JP2023088347A - Organ preservation device and organ preservation method - Google Patents

Abstract

To provide a technique for appropriately adjusting carbon dioxide partial pressure and pH of a perfusion liquid without using a complex control mechanism.SOLUTION: An organ preservation device 1 comprises: a liquid storage unit 30; pipings 41, 51, and 61 for circulating a liquid between the liquid storage unit 30 and an organ 9; a gas exchange unit 70; and a pH measurement unit 80. The gas exchange unit 70 includes a first valve 723 provided in an air supply pipe 721 for connecting a gas supply source 722 and a gas phase of a gas exchange module 71, and a second valve 732 provided in an exhaust pipe 731 for discharging gas from the gas phase of the gas exchange module 71. A control unit 10 controls the first and second valves 723 and 732 on the basis of a measurement value of the pH measurement unit 80.SELECTED DRAWING: Figure 1

Description

The present invention relates to an organ preservation device and an organ preservation method for preserving organs outside the body.

In organ transplantation surgery such as liver transplantation, the organ is temporarily preserved outside the body after the organ is removed from the donor until the organ is transplanted to the recipient. At this time, in order to prevent the organ from being in an ischemic state, the organ may be housed in a storage container and a perfusion treatment of perfusing the organ with a storage solution may be performed. A perfusion apparatus for perfusing an organ outside the body is described in Patent Document 1, for example.

Japanese Patent Publication No. 2017-518301

Due to the worldwide shortage of donor organs in current organ transplantation medicine, there is a demand for the development of an organ perfusion system that more closely reproduces the in vivo blood circulation in order to restore the function of donor organs. Perfusion treatment for the purpose of functional recovery provides a regular supply of oxygen and nutrients that are generally consumed by the metabolism of the organ. However, conventional perfusion devices do not take countermeasures against carbon dioxide (CO ₂ ) calculated by organ metabolism.

Carbon dioxide excreted from the organ is converted to bicarbonate ions in the perfusate, lowering the pH of the perfusate. As a result, the pH of the perfusate may deviate from the normal pH range (for example, pH 7.36 to 7.44) that does not burden the organs.

The present invention has been made in view of such circumstances, and provides a technique for appropriately adjusting the carbon dioxide partial pressure and pH of the perfusate without using a complicated control mechanism in organ perfusion treatment. With the goal.

In order to solve the above-mentioned problems, a first invention of the present application is an organ preservation apparatus for preserving an organ while perfusing the organ with a liquid outside the body, comprising a liquid reservoir for storing the liquid, and the liquid reservoir. and the organ, a pH measuring unit inserted in the pipe, a gas exchange unit performing gas exchange with respect to the liquid flowing in the pipe, and a control unit. the gas exchange unit includes a liquid phase through which the liquid in the pipe passes, a gas phase through which gas passes, and a gas exchange membrane that performs gas exchange between the liquid phase and the gas phase; A gas supply source that supplies a gas containing oxygen to the gas phase, a first valve provided in an air supply pipe that connects the gas supply source and the gas phase, and a first valve provided in an exhaust pipe that discharges gas from the gas phase and a second valve, wherein the control unit controls the first valve and the second valve based on the measured value of the pH measurement unit.

A second invention of the present application is the organ preservation apparatus according to the first invention, wherein the control unit opens the second valve, and when the pH value measured by the pH measurement unit decreases, the first When the opening degree of the valve is increased and the pH value measured by the pH measuring unit increases, the opening degree of the first valve is decreased.

A third invention of the present application is the organ preservation apparatus according to the first invention, wherein the control unit opens the first valve, and when the pH value measured by the pH measurement unit decreases, the second When the opening degree of the valve is increased and the pH value measured by the pH measuring unit increases, the opening degree of the second valve is decreased.

A fourth invention of the present application is an organ preservation method for preserving an organ while perfusing the organ with a liquid outside the body, wherein the liquid is stored between a liquid reservoir in which the liquid is stored and the organ via a pipe. A gas exchange unit is inserted in the pipe, and the gas exchange unit includes a liquid phase through which the liquid in the pipe passes, a gas phase through which the gas passes, and the A gas exchange membrane that performs gas exchange between a liquid phase and the gas phase, a gas supply source that supplies a gas containing oxygen to the gas phase, and an intake pipe that connects the gas supply source and the gas phase. and a second valve provided in an exhaust pipe for exhausting gas from the gas phase, wherein during the perfusion step: a) measuring the pH of the liquid in the pipe; and b) controlling the first valve and the second valve based on the measured values in step a).

