the airways (e.g., by the trachea or bronchus) of a lung <NUM>. The organ adapter <NUM> may comprise a lumen that, when the organ adapter <NUM> is coupled to the lung <NUM>, is in fluid communication with the airways of the lung <NUM>.

The organ adapter <NUM> is coupled to an expandable accumulator <NUM> and the lumen of the organ adapter <NUM> is in fluid communication with a sealed interior volume of the expandable accumulator <NUM>. The expandable accumulator <NUM> may be coupled by a valve <NUM>, to an inlet <NUM>. The inlet <NUM> has a lumen that, when the valve <NUM> is open, is in fluid communication with the interior volume of the expandable accumulator <NUM>, the lumen of the organ adapter <NUM>, and the airways of the lung <NUM>. When the valve <NUM> is closed, the interior volume of the expandable accumulator <NUM>, the lumen of the organ adaptor <NUM>, and the airways of the lung <NUM> form an air-tight, closed environment that is sealed from the outside environment including, for example, any preservation fluid present within the organ container <NUM>. The organ container <NUM> may include one or more boxes or bags configured to contain both the organ and any preservation fluid (e.g., temperature regulated, oxygenated fluid) in a sterilized environment. In preferred embodiments, the organ is placed into one or more sterile bags or boxes. For example, a lung may be placed in three concentric sterile bags fitted with a through-the-bag-wall cannula leading into the trachea plug. The cannula may include a filter for each bag (e.g., a <NUM>-micron sterile filter). Accordingly, both the exterior surface and interior, pressure-dampened lumen of the organ are surrounded by three sterile layers.

In various embodiments, the accumulator may have an interior volume (fully expanded) of about,. <NUM>, <NUM>, <NUM>,. <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or more liters. In preferred embodiments, the accumulator has a fully expanded interior volume of about <NUM> liter.

System <NUM> is configured to permit gas to move back and forth between the airways of the lung <NUM> through the lumen of the organ adapter <NUM>, and into the interior volume of the expandable accumulator <NUM>. When the valve <NUM> is open, the system <NUM> is configured to permit gas flow from the inlet <NUM>, through the valve <NUM>, into the lumen of the organ adaptor <NUM>, and finally into the airways of the lung <NUM>. The expansion resistance of the expandable accumulator <NUM> may be adjustable, fixed, or progressive.

The organ adapter <NUM> may be configured to substantially retain the bodily tissue (e.g., lung) with respect to the expandable accumulator <NUM>. The organ adapter <NUM> may be configured to permit movement of a gas from the expandable accumulator <NUM>, into the airways of the lung <NUM>, and back. The organ adapter <NUM> can be configured to be coupled to a bodily tissue such as a lung <NUM>. The organ adapter <NUM> can be coupled to the bodily tissue in any suitable manner. For example, in some embodiments, the organ adapter <NUM> can configured to be sutured to the bodily tissue. In another example, the organ adapter <NUM> is coupleable to the bodily tissue via an intervening structure, such as silastic or other tubing. In some embodiments, at least a portion of the organ adapter <NUM>, or the intervening structure, is configured to be inserted into the bodily tissue such as the lumen of a trachea, bronchus, or other air passage of a lung <NUM>. For example, in some embodiments, the lumen of the organ adapter <NUM> (or a lumen of the intervening structure) is configured to be fluidically coupled to a lumen of the bodily tissue such as an air passage of the lung <NUM>.

In various embodiments including the use of one or more sterile bags or other containers for the organ, the organ adapter may be contained in or integral to the inner most sterile bag and coupled to a through-the-bag-wall cannula that transverses each of the bags or other containers. The cannula, at the outer most bag or other container, may include an adapter to be removably coupled to the accumulator in the systems described herein. Accordingly, the bagged organ may be easily and quickly connected to the accumulator and inflated during loading and easily and quickly disconnected upon arrival at the transplantation site.

In some embodiments, the organ adapter (or simply referred as the adapter) can be configured to support the bodily tissue when the bodily tissue is coupled to the adapter. For example, in some embodiments, the adapter can include a retention mechanism (not shown) configured to be disposed about at least a portion of the bodily tissue and to help retain the bodily tissue with respect to the adapter. The retention mechanism can be, for example, a net, a cage, a sling, or the like. In some embodiments, the system can include a basket (not shown) or other support mechanism configured to support the bodily tissue when the bodily tissue is coupled to the adapter or otherwise received in the system. The organ adapter may be rigidly coupled to an interior wall (e.g. a lid) of an organ container such that the organ may be suspended via its connection point to the adapter.

The portion of the adapter that is inserted into a lumen of the organ may include a series of tapered steps such that a distal end of the adapter portion is narrower than a proximal end. In this manner, the adapter is configured to be inserted into a range of lumen sizes.

The lumen may be secured or sealed to the organ adapter via any means including elastic tension in the organ lumen itself or through the use of sutures, elastic band, or other securing mechanisms on the outside of the lumen applying pressure thereupon to form an air-tight seal between the lumen of the organ and the lumen of the adapter.

The expandable accumulator is configured to expand to accept relative increases in gas volume within the closed system in response to pressure differential changes between the closed system and the surrounding environment (e.g., during flight). The interior volume of the expandable accumulator should resist expansion with an opposing force that is less than that of the lung. Accordingly, decreases in internal pressure of the closed system due to decreases in the pressure of the surrounding environment (e.g. during flight) will be borne by the expandable accumulator such that the pressure within the system drops without volumetric expansion of the lung airways (which could cause tissue damage or rupture the airways).

