A recirculating perfusion system for multi-organ life support

Abstract

The application discloses a circulating perfusion system for multi-organ life support, wherein a power unit is used for driving circulating flow of perfusion liquid; an oxygenation unit comprises an oxygenator and a heat exchanger; a blood storage unit is used for providing capacity buffer and collecting backflow perfusion liquid; a multi-organ access assembly makes a multi-organ whole body access a main circulating loop composed of the power unit, the oxygenation unit and the blood storage unit; the multi-organ whole body comprises multiple organs and retains original vascular connection structure among the organs; a global monitoring unit is used for monitoring whole body operation parameters in the main circulating loop; and a control unit is used for overall regulation and control of the main circulating loop based on the whole body operation parameters. The application constructs a unified circulating perfusion system for multi-organ life support scene, carries out integrated perfusion and whole body state monitoring on multiple organs as an indivisible whole, avoids independent flow / pressure regulation on each organ, and thus realizes cooperative support close to a physiological state.

Description

Technical Field

[0001] This invention relates to the field of medical devices and life support technology, specifically to a circulatory perfusion system for multi-organ life support. Background Technology

[0002] With advancements in organ transplantation, critical care medicine, and new drug development, the demand for extracorporeal life support for ex vivo or failing organs is increasing. Traditional extracorporeal life support technologies, such as extracorporeal membrane oxygenation (ECMO) or single-organ perfusion systems (such as ex vivo liver perfusion machines), are primarily designed for single-organ or systemic circulatory support. However, when faced with complex research scenarios involving multi-organ transplantation, treatment of multiple organ failure, or the need to study inter-organ interactions, existing technologies reveal fundamental limitations.

[0003] Current approaches attempt to simply connect multiple single-organ perfusion devices in parallel to form a "piecemeal" multi-organ perfusion system. The core idea of ​​this approach is to equip each organ with an independent pump, oxygenator, sensor array, and controller, attempting to independently and precisely control the perfusion flow and pressure for each organ. However, this approach suffers from the following fundamental flaws:

[0004] First, the system is complex and prone to instability; any local adjustment can trigger coupled oscillations through the shared loop. Each additional organ requires a complete perfusion unit, resulting in bulky equipment, complex tubing, complicated operation, and numerous potential points of failure. At the same time, multiple independent closed loops coupled through a shared blood reservoir and tubing are prone to mutual interference and oscillations, leading to poor system robustness.

[0005] Second, it artificially severs the physiological connections between organs. In the body, all organs share the same circulatory environment. The liver's metabolic products affect the kidneys, and the heart's pumping action simultaneously affects all organs, including the liver, kidneys, and intestines. However, the independent perfusion protocol isolates each organ in its own independent circuit, disrupting this natural multi-organ interaction and feedback relationship, resulting in a significant deviation between perfusion results and physiological state.

[0006] Therefore, existing technologies in the field of multi-organ support suffer from bottlenecks such as "system fragmentation, non-physiological perfusion, and complex control," and there is an urgent need for a circulatory perfusion system that can integrate multiple organs as a whole for perfusion and overall status monitoring. Summary of the Invention

[0007] To address the aforementioned problems, the purpose of this invention is to propose a circulatory perfusion system for multi-organ life support. This system constructs a unified circulatory perfusion system for multi-organ life support scenarios, treating multiple organs as an inseparable whole for integrated perfusion and overall status monitoring. This avoids independent flow / pressure regulation of each organ, thereby achieving synergistic support close to physiological conditions.

[0008] This was achieved through the following technical solutions:

[0009] A circulatory perfusion system for multi-organ life support, used for integrated circulatory perfusion of isolated multi-organ systems, characterized in that the system includes a power unit, an oxygenation unit, a blood storage unit, a multi-organ access component, a global monitoring unit, and a control unit;

[0010] The power unit consists of a single central pump, which drives the injection fluid to circulate in the system;

[0011] The oxygenation unit includes an oxygenator and a heat exchanger. The oxygenator is used to exchange gases in the infusion fluid, and the heat exchanger is used to regulate the temperature of the infusion fluid.

[0012] The blood storage unit is used to provide a volume buffer and collect the returned perfusion fluid;

[0013] The multi-organ access component includes a total input arterial line and a total output venous line, which are used to connect to the arterial inlet and venous outlet of the multi-organ system, respectively, so that the multi-organ system can be connected to the main circulation loop composed of a power unit, an oxygenation unit, and a blood storage unit.