The fifth invention of the present application is the organ preservation method of the fourth invention, wherein in the perfusion step, the second valve is opened, and in the step b), the pH value measured in the step a) is When the pH becomes smaller, the degree of opening of the first valve is increased, and when the value of pH measured in step a) becomes greater, the degree of opening of the first valve is decreased.

The sixth invention of the present application is the organ preservation method of the fourth invention, wherein in the perfusion step, the first valve is opened, and in the step b), the pH value measured in the step a) is When the pH becomes smaller, the degree of opening of the second valve is increased, and when the value of pH measured in step a) increases, the degree of opening of the second valve is decreased.

According to the first to sixth inventions of the present application, it is possible to appropriately adjust the carbon dioxide partial pressure and pH of the perfusate without using a complicated control mechanism in organ perfusion treatment.

In particular, according to the second and fifth inventions of the present application, the carbon dioxide partial pressure and pH of the perfusate can be appropriately adjusted by adjusting the opening of the first valve.

In particular, according to the third and sixth inventions of the present application, by adjusting the degree of opening of the second valve, the carbon dioxide partial pressure and pH of the perfusate can be appropriately adjusted.

It is the figure which showed the structure of the organ preservation|save apparatus which concerns on 1st Embodiment. FIG. 4 is a diagram schematically showing the internal structure of the gas exchange module; 4 is a flowchart showing the flow of perfusion processing; 4 is a flow chart showing the flow of an opening degree determination step in pH adjustment processing. It is the figure which showed the structure of the organ preservation apparatus which concerns on 2nd Embodiment. FIG. 10 is a diagram showing the results of Experiment 1; FIG. 10 is a diagram showing the results of Experiment 2;

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described with reference to the drawings.

As used herein, "donors" and "recipients" may be human or non-human animals. That is, in the present application, an "organ" may be either a human organ or a non-human animal organ. Non-human animals may also be rodents, including mice and rats; ungulates, including pigs, goats, and sheep; non-human primates, including chimpanzees; Animals other than animals may be used.

<1. First Embodiment>
<1-1. Configuration of Organ Preservation Apparatus>
FIG. 1 is a diagram showing the configuration of an organ preservation apparatus 1 according to the first embodiment. This organ preservation apparatus 1 is an apparatus for temporarily preserving an organ 9 removed from a donor outside the body during an organ transplant operation until the organ is transplanted to a recipient. Below, the case where the preserved organ 9 is the liver will be described.

Examples of the organ 9 preserved in the organ preservation apparatus 1 include a kidney, a heart, and a pancreas in addition to the liver. However, the organ 9 preserved in the organ preservation apparatus 1 may be another organ or a part of the organ. The organ preservation apparatus 1 preserves the organ while perfusing the blood vessels in the organ 9 with a liquid such as physiological saline, UW solution, and ETK solution (hereinafter collectively referred to as "perfusate").

As shown in FIG. 1, the organ preservation apparatus 1 of this embodiment includes an organ container 20, a liquid storage section 30, a first liquid supply section 40, a second liquid supply section 50, a liquid recovery section 60, and a gas exchange section 70. , a pH measurement unit 80 and a control unit 10 .

The organ container 20 is a container that houses an organ extracted from a donor. The organ container 20 is, for example, a cylindrical (cup-shaped) container with a bottom. In addition, the organ container 20 may have a lid that covers the opening in order to prevent the surface of the internal organ from drying out. The organ container 20 is made of resin, for example.

The liquid storage part 30 is a main tank in which the perfusate is stored. The first liquid supply section 40 and the second liquid supply section 50 supply perfusate from the liquid storage section 30 to the organ 9 . In this embodiment, since the organ 9 is the liver, two liquid supply units 40 and 50 are used to supply perfusate to two blood vessels, the portal vein and the hepatic artery. It should be noted that when the perfusate is supplied to only one blood vessel of the organ 9, only one of the first liquid supply section 40 and the second liquid supply section 50 may be used.

The first liquid supply section 40 has a first liquid supply pipe 41 , a first pump 42 and a first air trap 43 . The upstream end of the first liquid supply pipe 41 is connected to the liquid reservoir 30 . A downstream end of the first liquid supply pipe 41 is connected to a blood vessel of the organ 9 . In the present embodiment, the downstream end of the first liquid supply pipe 41 is connected to the portal vein of the liver, which is the organ 9 .

The first pump 42 and the first air trap 43 are interposed in the first liquid supply pipe 41 . The first pump 42 causes a flow from the upstream side to the downstream side inside the first liquid supply pipe 41 . As a result, the perfusate is supplied from the fluid reservoir 30 to the portal vein of the liver, which is the organ 9 , through the first fluid supply pipe 41 . A centrifugal pump, for example, is used for the first pump 42 . The first air trap 43 is arranged downstream of the first pump 42 . In the first air trap 43, air bubbles generated by separation of gas dissolved in the perfusate flowing in the first liquid supply pipe 41 are removed from the perfusate.