The expandable accumulator is configured to be in constant communication with the internal (closed system) pressure and the external (surrounding environment) pressure, and to establish a nearly-constant differential between the two while having compliance higher than the lung's compliance. The pressure differential is such that the internal pressure is greater than the environment pressure. The pressure differential keeps the lungs inflated. The pressure differential would commonly be referred to as the gauge pressure. When the system is initially prepared, the external pressure may be <NUM> bar (absolute) and the internal pressure would be <NUM>+x bar, absolute (where the x is a suitable value chosen for best storage performance). The gauge pressure of the closed system is therefore x bar, and the differential pressure across the lung is also x bar. At a later time, in transport, the external pressure may be <NUM> bar for instance due to airplane cabin pressure when in flight. The internal pressure would be <NUM>+x bar, so the gauge pressure is again x bar, as is the pressure across the lung. In this manner the expandable accumulator maintains a nearly-constant pressure differential across the lung (from inside to outside).

In order to maintain the nearly-constant pressure differential the expandable accumulator will have a very high compliance, for example much higher than the lung compliance. In certain embodiments, the system may be configured to maintain about a <NUM> H<NUM>O gauge pressure inside the organ. The pressure may be fixed or may be tunable or adjustable using variable weight, spring tension, or other means depending on the accumulator mechanism. Pressure in the system may be set by filling the system to a desired fixed pressure or may be controlled using an adjustable accumulator which may be acted on by a computer based on inputs received from a pressure or other sensor as described below.

An inlet of the system may be used to add or remove a gas from the lumen of the organ (e.g., airways of a lung). For example, where donor lungs are at least partially inflated for storage and transport, a retrieved lung may be secured to an organ adapter as shown in <FIG>. The inlet may be then connected to a gas source such as a compressed air tank or a source of oxygen or another gas or combinations thereof. In certain embodiments, the gas source may comprise a pump or bulb for manually filling the system with ambient air or other gas. The pump or bulb may be integral to the transport container and travel with the container or may be used to establish pressure and removed after a valve located between the pump or bulb and the organ is closed. The valve connecting the inlet to the closed system of the lung airways, lumen of the adapter, and interior volume of the expandable accumulator may then be opened and oxygen or another gas or mixture of gasses may then be allowed to flow into the closed system. In certain embodiments (e.g., lung transport), gasses such as oxygen may damage the tissue and, as such, the fill gas will be selected accordingly (e.g., ambient air). The closed system may be inflated to a desired pressure which may be monitored with a pressure gauge or sensor located on the gas source or on the closed system. The pressure sensor may be electric and include a wireless sender located on the closed system such that pressure may be wirelessly monitored from outside an organ transport container during transport.

During inflation, as gas is admitted to the system, both the lungs and the expandable accumulator will inflate until reaching the desired gauge pressure (designated "x" above). As additional gas is thereafter admitted, the gas would preferentially fill the expandable accumulator given that component's higher compliance. When the expandable accumulator is entirely filled, the pressure would begin to rise above the "x" target, and the system would not have any remaining capacity. Therefore, when the system is filled the volume of gas may be adjusted such that a movable element of the expandable accumulator rests at a target position (for instance <NUM>% of travel). Once the expandable accumulator is at that target position, the valve can be closed and the closed system is sealed and ready for transport.

Once the lung has been inflated to a desired pressure, the valve may be closed, sealing off the closed system. The lung coupled to the expandable accumulator by the organ adapter along with the closed valve and the inlet may be then be placed in an organ container for storage or transport and may be at least partially submerged in a fluid such as a preservation fluid as known in the art. Examples of preservation fluid and static and perfusion-based tissue containers compatible with systems and methods of the invention are described in <CIT>.

The fill of the accumulator can be adjusted at organ recovery according to the local ambient (e.g. barometric) pressure. A smaller accumulator would thereby be able to work identically whether filled in Denver CO, or Boston MA, whatever the weather conditions. The accumulator may include a scale or other indicator in customary barometric pressure units. An exemplary pressure indicator <NUM> is shown in <FIG>, <FIG>, <FIG>, and <FIG>. An ambient pressure sensor or meter may also be included for reading ambient pressure at recovery. The system may then be filled until the piston reaches a mark on the scale or indicator on the accumulator that matches the local barometric pressure reading. If not adjusted to local pressure conditions, a larger accumulator may be used.

The expandable accumulator may be of any configuration that permits expansion of its interior volume with less resistance than that of the lung's airways. Examples of expandable accumulators are shown in <FIG>. Materials for transport and storage containers of the invention may be selected to reduce weight in key components such as the accumulator. For example, accumulators such as the rolling diaphragm types depicted in <FIG> and <FIG> may comprise a piston that slides within a cylinder to adjust volume to dampen pressure changes in the tissue. The piston or other accumulator components may be constructed of lightweight materials such as aluminum, plastics, or carbon fiber or may be constructed with lightweight techniques including low material thickness with structural bracing for example. Reducing the weight or mass of the moving pieces of the accumulator helps to minimize pressure changes resulting from movement (e.g., tilting) of the container or accumulator therein. Pressure generating force is thereby primarily established by an accumulator spring and relatively unaffected by gravity.