[0014] A multi-organ system includes multiple organs and retains the original vascular connections between the organs;

[0015] The global monitoring unit is used to monitor the overall operating parameters in the main loop.

[0016] The control unit is electrically connected to the power unit and the oxygenation unit, and is used to perform overall regulation of the main circulation loop based on the overall operating parameters.

[0017] Optionally, the overall operating parameters include at least one of the following: circulating flow rate, arterial pressure, venous pressure, temperature, blood oxygen saturation, pH value, lactate concentration, and electrolyte concentration.

[0018] Optionally, the control unit achieves overall regulation by adjusting at least one of the following parameters: the rotational speed of a single central pump; the gas flow rate or gas ratio of the oxygenator; and the temperature setting of the heat exchanger.

[0019] Optionally, it also includes a pulsation generating device for generating pulsating flow in the main circulation loop.

[0020] Optionally, the pulsation generating device generates pulsation in at least one of the following ways: a variable volume chamber disposed in the outlet of the central pump or in the main circulation loop, and a drive mechanism for driving the periodic change of the variable volume chamber; a control module for periodically modulating the rotational speed of the central pump; and a combination structure of a one-way valve and an elastic energy storage chamber disposed in the main circulation loop.

[0021] Optionally, the pulsation parameters of the pulsation generating device include pulsation waveform and pulsation frequency, both of which are configured to simulate the physiological arterial pulsation characteristics of the target species.

[0022] Alternatively, the single central pump can be a magnetic levitation pump or a centrifugal pump.

[0023] Optionally, the multi-organ whole includes at least one of the following combinations: heart, lung, liver, and kidney; heart, liver, and lung; liver and kidney; and the original vascular connections between the organs are preserved.

[0024] Optionally, an oxygenator is installed on the circulation line between the blood storage unit and the multi-organ system to oxygenate the returned perfusion fluid.

[0025] Optionally, a metabolite detection unit is also provided in the tubing that connects multiple organs to the main circulation loop to detect the overall metabolite concentration.

[0026] The beneficial effects of this invention compared to the prior art are:

[0027] 1) It highly replicates the physiological synergy environment of multiple organs, preserves the original vascular connections between organs, allows all organs to share the same circulatory loop, and enables the transfer of metabolic products across organs, avoiding physiological deviations caused by isolated perfusion. It realistically simulates the interaction and feedback relationship of multiple organs in vivo, and is especially suitable for joint transplantation and organ interaction research.

[0028] 2) The system architecture is relatively simple, and the operation is convenient and reliable. Only a few devices such as a single pump, a single oxygenator, and a single blood collection device are needed to support the overall ex vivo operation of multiple organs. There is no need to configure independent pumps, valves and pipelines for each organ, which greatly reduces the size of the equipment and the number of failure points. Operators also do not need to insert cannulas and adjust parameters for each organ, which significantly reduces the complexity of operation and clinical preparation time.

[0029] 3) The system only needs to maintain stable overall operating parameters. The control algorithm is simple and reliable. It is not limited to organ combinations and can be flexibly connected to different multi-organ systems such as liver-kidney, heart-liver-kidney, etc. It has excellent scalability and is suitable for a variety of medical and scientific research scenarios. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of a circulatory perfusion system for multi-organ life support.

[0031] Figure 2 This is a schematic diagram illustrating three implementation methods of a pulsation generator in a circulatory perfusion system for multi-organ life support.

[0032] Figure 3 This is a flowchart illustrating the implementation method of a circulatory perfusion system for multi-organ life support. Detailed Implementation

[0033] The technical solutions in the embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0034] like Figure 1 The diagram shows a schematic of a circulatory perfusion system for multi-organ life support, which mainly includes a power unit, an oxygenation unit, a blood storage unit, a multi-organ access component, a global monitoring unit, and a control unit. It is used to perform integrated circulatory perfusion on isolated multi-organ systems (this application takes isolated multi-organ systems from pigs as an example) to achieve synergistic support close to physiological conditions.

[0035] In this embodiment, the power unit consists of a single central pump, which can be a magnetic levitation pump. The power unit, controlled by a control unit, drives the perfusion fluid to circulate within the system. A blood storage unit is located between the oxygenation unit and the multi-organ access assembly. It provides a volume buffer and collects the returned perfusion fluid, thereby stabilizing loop pressure fluctuations. The blood storage unit can be a blood tank or a flexible reservoir structure.