The second liquid supply section 50 has a second liquid supply pipe 51 , a second pump 52 and a second air trap 53 . The upstream end of the second liquid supply pipe 51 is connected to the liquid reservoir 30 . A downstream end of the second liquid supply pipe 51 is connected to a blood vessel of the organ 9 . In this embodiment, the downstream end of the second liquid supply pipe 51 is connected to the hepatic artery of the liver, which is the organ 9 .

A second pump 52 and a second air trap 53 are interposed in the second liquid supply pipe 51 . The second pump 52 causes a flow from the upstream side to the downstream side inside the second liquid supply pipe 51 . As a result, the perfusate is supplied from the liquid reservoir 30 through the second liquid supply pipe 51 to the hepatic artery of the liver, which is the organ 9 . A centrifugal pump, for example, is used for the second pump 52 . A second air trap 53 is arranged downstream of the second pump 52 . In the second air trap 53, air bubbles generated by separation of gas dissolved in the perfusate flowing in the second liquid supply pipe 51 are removed from the perfusate.

The liquid recovery unit 60 recovers the perfusate discharged from the organ 9 and returns it to the liquid storage unit 30 . The liquid recovery section 60 has a recovery pipe 61 , a recovery tank 62 and a recovery pump 63 . The liquid supply pipes 41 and 51 and the recovery pipe 61 constitute a “pipe” for circulating the perfusate (liquid) between the liquid reservoir 30 and the organ 9 .

The recovery tube 61 includes a first recovery tube 611 and a second recovery tube 612 . The upstream end of the first collection tube 611 is connected to the superior hepatic inferior vena cava (SH-IVC) or the inferior hepatic inferior vena cava (IH-IVC). A downstream end of the first recovery pipe 611 is connected to the recovery tank 62 . The recovery tank 62 is arranged at a position lower than the organ container 20 . That is, the organ 9 accommodated in the organ container 20 is arranged at a position higher than the recovery tank 62 . Due to the difference in water head between the upstream end and the downstream end of the first recovery pipe 611 caused by this, the water is discharged from the superior hepatic inferior vena cava (SH-IVC) or the inferior hepatic inferior vena cava (IH-IVC). The perfusate thus obtained flows into the recovery tank 62 .

The upstream end of the second recovery pipe 612 is arranged below the recovery tank 62 . A downstream end of the second recovery pipe 612 is connected to the liquid reservoir 30 . The recovery pump 63 is inserted in the second recovery pipe 612 . The recovery pump 63 causes a flow from the upstream side to the downstream side inside the second recovery pipe 612 . As a result, the perfusate temporarily stored in the recovery tank 62 is directed to the liquid storage section 30 via the second recovery pipe 612 .

The gas exchange section 70 performs gas exchange on the liquid flowing through the second recovery pipe 612 . As shown in FIG. 1 , the gas exchange section 70 has a gas exchange module 71 , a gas supply section 72 and a gas discharge section 73 .

FIG. 2 is a diagram schematically showing the internal structure of the gas exchange module 71. As shown in FIG. The gas exchange module 71 is inserted in the second recovery pipe 612 . As shown in FIG. 2, the gas exchange module 71 has a housing 711 and a plurality of hollow fiber membranes 712 arranged inside the housing 711 . Although the number of hollow fiber membranes 712 in FIG. 2 is several, the actual number of hollow fiber membranes 712 is several tens to several hundred. Inside the housing 711 , the space outside the hollow fiber membranes 712 constitutes a liquid phase 701 through which the perfusate in the second collection tube 612 passes. In addition, inside the housing 711, the space inside the hollow fiber membrane 712 constitutes a gas phase 702 through which the gas passes. Each of the hollow fiber membranes 712 is a gas exchange membrane that performs gas exchange between the liquid phase 701 and the gas phase 702 . The hollow fiber membrane 712 is a tubular gas exchange membrane.

Housing 711 has liquid inlet 713 and liquid outlet 714 communicating with liquid phase 701 , and gas inlet 715 and gas outlet 716 communicating with gas phase 702 . The liquid supply port 713 is connected to the upstream side of the second recovery pipe 612 . The liquid outlet 714 is connected to the downstream side of the second recovery pipe 612 . As a result, the liquid supplied from the liquid storage section 30 flows from the liquid supply port 713 , passes through the liquid phase 701 , and is discharged to the liquid discharge port 714 .