The expandable accumulator <NUM> depicted in <FIG> comprises a bellows-type interior bladder that permits expansion. The bellows may be contained within a shell that may be rigid to preserve an open interior volume into which the bellows can expand. The bellows may rely on inherent shape memory in the material of the bellows itself to provide resistance to expansion or may use, for example, springs opposing the expansion of the bellows via compression or tension. Any known spring type may be used including coiled materials or elastic bands to provide expansion resistance. The spring rate can be selected such that the expansion resistance provided to the interior volume of the accumulator is less than the expansion resistance of the lung's airways. The expansion resisting force may be a single rate or may be progressive or adjustable. The expansion resisting force can be modeled on the expansion resistance profile of lung airways in order to better maintain a constant pressure within the lung. In various embodiments, a constant force spring can be used to maintain internal pressure. Constant force springs are springs for which the force they exert over their range of motion is relatively constant. Constant force springs may be constructed from rolled ribbons of, for example, spring steel. In certain embodiments, the springs used in the systems depicted in <FIG> and <FIG> may be constant force springs. In some embodiments, a pair of constant force springs may be used in a back-to-back orientation.

<FIG> shows a system <NUM> including a lung <NUM>, an organ adapter <NUM>, an expandable accumulator <NUM>, a valve <NUM>, and an inlet <NUM> all placed within an organ container <NUM>. The components are configured and relate to each other in a similar manner to that shown in <FIG> aside from differences in the operation of the expandable accumulator <NUM>. The expandable accumulator <NUM> comprises a bellows type accumulator <NUM> that is not contained in a shell such that the outer surface of the expandable accumulator <NUM> is in direct communication with the interior environment of the organ container <NUM>. The expandable accumulator <NUM> may provide expansion resistance through its own material properties or through applied force from, for example, a spring.

<FIG> shows a system <NUM> including a lung <NUM>, an organ adapter <NUM>, an expandable accumulator <NUM>, a valve <NUM>, and an inlet <NUM> all placed within an organ container <NUM>. The components are configured and relate to each other in a similar manner to that shown in <FIG> aside from differences in the operation of the expandable accumulator <NUM>. The expandable accumulator <NUM> comprises a rolling diaphragm and a spring in compression to provide expansion resistance.

The rolling diaphragm contributes to a low-friction, low-hysteresis accumulator advantageous to tissue preservation as described herein, especially in lung preservation and transport apparatuses. The diaphragm may be constructed of any suitable material including latex, rubber, or silicon.

<FIG> shows a system <NUM> including a lung <NUM>, an organ adapter <NUM>, an expandable accumulator <NUM>, a valve <NUM>, and an inlet <NUM> all placed within an organ container <NUM>. The components are configured and relate to each other in a similar manner to that shown in <FIG> aside from differences in the operation of the expandable accumulator <NUM>. The expandable accumulator <NUM> comprises a rolling diaphragm and a spring in tension to provide expansion resistance.

A diaphragm-type accumulator system as exemplified in <FIG> and <FIG> may use a constant force spring to maintain a constant internal pressure in the lung or other organ. The diaphragm may be coupled to one or more springs in tension, compression, or some combination thereof (e.g., two opposing springs coupled to the diaphragm and providing expansion resistance through both compression and tension).

<FIG> shows a system <NUM> including a lung <NUM>, an organ adapter <NUM>, an expandable accumulator <NUM>, a valve <NUM>, and an inlet <NUM> all placed within an organ container <NUM>. The components are configured and relate to each other in a similar manner to that shown in <FIG> aside from differences in the operation of the expandable accumulator <NUM>. The expandable accumulator <NUM> comprises a balloon-type bladder wherein expansion resistance is provided by the elasticity of the material comprising the walls of the expandable accumulator <NUM>. As shown in <FIG>, the lungs <NUM> are suspended in a vertical orientation from the organ adapter <NUM> providing the benefits described above.

<FIG> shows a system <NUM> including a lung <NUM>, an organ adapter <NUM>, an expandable accumulator <NUM>, a valve <NUM>, and an inlet <NUM> all placed within an organ container <NUM>. The components are configured and relate to each other in a similar manner to that shown in <FIG> aside from differences in the operation of the expandable accumulator <NUM>. The expandable accumulator <NUM> depicted in <FIG> comprises a bellows-type interior bladder that permits expansion. The bellows may be contained within a shell that may be rigid to preserve an open interior volume into which the bellows can expand. The bellows may rely on inherent shape memory in the material of the bellows itself to provide resistance to expansion or may use, for example, gravity to provide the expansion resistance through a weight <NUM> placed on top of the bellows.

As noted, systems of the invention are compatible with and may include any static or perfusion-type preservation apparatus. An example of such a configuration is shown in <FIG>. An apparatus <NUM> is shown configured to oxygenate a perfusate (not shown) received in a pumping chamber <NUM> of the apparatus. The apparatus <NUM> includes a valve <NUM> configured to permit a fluid (e.g., oxygen) to be introduced into a first portion <NUM> of the pumping chamber <NUM>. A membrane <NUM> is disposed between the first portion <NUM> of the pumping chamber <NUM> and a second portion <NUM> of the pumping chamber. The membrane <NUM> is configured to permit the flow of a gas between the first portion <NUM> of the pumping chamber <NUM> and the second portion <NUM> of the pumping chamber through the membrane. The membrane <NUM> is configured to substantially prevent the flow of a liquid between the second portion <NUM> of the pumping chamber <NUM> and the first portion <NUM> of the pumping chamber through the membrane. In this manner, the membrane can be characterized as being semi-permeable.