[0036] The oxygenation unit is located in the circulation pipeline between the multi-organ system and the blood storage unit, and is used to oxygenate the returned perfusion fluid. The oxygenation unit specifically includes an oxygenator and a heat exchanger. The oxygenator performs gas exchange with the perfusion fluid, and the heat exchanger regulates the temperature of the perfusion fluid. The oxygenator includes interconnected membrane lungs and an air-oxygen mixer. The air-oxygen mixer enables air-oxygen exchange in the blood within the membrane lungs through O2 gas tanks, CO2 gas tanks, and external air tanks, and removes ETCO2 gas. The membrane lungs are connected to both the blood storage unit and the multi-organ system to facilitate gas exchange with the perfusion fluid.

[0037] The multi-organ access component includes a total afferent arterial conduit and a total efferent venous conduit, which are used to connect to the arterial inlet and venous outlet of the multi-organ system, respectively, enabling the multi-organ system to access the main circulatory loop composed of a power unit, an oxygenation unit, and a blood storage unit. Through the above connection method, the multi-organ system is effectively connected to the circulatory loop as a whole.

[0038] In this embodiment, the multi-organ system comprises multiple organs while preserving the original vascular connections between them. The multi-organ system can have multiple combinations, such as: heart, lungs, liver, and kidneys; heart, liver, and lungs; liver and kidneys; and each organ retains its original vascular connections. Within the multi-organ system, arterial blood distribution is naturally determined by the preserved original vascular network between each organ and its own vascular resistance, thus preserving as much of the original physiological function of the multi-organ system as possible. During the operation of the circulatory perfusion system, venous blood is first pumped into the lungs via the right heart within the multi-organ system for gas exchange, then oxygenated and returned to the left heart before returning to the main circulatory loop.

[0039] During perfusion, the perfusion fluid enters the multi-organ system through the main infusion artery and is naturally distributed among the organs through the native vascular network. The distribution ratio is automatically regulated by the vascular resistance of each organ. Then, it is collected through the main outflow vein and finally returned to the blood storage unit. This process does not rely on independent flow or pressure control of individual organs.

[0040] The global monitoring unit includes multiple sensors for monitoring overall operating parameters in the main circulation loop. These overall operating parameters include at least one of the following: circulation flow rate, arterial pressure, venous pressure, temperature, blood oxygen saturation (SpO2), pH value, lactate concentration, and electrolyte concentration (such as Na⁺, K⁺, Ca²⁺, etc.). The sensors can be located in the main input artery line, the main output venous line, and the blood storage unit.

[0041] The control unit is electrically connected to the power unit and the oxygenation unit. It is used to regulate the main circulation loop according to the overall operating parameters, keeping the overall operating parameters within a preset physiological range. The control unit can regulate the operation by adjusting the speed of the central pump, the gas flow rate and ratio of the oxygenator, and the temperature setting of the heat exchanger. The control unit provides overall control of the main circulation loop and comprehensive control of multiple organs as a whole, eliminating the need for cumbersome and complex individual adjustments for each organ.

[0042] In this embodiment, the circulating perfusion system also includes a pulsation generator for generating pulsating flow in the main circulation loop. For example... Figure 2 The diagram shown illustrates the principles of three implementation methods for a pulsation generator in a circulatory perfusion system used for multi-organ life support. Figure 2 As shown, the pulsation generating device generates pulsations in at least one of the following ways:

[0043] 1) Method 1: A variable volume chamber is set in the outlet of the central pump or in the main circulation loop, and a drive mechanism is used to drive the periodic change of the variable volume chamber.

[0044] 2) A control module for periodically modulating the speed of the center pump, which generates pulsation by controlling the speed of the center pump;

[0045] 3) A combination structure of a one-way valve and an elastic energy storage chamber is set in the main circulation loop. The one-way valve is connected to the central pump, and the elastic energy storage chamber is connected to the oxygenation unit. The pulsation is triggered by the fluid pressure of the injection fluid and the restoring force of the elastic material itself.

[0046] The pulsation parameters of the pulsation generator include pulsation waveform and pulsation frequency, both of which are configured to simulate the physiological arterial pulsation characteristics of the target species.

[0047] In addition, a metabolite detection unit can be installed in the tubing that connects multiple organs to the main circulation loop (especially at the main artery inlet tubing) to detect the overall concentration of metabolites, such as creatinine, transaminase, and bilirubin, so as to reflect the overall metabolic load and clearance capacity of multiple organs without the need for individual monitoring of each specific organ.