The gas supply port 715 is connected to a later-described air supply pipe 721 of the gas supply section 72 . The gas discharge port 716 is connected to an exhaust pipe 731 of the gas discharge portion 73, which will be described later. As a result, the gas supplied from a gas supply source 722 (described later) of the gas supply unit 72 flows in from the gas supply port 715 , passes through the gas phase 702 , and is discharged to the gas discharge port 716 .

With such a configuration, the gas component dissolved in the liquid flowing through the liquid phase 701 and the gas component flowing through the gas phase 702 are exchanged inside the gas exchange module 71 . For example, when the gas supplied to the gas phase 702 is pure oxygen gas, oxygen is supplied to the liquid flowing through the liquid phase 701, and gas components other than oxygen such as carbon dioxide contained in the liquid are added to the gas phase. 702.

The gas supply section 72 has an air supply pipe 721 , a gas supply source 722 , a first valve 723 and a mass flow controller 724 .

The air supply pipe 721 is a pipe for supplying gas to the gas phase 702 of the gas exchange module 71 . An air supply line 721 connects the gas supply source 722 and the gas phase 702 . The upstream end of the air supply pipe 721 is connected to a gas supply source 722 . A downstream end of the air supply pipe 721 is connected to the gas supply port 715 . Thereby, the air supply pipe 721 supplies the gas supplied from the gas supply source 722 to the gas phase 702 of the gas exchange module 71 .

Gas supply source 722 supplies a gas containing at least oxygen. The gas supplied by the gas supply source 722 is, for example, oxygen gas, dry clean air, or the like. The first valve 723 is provided in the air supply pipe 721 and switches the communication state of the air supply pipe 721 between an open state and a closed state. In this embodiment, the first valve 723 is an on-off valve that switches between an open state and a closed state, but a flow control valve that controls the flow rate may be used as the first valve 723 . The mass flow controller 724 controls the flow rate of the gas flowing through the air supply pipe 721 and adjusts it to the set flow rate.

The gas exhaust part 73 has an exhaust pipe 731 and a second valve 732 . The exhaust pipe 731 is a pipe for discharging gas from the gas phase 702 of the gas exchange module 71 . The upstream end of the exhaust pipe 731 is connected to the gas outlet 716 of the gas exchange module 71 . The second valve 732 is provided in the middle of the exhaust pipe 731 or at the downstream end of the exhaust pipe 731 . The second valve 732 switches the communication state of the exhaust pipe 731 between an open state and a closed state. When the second valve 732 is opened, gas is discharged from the gas phase 702 of the gas exchange module 71 to the outside. In the liquid of this embodiment, the second valve 732 is an on-off valve that switches between an open state and a closed state.

The pH measuring section 80 is inserted in the second recovery pipe 612 on the downstream side of the gas exchange module 71 . Thereby, the pH measurement unit 80 measures the pH of the perfusate flowing through the collection tube 61 on the downstream side of the gas exchange module 71 .

The control section 10 controls each section of the organ preservation apparatus 1 . Specifically, the control unit 10 is electrically connected to the first pump 42, the second pump 52, the recovery pump 63, the first valve 723, the mass flow controller 724, the second valve 732, and the pH measuring unit 80. . The first pump 42, the second pump 52, the recovery pump 63, the first valve 723, and the mass flow controller 724 are not electrically connected to the controller 10, and may be manually operated.

The control unit 10 is configured by, for example, an electronic circuit board or a computer including a processor such as a CPU and a memory such as a RAM. The control unit 10 controls the first valve 723 and the second valve 732 based on the measured value of the pH measurement unit 80.

<1-2. pH adjustment of perfusate in perfusion treatment>
Next, a method for adjusting the pH of the perfusate in the perfusion treatment using the organ preservation apparatus 1 will be described with reference to FIG. FIG. 3 is a flow chart showing the flow of perfusion treatment including pH adjustment treatment.

As shown in FIG. 3, first, perfusion treatment is started (step S1). Before the perfusion treatment in step S1, as preparation, the organ 9 is connected to the first liquid supply pipe 41, the second liquid supply pipe 51, and the recovery pipe 61, and the organ 9 is placed in the organ container 20. be done. Then, in step S1, after preparation for the perfusion treatment is completed, the first pump 42, the second pump 52 and the recovery pump 63 are driven, and the supply of the perfusate to the organ 9 is started. At this time, driving of the mass flow controller 724 is started at the same time. The opening degrees of the first valve 723 and the second valve 732 at the start of the perfusion process are set to predetermined opening degrees.

After the perfusion process is started, the pH adjustment process of steps S2 to S4 is repeated. This pH adjustment process utilizes the fact that the carbon dioxide partial pressure in the perfusate changes in the gas exchange unit 70 according to the opening degrees of the first valve 723 and the second valve 732 . The pH adjustment process (steps S2 to S4) is performed, for example, once every second.