The membrane <NUM> is disposed within the pumping chamber <NUM> along an axis A1 that is transverse to a horizontal axis A2. Said another way, the membrane <NUM> is inclined, for example, from a first side <NUM> to a second side <NUM> of the apparatus <NUM>. As such, as described in more detail below, a rising fluid in the second portion <NUM> of the pumping chamber <NUM> will be directed by the inclined membrane <NUM> towards a port <NUM> disposed at the highest portion of the pumping chamber <NUM>. The port <NUM> is configured to permit the fluid to flow from the pumping chamber <NUM> into the atmosphere external to the apparatus <NUM>. In some embodiments, the port <NUM> is configured for unidirectional flow, and thus is configured to prevent a fluid from being introduced into the pumping chamber <NUM> via the port (e.g., from a source external to the apparatus <NUM>). In some embodiments, the port <NUM> includes a luer lock.

The second portion <NUM> of the pumping chamber <NUM> is configured to receive a fluid. In some embodiments, for example, the second portion <NUM> of the pumping chamber <NUM> is configured to receive a liquid perfusate. The second portion <NUM> of the pumping chamber <NUM> is in fluid communication with an adapter <NUM>. The adapter <NUM> is configured to permit movement of the fluid from the pumping chamber <NUM> to a bodily tissue T. For example, in some embodiments, the pumping chamber <NUM> defines an aperture (not shown) configured to be in fluidic communication with a lumen (not shown) of the adapter <NUM>. The adapter <NUM> is configured to be coupled to the bodily tissue T. The adapter <NUM> can be coupled to the bodily tissue T in any suitable manner. For example, in some embodiments, the adapter <NUM> is configured to be sutured to the bodily tissue T. In another example, the adapter <NUM> is coupleable to the bodily tissue T via an intervening structure, such as silastic or other tubing. In some embodiments, at least a portion of the adapter <NUM>, or the intervening structure, is configured to be inserted into the bodily tissue T. For example, in some embodiments, the lumen of the adapter <NUM> (or a lumen of the intervening structure) is configured to be fluidically coupled to a vessel of the bodily tissue T.

Where the tissue T is, for example a lung, the airways of the tissue T may be coupled to an expandable accumulator <NUM> and associated systems as described herein via an organ adapter <NUM> (e.g., via the trachea or bronchus).

In some embodiments, the adapter <NUM> is configured to support the bodily tissue T when the bodily tissue T is coupled to the adapter. For example, in some embodiments, the adapter <NUM> includes a retention mechanism (not shown) configured to be disposed about at least a portion of the bodily tissue T and to help retain the bodily tissue T with respect to the adapter. The retention mechanism can be, for example, a net, a cage, a sling, or the like. In some embodiments, the apparatus <NUM> includes a basket (not shown) or other support mechanism configured to support the bodily tissue T when the bodily tissue T is coupled to the adapter <NUM> or otherwise received in the apparatus <NUM>.

An organ chamber <NUM> is configured to receive the bodily tissue T and a fluid. In some embodiments, the apparatus <NUM> includes a port <NUM> that is extended through the apparatus <NUM> (e.g., through the pumping chamber <NUM>) to the organ chamber <NUM>. The port <NUM> is configured to permit fluid (e.g., perfusate) to be introduced to the organ chamber <NUM>. In this manner, fluid can be introduced into the organ chamber <NUM> as desired by an operator of the apparatus. For example, in some embodiments, a desired amount of perfusate is introduced into the organ chamber <NUM> via the port <NUM>, such as before disposing the bodily tissue T in the organ chamber <NUM> and/or while the bodily tissue T is received in the organ chamber. In some embodiments, the port <NUM> is a unidirectional port, and thus is configured to prevent the flow of fluid from the organ chamber <NUM> to an area external to the organ chamber through the port. In some embodiments, the port <NUM> includes a luer lock. The organ chamber <NUM> may be of any suitable volume necessary for receiving the bodily tissue T and a requisite amount of fluid for maintaining viability of the bodily tissue T. In one embodiment, for example, the volume of the organ chamber <NUM> is approximately <NUM> liters.

The organ chamber <NUM> is formed by a canister <NUM> and a bottom portion <NUM> of the pumping chamber <NUM>. In a similar manner as described above with respect to the membrane <NUM>, an upper portion of the organ chamber (defined by the bottom portion <NUM> of the pumping chamber <NUM>) can be inclined from the first side <NUM> towards the second side <NUM> of the apparatus. In this manner, as described in more detail below, a rising fluid in the organ chamber <NUM> will be directed by the inclined upper portion of the organ chamber towards a valve <NUM> disposed at a highest portion of the organ chamber. The valve <NUM> is configured to permit a fluid to flow from the organ chamber <NUM> to the pumping chamber <NUM>. The valve <NUM> is configured to prevent flow of a fluid from the pumping chamber <NUM> to the organ chamber. The valve <NUM> can be any suitable valve for permitting unidirectional flow of the fluid, including, for example, a ball check valve.