[0048] In this embodiment, based on the aforementioned circulating perfusion system and Figure 3 The flowchart shown is a method for implementing a circulatory perfusion system for multi-organ life support. It uses four organs—exposed pig heart, liver, lung, and kidney—as a whole for case verification. It mainly includes five parts: acquisition and preparation of the whole multi-organ system, connection to the circulatory perfusion system, setting of global monitoring parameters, execution of control strategies, and feedback of perfusion results.

[0049] In the acquisition and preparation of multiple organs as a whole, the first step is to obtain the isolated pig's heart-liver-lung-kidney as a whole. During surgical removal, the anatomical structures of the heart, lungs, liver, kidneys, common blood supply arteries, and common venous return are preserved, and then rinsed and preserved.

[0050] Then, the system is connected, integrating the aforementioned heart-liver-lung-kidney multi-organ system into this circulatory perfusion system, forming a total input arterial line: connected to the thoracic aorta (distal to the ascending aorta). Perfusion fluid enters the coronary arteries (heart) via the aortic root, descends through the celiac trunk to the liver (liver), and enters the kidneys via the renal arteries (kidney). Simultaneously, the pulsating perfusion of the aorta directly acts on the heart, maintaining its natural heartbeat. The total output venous line: connected to the confluence of the superior and inferior vena cava (right atrial inlet). Venous return occurs via the right atrium → right ventricle → pulmonary artery → pulmonary capillaries → pulmonary veins → left atrium. At the left atrial level, blood can naturally overflow through the left atrial appendage or left atrial incision, or return to the blood reservoir through a left atrial drainage tube. (It should be noted that the multi-organ connection here is only for integrating the multi-organ system into the circulatory perfusion system; it only involves the connection method and does not involve surgical treatment of the multi-organ system.)

[0051] Of particular note is that pulmonary circulation is fully preserved in this embodiment. Venous blood is first pumped into the lungs via the right heart for gas exchange. After oxygenated blood returns to the left atrium, it is drained back into the system's blood reservoir via left atrial drainage or natural overflow, completing the circulation. This design realistically simulates the physiological process of systemic-pulmonary circulation in series.

[0052] Continue with system startup and pre-charge. Start the central pump to pre-charge the pipeline to purge gas and establish initial circulation.

[0053] The global monitoring parameters for the main loop are set as shown in Table 1 below:

[0054] Table 1:

[0055] Total circulation flow 3.0–3.5 L / min Total input arterial mean pressure 80–90 mmHg Total venous output pressure (right atrial pressure) 5–10 mmHg Pulse frequency 75 beats / min (consistent with the normal heart rate of pigs) Pulsation amplitude 30–40 mmHg pulsation waveform Artery-like waveform (rapid rise + slow fall) temperature 37°C Arterial oxygen saturation (at the total input artery) >95% Venous oxygen saturation (at the total outflow vein) 60–75% pH 7.35–7.45 lactic acid <2 mmol / L

[0056] In executing the control strategy, the controller adjusts the centrifugal pump (central pump) speed based on feedback from the total input arterial pressure sensor to maintain the mean pressure at approximately 85 mmHg. The pulse parameters are preset to 75 beats / min and an amplitude of 35 mmHg, and are not adjusted during operation. The oxygenator is set to low-flow assist mode (because the lungs themselves have gas exchange capabilities, the oxygenator serves only as a backup or auxiliary). The temperature is maintained at 37°C through closed-loop control of the heat exchanger.

[0057] In the feedback perfusion results, the perfusion lasted for 6 hours, and the following indicators were monitored and evaluated:

[0058] 1) The heart maintains spontaneous beating, with a stable heart rate of 70–80 beats / min and a regular rhythm. Regular pulsations can be seen at the aortic root. Myocardial enzymes (CK-MB, cTnI) do not show a significant increase during perfusion.

[0059] 2) Lungs: Pulmonary circulation is unobstructed. After venous blood is oxygenated through the lungs, arterial blood oxygen saturation is maintained at >95%. Pulmonary vascular resistance is stable, and there are no signs of pulmonary edema.

[0060] 3) Liver function: Bile secretion is continuous, with approximately 15–20 mL of bile perfusion over 6 hours. Transaminase levels (AST, ALT) are slightly elevated but within acceptable range, indicating good liver function.