Specifically, in the perfusion process, the organ 9 breathes, consumes oxygen, and generates carbon dioxide. Therefore, if gas exchange is not performed by the gas exchange unit 70, the partial pressure of carbon dioxide in the perfusate increases and the perfusate becomes more acidic, resulting in a lower pH. Therefore, for example, if both or one of the first valve 723 and the second valve 732 in the gas exchange section 70 is closed, the pH of the perfusate becomes low. On the other hand, when both the first valve 723 and the second valve 732 are opened, the carbon dioxide in the perfusate in the liquid phase 701 shifts to the gas phase 702 in the gas exchange section 70, and the gas in the gas phase 702 of oxygen migrates to the perfusate in the liquid phase 701 . As a result, the partial pressure of carbon dioxide in the perfusate decreases and the perfusate tends to become alkaline, resulting in an increase in pH. Using this principle, pH adjustment processing (steps S2 to S4) is performed.

In the pH adjustment process (steps S2 to S4), the control unit 10 first measures the pH of the perfusate in the collection tube 61 by the pH measurement unit 80 (step S2).

Subsequently, the control unit 10 determines the opening degrees of the first valve 723 and the second valve 732 based on the measured value of the pH measuring unit 80 in step S2 (step S3).

Here, a method for determining the opening degrees of the first valve 723 and the second valve 732 in step S3 will be described with reference to FIG. FIG. 4 is a flow chart showing the flow of the opening degree determination step in the pH adjustment process. In this embodiment, in the pH adjustment process, the opening of one of the first valve 723 and the second valve 732 is kept fixed, and the opening of the other is adjusted. A case will be described below in which the degree of opening of the first valve 723 is changed while the degree of opening of the second valve 732 remains 100% open.

In the opening degree determination step (step S3), the control unit 10 first determines whether or not the value measured by the pH measurement unit 80 is equal to or less than the first threshold (step S31). The first threshold is, for example, pH 7.36, which is the lower limit of the appropriate pH range. In step S31, if the measured pH value is equal to or less than the first threshold value (step S31: Yes), it is determined to increase the opening of the first valve 723 (step S32), and step S3 ends. This promotes the discharge of carbon dioxide in the perfusate in the gas exchange section 70 .

On the other hand, in step S31, when the measured pH value is greater than the first threshold (step S31: No), the control unit 10 determines whether the value measured by the pH measurement unit 80 is equal to or greater than the second threshold. (step S33). The second threshold is, for example, 7.42, which is the upper limit of the proper pH range. In step S33, when the measured pH value is equal to or greater than the second threshold (step S33: Yes), it is determined to lower the opening of the first valve 723 (step S34), and step S3 is terminated. This suppresses the discharge of carbon dioxide in the perfusate in the gas exchange unit 70 . In step S33, if the measured pH value is smaller than the second threshold (step S33: No), the controller 10 does not change the opening of the first valve 723, and ends step S3.

Then, the control section 10 changes the opening degree of the first valve 723 of the gas exchange section 70 based on the opening degree determined in step S3 (step S4). Thus, the control unit 10 controls the first valve 723 based on the measured value of the pH measurement unit 80.

In this way, the control unit 10 opens the second valve 732 100%, and increases the degree of opening of the first valve 723 when the pH value measured by the pH measuring unit 80 decreases. As a result, a gas containing oxygen gas is supplied to the gas phase 702 of the gas exchange module 71, oxygen is supplied to the perfusate in the liquid phase 701, and carbon dioxide is discharged. As a result, the carbon dioxide partial pressure of the perfusate flowing through the organ preservation apparatus 1 decreases, and the pH of the perfusate increases.

On the other hand, the control unit 10 opens the second valve 732 100%, and decreases the degree of opening of the first valve 723 when the pH value measured by the pH measuring unit 80 increases. As a result, gas containing oxygen gas is no longer supplied to the gas phase 702 of the gas exchange module 71, and carbon dioxide in the liquid phase 701 is no longer discharged. As a result, carbon dioxide discharged from the organ 9 is gradually accumulated in the perfusate, the carbon dioxide partial pressure of the perfusate flowing through the organ preservation apparatus 1 increases, and the pH of the perfusate decreases.

In the perfusion process of the organ 9, by adjusting the opening degree of the first valve 723 based on the measured value of the pH measurement unit 80, the carbon dioxide partial pressure of the perfusate can be adjusted without using a complicated control mechanism. and pH can be adjusted appropriately.