The canister <NUM> can be constructed of any suitable material. In some embodiments, the canister <NUM> is constructed of a material that permits an operator of the apparatus <NUM> to view at least one of the bodily tissue T or the perfusate received in the organ chamber <NUM>. For example, in some embodiments, the canister <NUM> is substantially transparent. In another example, in some embodiments, the canister <NUM> is substantially translucent. The organ chamber <NUM> can be of any suitable shape and/or size. For example, in some embodiments, the organ chamber <NUM> can have a perimeter that is substantially oblong, oval, round, square, rectangular, cylindrical, or another suitable shape.

In use, the bodily tissue T is coupled to the adapter <NUM>. The pumping chamber <NUM> is coupled to the canister <NUM> such that the bodily tissue T is received in the organ chamber <NUM>. In some embodiments, the pumping chamber <NUM> and the canister <NUM> are coupled such that the organ chamber <NUM> is hermetically sealed. A desired amount of perfusate is introduced into the organ chamber <NUM> via the port <NUM>. The organ chamber <NUM> can be filled with the perfusate such that the perfusate volume rises to the highest portion of the organ chamber. The organ chamber <NUM> can be filled with an additional amount of perfusate such that the perfusate flows from the organ chamber <NUM> through the valve <NUM> into the second portion <NUM> of the pumping chamber <NUM>. The organ chamber <NUM> can continue to be filled with additional perfusate until all atmospheric gas that initially filled the second portion <NUM> of the pumping chamber <NUM> rises along the inclined membrane <NUM> and escapes through the port <NUM>. Because the gas will be expelled from the pumping chamber <NUM> via the port <NUM> before any excess perfusate is expelled (due to gas being lighter, and thus more easily expelled, than liquid), an operator of the apparatus <NUM> can determine that substantially all excess gas has been expelled from the pumping chamber when excess perfusate is released via the port. As such, the apparatus <NUM> can be characterized as self-purging. When perfusate begins to flow out of the port <NUM>, the apparatus <NUM> is in a "purged" state (i.e., all atmospheric gas initially within the organ chamber <NUM> and the second portion <NUM> of the pumping chamber <NUM> has been replaced by perfusate). When the purged state is reached, the operator can close both ports <NUM> and <NUM>, preparing the apparatus <NUM> for operation.

Oxygen (or another suitable fluid, e.g., gas) is introduced into the first portion <NUM> of the pumping chamber <NUM> via the valve <NUM>. A positive pressure generated by the introduction of oxygen into the pumping chamber <NUM> causes the oxygen to be diffused through the semi-permeable membrane <NUM> into the second portion <NUM> of the pumping chamber. Because oxygen is a gas, the oxygen expands to substantially fill the first portion <NUM> of the pumping chamber <NUM>. As such, substantially the entire surface area of the membrane <NUM> between the first portion <NUM> and the second portion <NUM> of the pumping chamber <NUM> is used to diffuse the oxygen. The oxygen is diffused through the membrane <NUM> into the perfusate received in the second portion <NUM> of the pumping chamber <NUM>, thereby oxygenating the perfusate.

In the presence of the positive pressure, the oxygenated perfusate is moved from the second portion <NUM> of the pumping chamber <NUM> into the bodily tissue T via the adapter <NUM>. For example, the positive pressure can cause the perfusate to move from the pumping chamber <NUM> through the lumen of the adapter <NUM> into the vessel of the bodily tissue T. The positive pressure is also configured to help move the perfusate through the bodily tissue T such that the bodily tissue T is perfused with oxygenated perfusate.

After the perfusate is perfused through the bodily tissue T, the perfusate is received in the organ chamber <NUM>. In this manner, the perfusate that has been perfused through the bodily tissue T is combined with perfusate previously disposed in the organ chamber <NUM>. In some embodiments, the volume of perfusate received from the bodily tissue T following perfusion combined with the volume of perfusate previously disposed in the organ chamber <NUM> exceeds a volume (e.g., a maximum fluid capacity) of the organ chamber <NUM>. A portion of the organ chamber <NUM> is flexible and expands to accept this excess volume. The valve <NUM> can then allow oxygen to vent from the first portion <NUM> of the pumping chamber <NUM>, thus, reducing the pressure in the pumping chamber <NUM>. As the pressure in the pumping chamber <NUM> drops, the flexible portion of the organ chamber <NUM> relaxes, and the excess perfusate is moved through the valve <NUM> into the pumping chamber <NUM>. The cycle of oxygenating perfusate and perfusing the bodily tissue T with the oxygenated perfusate can be repeated as desired.

<FIG> show an organ container <NUM> comprising a smooth raised portion <NUM> or saddle disposed on an interior wall of the organ container and designed to mimic the shape of the spine to replicate the in vivo environment of lungs being stored or transported. Such organ containers <NUM> are compatible with any other systems described herein including perfusing or static storage containers and various pressure regulating systems. <FIG> shows positioning of a pair of donor lungs <NUM> on a raised center portion <NUM> of an organ container <NUM> intended to mimic the spine in the lungs' in vivo environment.

The interior of organ containers of the invention may contain a fixed or removable shelf or tray configured to support cooling materials (e.g., frozen gel packs). Such a tray allows the organ to be loaded into the container before the tray is in place and, once the tray is inserted, the tray supports the cooling materials keeping them proximate to the organ for cooling purposes but prevents the materials from contacting the organ which can cause damage thereto. The tray may further serve to locate the organ within the colder bottom portion of the container.