[0061] 4) Kidneys: Urine output was stable, averaging 30–50 mL per hour. Creatinine and blood urea nitrogen levels remained stable. 5) Overall metabolism: Lactate was maintained at 1.5–2.0 mmol / L, blood glucose was stable (indicating hepatic gluconeogenesis function), and electrolytes (Na⁺, K⁺, Ca²⁺) were maintained within the normal range. It is evident that the circulatory perfusion system effectively maintained the stable operation of the isolated multi-organ system.

[0062] After monitoring and evaluation, the flow rate of the perfusion fluid was gradually reduced and the operation of the entire system was stopped. Finally, the entire system was flushed and the multiple organs were removed as a whole, cleaned and preserved separately.

[0063] In summary, this invention preserves the original vascular connections between multiple organs and integrates them into a unified single-circulation main loop. During system operation, after the perfusion fluid enters through the main infusion artery, it is naturally distributed entirely by the preserved original vascular networks and their own vascular resistance between the organs. The distribution ratio is automatically adjusted by the vascular resistance of each organ, and metabolic products can be freely transferred across organs. This structure and flow mechanism eliminates the physiological deviations caused by isolated perfusion, thus realistically simulating the synergistic support effect of multi-organ interactions and feedback relationships in vivo, making it particularly suitable for combined transplantation and organ interaction studies.

[0064] The above embodiments are merely illustrative of the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solutions based on the technical concept proposed in this invention shall fall within the scope of protection of this invention.

Claims

1. A circulatory perfusion system for multi-organ life support, used for integrated circulatory perfusion of isolated multi-organ systems, characterized in that, The system includes a power unit, an oxygenation unit, a blood storage unit, a multi-organ access component, a global monitoring unit, and a control unit; The power unit consists of a single central pump used to drive the perfusion fluid to circulate in the system; The oxygenation unit includes an oxygenator and a heat exchanger. The oxygenator is used to exchange gases in the infusion fluid, and the heat exchanger is used to regulate the temperature of the infusion fluid. The blood storage unit is used to provide a volume buffer and collect the returned perfusion fluid; The multi-organ access component includes a total input arterial line and a total output venous line, which are used to connect to the arterial inlet and venous outlet of the multi-organ system, respectively, so that the multi-organ system can be connected to the main circulation loop composed of a power unit, an oxygenation unit, and a blood storage unit. The multi-organ system includes multiple organs and retains the original vascular connection structure between the organs; The global monitoring unit is used to monitor the overall operating parameters in the main loop. The control unit is electrically connected to the power unit and the oxygenation unit, and is used to perform overall regulation of the main circulation loop based on the overall operating parameters.

2. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, The overall operating parameters include at least one of the following: circulating flow rate, arterial pressure, venous pressure, temperature, blood oxygen saturation, pH value, lactate concentration, and electrolyte concentration.

3. A circulatory perfusion system for multi-organ life support according to claim 1 or 2, characterized in that, The control unit achieves overall regulation by adjusting at least one of the following parameters: the rotational speed of a single central pump; the gas flow rate or gas ratio of the oxygenator; and the temperature setting of the heat exchanger.

4. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, It also includes a pulsation generator for producing pulsating flow in the main circulation loop.

5. A circulatory perfusion system for multi-organ life support according to claim 4, characterized in that, The pulsation generating device generates pulsations by at least one of the following methods: a variable volume chamber located at the outlet of the central pump or in the main circulation loop, and a drive mechanism for driving the periodic changes of the variable volume chamber. A control module for periodically modulating the speed of a central pump; A combination structure of a one-way valve and an elastic energy storage chamber is installed in the main circulation loop.

6. A circulatory perfusion system for multi-organ life support according to claim 4 or 5, characterized in that, The pulsation parameters of the pulsation generator include pulsation waveform and pulsation frequency, both of which are configured to simulate the physiological arterial pulsation characteristics of the target species.

7. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, The single central pump is either a magnetic levitation pump or a centrifugal pump.

8. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, The multi-organ whole includes at least one of the following combinations: heart, lung, liver, and kidney; heart, liver, and lung; liver and kidney; and each organ retains its original vascular connection.

9. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, An oxygenator is installed on the circulation pipeline between the blood storage unit and the multi-organ system to oxygenate the returned perfusion fluid.

10. A circulatory perfusion system for multi-organ life support according to claim 1, characterized in that, In the tubing that connects multiple organs to the main circulation loop, a metabolite detection unit is also installed to detect the overall metabolite concentration.

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