In the above description, the degree of opening of the second valve 732 is fixed and the degree of opening of the first valve 723 is changed, but the present invention is not limited to this. The opening degree of the first valve 723 may be fixed and the opening degree of the second valve 732 may be changed. In that case, in step S<b>32 , the control unit 10 decides to increase the opening of the second valve 732 instead of increasing the opening of the first valve 723 . Further, in step S<b>34 , instead of deciding to lower the opening of the first valve 723 , the control unit 10 decides to lower the opening of the second valve 732 .

Specifically, the control unit 10 opens the first valve 723 100%, and increases the degree of opening of the second valve 732 when the pH value measured by the pH measuring unit 80 decreases. As a result, gas is discharged from the gas phase 702 of the gas exchange module 71, thereby promoting the supply of gas containing oxygen gas, supplying oxygen to the perfusate in the liquid phase 701, and discharging carbon dioxide. be done. As a result, the carbon dioxide partial pressure of the perfusate flowing through the organ preservation apparatus 1 decreases, and the pH of the perfusate increases.

On the other hand, the control unit 10 opens the first valve 723 100%, and decreases the degree of opening of the second valve 732 when the pH value measured by the pH measuring unit 80 increases. As a result, the discharge of the gas from the gas phase 702 of the gas exchange module 71 is stopped, so that the supply of the gas containing the oxygen gas is delayed and the carbon dioxide in the liquid phase 701 is hardly discharged. As a result, carbon dioxide discharged from the organ 9 is gradually accumulated in the perfusate, the carbon dioxide partial pressure of the perfusate flowing through the organ preservation apparatus 1 increases, and the pH of the perfusate decreases.

Next, “increasing the degree of opening” and “decreasing the degree of opening” of the first valve 723 or the second valve 732 will be described. The first valve 723 and the second valve 732 of this embodiment are opening/closing valves for opening/closing the air supply pipe 721 and the exhaust pipe 731, respectively.

As in this embodiment, when the first valve 723 and the second valve 732 are open/close valves, the degree of opening may be set in two stages, "open state" and "closed state." In this case, "increase opening" opens the valve if it is closed, or keeps the valve open if it is already open. "Decrease degree of opening" closes the valve if it is open, and maintains the closed state of the valve if it is already closed.

Further, when the first valve 723 and the second valve 732 are open/close valves as in the present embodiment, the opening and closing of the valves 723 and 732 may be repeated periodically, and the ratio of the open time may be used as the degree of opening. Specifically, for example, when one cycle is 100 msec, the valve is continuously closed at an opening of 0%, and repeatedly opens for 30 msec and closes for 70 msec at an opening of 30%. At 50% opening, 50 msec opening and 50 msec closing are repeated. At the opening degree of 100%, the open state is maintained continuously. In this way, even when the first valve 723 and the second valve 732 are open/close valves, it is possible to set a plurality of stages of opening.

Note that the first valve 723 and the second valve 732 may be flow control valves instead of opening/closing valves. In that case, the opening can be adjusted by changing the flow rate. Further, only one of the first valve 723 and the second valve 732 that changes the degree of opening in the pH adjustment process may be a flow control valve.

<2. Second Embodiment>
FIG. 5 is a diagram showing the configuration of an organ preservation apparatus 1A according to the second embodiment. In the organ preservation apparatus 1 according to the first embodiment, the perfusate is supplied from the liquid reservoir 30 to the organ 9 by a pump. The supply of perfusate to organ 9A is performed by a hydraulic head difference. In the following, in the second embodiment, components different from those in the first embodiment will be described, and descriptions of the same components will be omitted.

As shown in FIG. 5, the organ preservation apparatus 1A of this embodiment includes an organ container 20A, a liquid storage section 30A, a first liquid supply section 40A, a second liquid supply section 50A, a liquid recovery section 60A, and a gas exchange section 70A. , a pH measurement unit 80A, and a control unit 10A.

The organ container 20A accommodates the excised organ 9 . Perfusate is stored in the liquid storage part 30A. The first liquid supply section 40A has a first liquid supply pipe 41A and a first air trap 43A. The second liquid supply section 50A has a second liquid supply pipe 51A and a second air trap 53A.

The liquid recovery section 60A has a recovery pipe 61A and a recovery pump 62A. The gas exchange module 71A of the gas exchange section 70A and the pH measurement section 80A are inserted into the recovery pipe 61A, as in the first embodiment. The gas exchange section 70A and the pH measurement section 80A are the same as the gas exchange section 70 and the pH measurement section 80 of the first embodiment. The control unit 10A controls the first valve 723A and the second valve 732A based on the measured value of the pH measurement unit 80A.