<FIG> show an organ adapter <NUM> configured for insertion into the trachea of a donor lung to be transported using a tissue preservation and transportation system as described above. The organ adapter <NUM> may taper as shown in <FIG> to form an air-tight seal against the interior surface of the trachea or other organ opening to be transported and may include ridges <NUM> to aid retention of the adapter <NUM> within the organ opening once inserted. The organ adapter <NUM> includes tubing <NUM> for connecting to an expandable accumulator as described above and includes an inner lumen <NUM> for providing fluid communication between the accumulator and the interior of the organ. Once inserted into the organ, the organ adapter <NUM>, interior space of the organ, and the accumulator form a closed, air-tight system.

Systems of the invention may include a variety of sensors configured to sense and report, for example, temperature of the tissue, temperature of a preservation fluid or perfusate, pressure within the closed air system, pressure within the fluid, or ambient pressure. Displays for the sensors may be disposed on the outer surfaces of the organ transport or may be wirelessly linked to the internal sensors.

In some embodiments, a temperature sensor may include a probe positioned in the transport cavity and attached by a flexible cable to a temperature datalogger. The probe may not be wetted (i.e., the probe would remain outside of any sterile bags or containers) and may be suspended in air by a bracket or support in order to avoid direct contact with any cooling materials. The probe would thereby record and/or report the cavity temperature rather than the lung tissue temperature.

In certain embodiments, the sensor may comprise a mechanical flag that indicates the furthest expansion of the expandable accumulator and can therefore indicate if the accumulator reached maximum expansion presenting the possibility that additional pressure was absorbed by the lung tissue through over-inflation.

<FIG> shows an exemplary organ container <NUM> with an accumulator <NUM> having an accumulator scale <NUM> to indicate barometric pressure. As noted above, the indicator may be used by technicians when adjusting the accumulator to local pressure conditions. The organ container <NUM> may include a recess, port, or other feature for retaining the accumulator <NUM>, preferably, as shown in <FIG>, in a position that allows for external monitoring of the accumulator <NUM>. The organ container may include wheels and an extendable handle as shown for ease of transport and storage.

<FIG> shows an exploded view of an exemplary organ container <NUM>. The organ container <NUM> features an accumulator <NUM>, a gas source <NUM> (e.g., a bulb) for pressurizing the system, and an organ adapter <NUM> (e.g., a trachea plug) for interfacing an organ with the system. The organ container <NUM> also includes tubing <NUM> or connectors for coupling the gas source <NUM> and the organ adapter <NUM> to the accumulator <NUM>. The organ container <NUM> may also use a valve <NUM> (e.g., a roller clamp) operable to regulate fluid communication between the gas source <NUM> and the accumulator <NUM> by, for example, acting on the tubing <NUM>.

<FIG> shows a cross-sectional view of an exemplary organ container <NUM> illustrating an exemplary configuration of various components described herein including an accumulator <NUM> an organ adapter <NUM> (not coupled to an organ) and connecting tubing <NUM>. A sensor <NUM> (e.g., a temperature sensor) as described above, is also included at the bottom of the organ camber and, while potentially wireless in some embodiments, is depicted in <FIG> in a wired format in electronic communication with an external display <NUM> (e.g., an LCD screen) to display data obtained from the sensor <NUM>. An organ such as a lung would rest on the bottom of the cavity.

<FIG> shows an external view of an open organ container <NUM> with an accumulator <NUM> according to certain embodiments. With the lid removed from the exemplary organ container <NUM>, it is ready to accept or deliver an organ. The accumulator <NUM> with a pressure indicator <NUM> is shown placed in a fitted receptacle on the organ container <NUM>. A gas source <NUM> is connected by tubing <NUM> to the accumulator <NUM> and that connection is regulated by a valve <NUM>. The organ container <NUM> also features a storage pocket <NUM> for receiving and storing the gas source <NUM>, valve <NUM>, and tubing <NUM> when not in use. The illustrated organ container <NUM> does not have an organ loaded and so the organ adapter <NUM> inside the cavity is seen.

<FIG> shows an external view of an open organ container <NUM> with an accumulator <NUM> with pressure indicator <NUM>. A tray <NUM> is adapted to be positioned above a loaded organ in the cavity of the organ container <NUM> to hold cooling materials such as frozen gel packs off of the organ tissue surface. The tray may be supported by, for example, indentions in the interior walls of the cavity. The gas source <NUM> is shown stored in the storage pocket <NUM> for transport.

<FIG> shows a transverse cross-sectional view of an approximately empty accumulator <NUM> according to certain embodiments and <FIG> shows a lateral cross-sectional view. The accumulator <NUM> includes a piston <NUM> and a rolling diaphragm <NUM> as described above. As seen in <FIG>, a pair of back-to-back constant force springs <NUM> comprising rolled ribbons of, for example, spring steel.

<FIG> shows a lateral cross-sectional view of an approximately half full accumulator <NUM> and <FIG> shows a lateral cross-sectional view of an approximately full accumulator <NUM>. As seen in <FIG>, as the accumulator <NUM> is filled or expands, the rolling diaphragm <NUM> unfolds while the ribbons of the constant force springs <NUM> unwind thereby providing resistance against said expansion. As noted earlier, the rolling diaphragm <NUM> helps maintain a seal between the outer surface of the piston <NUM> and the inner wall of the accumulator <NUM> while minimizing friction between the two surfaces that might interfere with the expansion or operation of the accumulator <NUM>.

<FIG> shows an exploded view of an accumulator <NUM>. The outer barrel of the accumulator <NUM> may be constructed of a material such as polycarbonate plastic and is preferably transparent enough for the position of the piston <NUM> therein to be externally readable against a pressure indicator <NUM> on the accumulator <NUM>. For example, the top edge of the piston <NUM> may align with a mark on the pressure indicator <NUM> to indicate a pressure setting. A clear outer barrel may also allow for monitoring of the state of the piston <NUM> within the accumulator <NUM> during transport to observe, for example, a maximum displacement thereof. <FIG> shows a pair of constant force springs <NUM> and a pair of connectors <NUM> configured to couple to tubing to provide fluid communication between the interior of the accumulator <NUM> and a gas source and an organ via an organ adapter.

As one skilled in the art would recognize as necessary or best-suited for the systems and methods of the invention, systems and methods of the invention may include computers that may include one or more of processor (e.g., a central processing unit (CPU), a graphics processing unit (GPU), etc.), computer-readable storage device (e.g., main memory, static memory, etc.), or combinations thereof which communicate with each other via a bus. Computers may include mobile devices (e.g., cell phones), personal computers, and server computers. In various embodiments, computers may be configured to communicate with one another via a network in order to display image series or allow remote storage, viewing, or selection of images of a given series.

A processor may include any suitable processor known in the art, such as the processor sold under the trademark XEON E7 by Intel (Santa Clara, CA) or the processor sold under the trademark OPTERON <NUM> by AMD (Sunnyvale, CA).

Memory preferably includes at least one tangible, non-transitory medium capable of storing: one or more sets of instructions executable to cause the system to perform functions described herein (e.g., software embodying any methodology or function found herein); data (e.g., portions of the tangible medium newly re-arranged to represent real world physical objects of interest accessible as, for example, a picture of an object like a motorcycle); or both. While the computer-readable storage device can in an exemplary embodiment be a single medium, the term "computer-readable storage device" should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the instructions or data. The term "computer-readable storage device" shall accordingly be taken to include, without limit, solid-state memories (e.g., subscriber identity module (SIM) card, secure digital card (SD card), micro SD card, or solid-state drive (SSD)), optical and magnetic media, hard drives, disk drives, and any other tangible storage media.

Input/output devices according to the invention may include one or more of a video display unit (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT) monitor), an alphanumeric input device (e.g., a keyboard), any temperature, pressure, or other sensor described herein, a cursor control device (e.g., a mouse or trackpad), a disk drive unit, a signal generation device (e.g., a speaker), a touchscreen, a button, an accelerometer, a microphone, a cellular radio frequency antenna, a network interface device, which can be, for example, a network interface card (NIC), Wi-Fi card, or cellular modem, or any combination thereof.

One of skill in the art will recognize that any suitable development environment or programming language may be employed to allow the operability described herein for various systems and methods of the invention. For example, systems and methods herein can be implemented using Perl, Python, C++, C#, Java, JavaScript, Visual Basic, Ruby on Rails, Groovy and Grails, or any other suitable tool. For a computer, it may be preferred to use native xCode or Android Java.

Lung volume and pressure conditions were modeled during transport without an accumulator, with a spring-based accumulator, and with a weight based accumulator (as described above). Since PV = nRT (ideal gas law) the trapped volume inside the lung will obey pV/T = constant or pf Vf / Tf = po Vo / To where "o" refers to starting and "f" to final conditions.

P is the atmospheric pressure, absolute, p is the internal pressure, absolute, biased somewhat above P. V is the contained volume (lung, tubing, accumulator) T is the temperature in Kelvin.

For pressure the model defines and uses cmH<NUM><NUM> and atm (the SI unit standard). Pressure measurements are absolute unless otherwise stated.

Ambient Pressure (P) can range between the following (note that weather measurements are usually in inHg): <MAT>.

Altitude at recovery should be accounted for. For example, the typical pressure in a city such as Denver, Colorado may be calculated as: <MAT>.

The range of Po is from ~<NUM> to ~<NUM> atm. Lung temperature (T) can range between the following (assumes that recovery occurs in cold operating rooms and transport is under not as cold conditions): <MAT>.

To model transit conditions, it is assumed that T stays approximately constant. Allowing Tf to rise to <NUM> is conservative. Extremes of pressure will be seen in airplane cabins and is approximated as follows for various aircraft (Cabin Pressure is typically measured in equivalent altitude): <MAT> <MAT> <MAT> <MAT>.

So flight pressures can range from <NUM> up to <NUM> atm.

Range Values for Exploring Solution Space:
i := <NUM>. <NUM> (where i is the ambient pressure index); j := <NUM>. <NUM> (where j is the initial conditions index for solutions of multiple cases simultaneously); Pmin := <NUM> atm and Pmax := <NUM> atm <MAT>.

The lung values used herein are taken from literature. The volumes at <NUM> cmH<NUM>O and above are extrapolated. The resulting interpolated lung pressure-volume model is large: volume is <NUM> liters at 15cmH2O. The pressure-volume model was scaled to establish a resting volume of <NUM> at 15cmH2O.

The scaled, max-limited Lung Volume formula is then: <MAT> (where p = internal and P = external pressure, absolute).

A graph of the lung curve can be modeled using the following equation: <MAT> <MAT>.

A graph of the target volume, pressure and target compliance can be created as follows: <MAT>.