The downstream end of the first liquid supply pipe 41A and the downstream end of the second liquid supply pipe 51A are connected to the portal vein and hepatic artery of the liver, which is the organ 9, as in the first embodiment. Connected. On the other hand, in the present embodiment, both the superior hepatic inferior vena cava (SH-IVC) and the inferior hepatic inferior vena cava (IH-IVC) are open without being connected to the duct. Therefore, the perfusate supplied from the liquid reservoir 30A flows through the organ 9, and then is discharged from the superior hepatic inferior vena cava (SH-IVC) and the inferior hepatic inferior vena cava (IH-IVC). It accumulates in the lower part of container 20A. The upstream end of the collection tube 61A is arranged below the organ container 20A. As a result, the perfusate accumulated in the organ container 20A is sucked by the recovery pump 62A and returned to the liquid reservoir 30A.

As in the second embodiment, the liquid supply units 40A and 50A may not have pumps, and the irrigation liquid may be supplied by the difference in hydraulic head. In this way, pressure is applied to the blood vessels in the organ 9 and the burden on the organ 9 is suppressed. Furthermore, in recovering the perfusate, the perfusate is discharged naturally from the organ 9 without being sucked by a pump. As a result, the blood vessels of the organ 9 are prevented from being burdened by the suction.

<3. Experiment results>
Next, results of experiments using the organ preservation apparatus 1 of the first embodiment will be described. In Experiments 1 and 2 below, changes in the pH of the perfusate due to closing and opening of the first valve 723 and the second valve 732 were investigated.

<3-1. Experiment 1>
In the organ preservation apparatus 1 of the first embodiment, porcine liver was perfused using an ETK solution as the perfusate. FIG. 6 is a diagram showing the results of Experiment 1. FIG. The upper part of FIG. 6 shows the results of Experiment 1-1. The lower part of FIG. 6 shows the results of Experiment 1-2.

(Experiment 1-1)
In the perfusion treatment, the perfusion treatment was performed with the first valve 723 opened and the second valve 732 closed. Then, after the measured value of pH falls below the lower limit pH 7.36 of the appropriate range, the second valve 732 is opened, and immediately after the opening (elapsed time 0 min) and after 5 minutes (elapsed time 5 min), the gas The pH and carbon dioxide partial pressure (pCO ₂ ) of the perfusate downstream of the exchange section 70 were measured.

As shown in the upper part of FIG. 6, the pH value increases and the carbon dioxide partial pressure value decreases during the elapsed time from 0 min to 5 min. From this, it can be seen that when both the first valve 723 and the second valve 732 are open, the pH value increases due to the decrease in the partial pressure of carbon dioxide in the perfusate.

(Experiment 1-2)
In the perfusion treatment, the perfusion treatment was performed with the first valve 723 and the second valve 732 opened. Then, after the measured value of pH exceeds the upper limit pH 7.42 of the appropriate range, the second valve 732 is closed, and immediately after closing (elapsed time 0 min), after 30 minutes (elapsed time 30 min), and 60 minutes After the passage of time (60 minutes elapsed time), the pH and carbon dioxide partial pressure (pCO ₂ ) of the perfusate on the downstream side of the gas exchange section 70 were measured.

As shown in the lower part of FIG. 6, the pH value gradually decreases and the carbon dioxide partial pressure value gradually increases from the elapsed time of 0 min to 30 min and 60 min. From this, it can be seen that when the first valve 723 is in the open state and the second valve 732 is in the closed state, the carbon dioxide partial pressure in the perfusate increases, thereby decreasing the pH value.

<3-2. Experiment 2>
In the organ preservation apparatus 1 of the first embodiment, porcine liver was perfused using an ETK solution as the perfusate. During perfusion, the second valve 732 was always open, and the first valve 723 was switched between open and closed states. Further, the pH and bicarbonate ion (HCO ₃ ⁻ ) concentration of the perfusate on the downstream side of the gas exchange unit 70 were measured eight times during the perfusion treatment.

FIG. 7 is a diagram showing the results of Experiment 2. FIG. The upper part of FIG. 7 shows the opening/closing state of the first valve 723 on the horizontal axis (time) common to the lower part. In the lower part of FIG. 7, the measured pH value of the perfusate is indicated by a black polygonal line, and the bicarbonate ion (HCO ₃ ⁻ ) concentration is indicated by a gray polygonal line.

As shown in FIG. 7, the pH value increases and the bicarbonate ion concentration decreases during the open period of the first valve 723, and the pH value decreases and the bicarbonate ion concentration decreases during the closed period of the first valve 723. An increase in concentration was observed.

In the perfusion treatment, the respiration of the organ 9 increases the carbon dioxide partial pressure and the bicarbonate ion concentration in the perfusate. descend. From Experiment 1 and Experiment 2 above, when either one of the first valve 723 and the second valve 732 is closed, even if the other is open, the partial pressure of carbon dioxide in the perfusate and the It was found that the pH value decreased due to the increased bicarbonate ion concentration. On the other hand, it was found that when both the first valve 723 and the second valve 732 were opened, the carbon dioxide and bicarbonate ions in the perfusate were discharged and the pH increased.

<4. Variation>
Although one embodiment of the present invention has been described above, the present invention is not limited to the above embodiment.

Although the organ preservation apparatus 1 of the above embodiment has two liquid supply units 40, 50 and two liquid supply tubes 41, 51, the present invention is not limited to this. There may be one liquid supply section and one liquid supply tube.

Further, in the above embodiment, the gas exchange section 70 and the pH measurement section 80 are provided in the recovery pipe 61 of the liquid recovery section 60, but the present invention is not limited to this. The gas exchange section and the pH measurement section may be provided in the liquid supply pipe of the liquid supply section. In the above embodiment, the two liquid supply units 40 and 50 and the two liquid supply pipes 41 and 51 are provided. set is required. However, when there is one liquid supply section and one liquid supply pipe, one set of gas exchange section and pH measurement section may be provided in the liquid supply pipe.

Also, the detailed structure of the organ preservation device does not have to completely match the structure shown in each figure of the present application. Also, the elements appearing in the above embodiments and modified examples may be appropriately combined within a range that does not cause contradiction.

Reference Signs List 1, 1A organ preservation device 9, 9A organ 10, 10A control unit 30, 30A liquid storage unit 41, 41A first liquid supply pipe 51, 51A second liquid supply pipe 61, 61A recovery pipe 70, 70A gas exchange unit 71, 71A gas exchange module 80, 80A pH measurement unit 701 liquid phase 702 gas phase 712 hollow fiber membrane 721 air supply pipe 723, 723A first valve 731 exhaust pipe 732, 732A second valve

Claims (6)

An organ preservation device for preserving an organ while perfusing the organ with a liquid outside the body,
a liquid storage part in which the liquid is stored;
a pipe for circulating the liquid between the liquid reservoir and the organ;
a pH measuring unit inserted into the pipe;
a gas exchange unit that performs gas exchange with respect to the liquid flowing through the pipe;
a control unit;
has
The gas exchange part is
a liquid phase through which the liquid in the pipe passes;
a gas phase through which the gas passes;
a gas exchange membrane for gas exchange between the liquid phase and the gas phase;
a gas supply source that supplies a gas containing oxygen to the gas phase;
a first valve provided in an air supply pipe that connects the gas supply source and the gas phase;
a second valve provided in an exhaust pipe for discharging gas from the gas phase;
including
The organ preservation apparatus, wherein the control unit controls the first valve and the second valve based on the measured value of the pH measurement unit. The organ preservation device according to claim 1,
The control unit
While opening the second valve,
When the pH value measured by the pH measuring unit decreases, the degree of opening of the first valve is increased,
The organ preservation apparatus, wherein the degree of opening of the first valve is reduced when the pH value measured by the pH measurement unit increases. The organ preservation device according to claim 1,
The control unit
While opening the first valve,
When the pH value measured by the pH measuring unit decreases, the degree of opening of the second valve is increased,
The organ preservation apparatus, wherein the degree of opening of the second valve is decreased when the pH value measured by the pH measuring unit increases. An organ preservation method for preserving an organ while perfusing the organ with a liquid outside the body,
A perfusion step of circulating the liquid through a pipe between a liquid reservoir in which the liquid is reserved and the organ,
A gas exchange unit is inserted in the pipe,
The gas exchange part is
a liquid phase through which the liquid in the pipe passes;
a gas phase through which the gas passes;
a gas exchange membrane for gas exchange between the liquid phase and the gas phase;
a gas supply source that supplies a gas containing oxygen to the gas phase;
a first valve provided in an intake pipe that connects the gas supply source and the gas phase;
a second valve provided in an exhaust pipe for discharging gas from the gas phase;
has
During the perfusion step,
a) measuring the pH of the liquid in the pipe;
b) controlling the first valve and the second valve based on the measurements in step a);
A method of organ preservation in which is performed. The organ preservation method according to claim 4,
In the perfusion step, while opening the second valve,
In step b),
When the pH value measured in step a) decreases, the degree of opening of the first valve is increased,
A method for preserving organs, wherein the degree of opening of the first valve is reduced when the pH value measured in step a) increases. The organ preservation method according to claim 4,
In the perfusion step, while opening the first valve,
In step b),
When the pH value measured in step a) decreases, the degree of opening of the second valve is increased,
A method for preserving organs, wherein the degree of opening of the second valve is decreased when the pH value measured in step a) increases.

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