The curve of an ex-vivo lung model, volume vs. pressure is shown in <FIG>. The target shown is a lung volume of <NUM> at 15cmH2O. The curve is taken from literature and scaled (on Yaxis) to pass through target. Values for pressure > <NUM> cmH2O are extrapolated.

Accumulator parameters for the model were varied based on the accumulator used as follows:.

<MAT> atm where Po is the external environmental pressure.

The accumulator's behavior was used to determine po and Vo, e.g., the initial internal pressure volume at the above Po and To given all other parameters. The accumulator is filled to the target volume, which sets the internal pressure.

The lung volume was determined by the initial and external pressures as: <MAT>.

The Contained Volume Vo is the sum of accumulator and lung volumes. This is the initial volume of air inside the system. This mass of air will remain unchanged, so the ideal gas law governs its subsequent behavior (relationship of pressure to volume). Vo can be defined as follows for the various accumulator types:.

The equation for final volume Vf is based on the ideal gas law for contained volume, <MAT> solved for Vf: <MAT>.

The adapted equation was used in the solve function below: <MAT> given: <MAT> with the following constraint added: <MAT> providing a solution of: <MAT>.

The inputs to this function are the initial conditions together with travel pressure and temperature. The output of this function is the internal pressure.

The solution for a defined range of conditions can then be found: <MAT> <MAT> <MAT> <MAT>.

<FIG> and <FIG> show lung pressure and volume in no-accumulator systems given various parameters. Lung pressure and volume were plotted in <FIG> given the following:.

Given the above values, <FIG> shows lung pressure and volume across a range of ambient (atmospheric) pressures during transit without an accumulator based on three different atmospheric pressures at recovery (<NUM> atm, <NUM> atm, and <NUM> atm). Lung volume, recovery at <NUM> Patm <NUM>, lung volume, recovery at <NUM> Patm <NUM>, lung volume, recovery at <NUM> Patm <NUM>, and accumulator volume <NUM> (set to zero here to represent a lack of accumulator) are plotted against the left hand scale. Lung pressure, recovery at <NUM> Patm <NUM>, lung pressure recovery at <NUM> Patm <NUM>, and lung pressure, recovery at <NUM> Patm <NUM> are plotted against the right hand scale.

<FIG> shows lung pressure and volume across a range of ambient (atmospheric) pressures during transit without an accumulator with recovery at <NUM> atm. The values are the same as given for the nominal (<NUM> atm recovery pressure) plot in <FIG>.

As shown in <FIG> and <FIG>, the lung volume and pressure vary markedly in response to changes in the in-transit ambient pressure from airplane ascent and descent. These changes can cause damage to the lung tissue and negatively impact viability of the organ for transplant.

<FIG> and <FIG> show lung pressure and volume in spring-based accumulator systems given various parameters. Lung pressure and volume were plotted in <FIG> given the following:.

Given the above values, <FIG> shows lung pressure and volume across a range of ambient (atmospheric) pressures during transit with a spring-based accumulator based on three different atmospheric pressures at recovery (<NUM> atm, <NUM> atm, and <NUM> atm). Lung volume, recovery at <NUM> atm, <NUM> atm, and <NUM> atm <NUM> and accumulator volume <NUM> are plotted against the left hand scale. Lung pressure, recovery at <NUM> atm, <NUM> atm, and <NUM> atm <NUM> are plotted against the right hand scale. Of note compared to <FIG>, the lung volume, lung pressure, and accumulator volume curves are consistent across the various atmospheric pressure conditions at recovery because the accumulator volume set at the time of recover compensates for these differences. Furthermore, as shown in <FIG>, the lung volume and lung pressure curves are much flatter than those in <FIG> and <FIG> (without an accumulator) while the accumulator volume changes to offset pressure differentials caused by changes in cabin pressure.

<FIG> and <FIG> show lung pressure and volume in weight-based accumulator systems given various parameters. Lung pressure and volume were plotted in <FIG> given the following:.

Given the above values, <FIG> shows lung pressure and volume across a range of ambient (atmospheric) pressures during transit with a weight-based accumulator based on three different atmospheric pressures at recovery (<NUM> atm, <NUM> atm, and <NUM> atm). Lung volume, recovery at <NUM> atm, <NUM> atm, and <NUM> atm <NUM> and accumulator volume <NUM> are plotted against the left hand scale. Lung pressure, recovery at <NUM> atm, <NUM> atm, and <NUM> atm <NUM> are plotted against the right hand scale. As with <FIG>, the lung volume, lung pressure, and accumulator volume curves are consistent across the various atmospheric pressure conditions at recovery because the accumulator volume, set at the time of recover compensates for these differences. The lung volume and pressure curves are slightly flatter than the spring-based accumulator curves in <FIG>.

Claim 1:
A system (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) for storage of one or more lungs (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>), the system (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) comprising:
an expandable accumulator (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) comprising an expandable inner volume; and
an organ adapter (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) comprising a lumen in fluid communication with the expandable inner volume and configured to be coupled to a lumen of the one or more lungs (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) to form a closed air system between the expandable inner volume and the lumen of the one or more lungs (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>),
wherein the expandable accumulator (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) has an expansion resistance that is adjustable such as to provide an expansion resistance that is less than the expansion resistance of the lumen of the one or more lungs (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>), and
wherein the expandable accumulator (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>), organ adaptor (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>), and the one or more lungs (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) are configured to be all contained within an organ container (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>).