In-vitro heart repair system and method

Abstract

The invention discloses an in-vitro heart repair system and method. Relates to the technical field of medical instruments, in particular to an in-vitro heart repair system which comprises a perfusion container used for containing and being connected with a perfused in-vitro heart. The pipeline connecting unit is used for connecting the perfusion container with the common carotid artery and the external jugular vein of a receptor animal to form a complete extracorporeal circulation loop; the circulating power unit is arranged on the pipeline connecting unit and is used for driving blood to circulate between the isolated heart in the perfusion container and the acceptor animal; and the detection unit is used for detecting the isolated heart and determining the state of the isolated heart according to the detection result. The in-vivo physiological internal environment can be replicated, and the myocardial cell repairing efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to an extracorporeal heart repair system and method. BACKGROUND

[0002] As the only radical treatment for end-stage heart failure, the clinical demand for heart transplantation continues to rise worldwide. However, the severe shortage of donor hearts has become a core bottleneck restricting the popularization and development of heart transplantation technology. In order to alleviate the shortage of donor hearts, the medical field has gradually explored ways to expand the source of donors, among which Donation after Circulatory Death (DCD) is one of the key directions. DCD donor hearts refer to hearts obtained after the donor's heart circulation has stopped and clinical death has been confirmed. Compared with traditional Donation after Brain Death (DBD) donor hearts, DCD donor hearts have a wider source, covering donors who have circulatory failure due to severe trauma, cerebrovascular accidents, etc., but have not reached the criteria for brain death.

[0003] However, the clinical application of DCD donor hearts faces a difficult core technical problem that cannot be overcome: after the donor's circulation stops, the heart will experience an unavoidable warm ischemia time (WIT), which is the time interval from the interruption of blood supply to the donor heart to the start of cold perfusion or mechanical perfusion preservation. During this period, the myocardial cells stop aerobic metabolism due to hypoxia, and anaerobic metabolites (such as lactic acid) accumulate, while intracellular calcium overload and oxidative stress are intensified, leading to myocardial cell edema, apoptosis, and microvascular damage.

[0004] To solve the problem of warm ischemic injury of DCD donor hearts, the industry has gradually developed ex vivo heart perfusion technology, aiming to provide oxygen and nutrients for the donor heart through extracorporeal mechanical perfusion to achieve damage repair and viability assessment, among which the most representative is the international mainstream ex vivo heart mechanical perfusion system. As a portable mechanical perfusion platform, the core structure of this system includes a sealed perfusion cabin for accommodating the ex vivo heart, a mechanical pumping module (including a special blood pump and an oxygenator) for delivering oxygenated blood and nutrient solution, and a basic monitoring unit for monitoring perfusion pressure, flow rate, and blood lactic acid concentration. Its working principle is to connect the ex vivo donor heart to the system pipeline, and then use a mechanical pump to deliver artificially configured oxygenated perfusion solution to the aorta of the heart, prompting the heart to restart and maintain a low-load working state, while indirectly assessing the viability of the donor heart through monitoring of blood metabolic indicators (such as lactic acid clearance rate) to screen potential transplantable donor hearts.

[0005] Although the existing mechanical perfusion system prolongs the donor heart preservation time to a certain extent, there are still significant defects in the repair and accurate evaluation of DCD donor heart warm ischemic injury. The existing system relies on mechanical oxygenators (such as hollow fiber membrane oxygenators) and artificial perfusion fluid to simulate the circulating environment, which cannot replicate the physiological internal environment in vivo, resulting in low myocardial cell repair efficiency and difficulty in reversing moderate and above warm ischemic injury.

[0006] In summary, there is an urgent need to design a technical solution that can replicate the physiological internal environment in vivo and improve the efficiency of myocardial cell repair. SUMMARY

[0007] The purpose of the present application is to provide an extracorporeal heart repair system and method to solve the problems of the prior art, which can replicate the physiological internal environment in vivo and improve the efficiency of myocardial cell repair.

[0008] To achieve the above-mentioned purpose, the present application provides the following solutions: The present application provides an extracorporeal heart repair system, comprising: a perfusion container for containing and connecting a perfused isolated heart; a pipeline connection unit for connecting the perfusion container with the common carotid artery and external jugular vein of a recipient animal to form a complete extracorporeal circulation loop; a circulation power unit provided on the pipeline connection unit for driving blood circulation between the isolated heart in the perfusion container and the recipient animal; and a detection unit for detecting the isolated heart and determining the state of the isolated heart accordingly.

[0009] Preferably, the perfusion container comprises a perfusion tank capable of being sealed, which is used to contain the isolated heart; an inlet is formed at the top of the perfusion tank, and an outlet is formed at the bottom, and sealing devices are provided at the inlet and outlet; the common carotid artery of the recipient animal is connected with the aorta of the isolated heart through the pipeline connection unit provided in the inlet; and the external jugular vein of the recipient animal is connected with the outlet.

[0010] Preferably, the pipeline connection unit comprises a first pipeline and a second pipeline; one end of the first pipeline is connected with the common carotid artery of the recipient animal, the other end passes through the inlet and is connected with the aorta of the isolated heart; one end of the second pipeline is connected with the external jugular vein of the recipient animal, and the other end is connected with the outlet.

[0011] Preferably, the circulation power unit comprises a peristaltic pump, and at least two peristaltic pumps are provided on the pipeline connection unit.

[0012] Preferably, the detection unit comprises a biopsy device and an ultrasound device; the perfusion tank is provided with a biopsy opening and an ultrasound detection opening, and each of the biopsy opening and the ultrasound detection opening is provided with a sealing plug, and the sealing plug is provided with an opening through which the biopsy device or the ultrasound device can be inserted to perform biopsy or ultrasound detection on the isolated heart.

[0013] Preferably, the detection unit further comprises a pressure sensor and a blood oxygen monitor located at the inflow end of the aorta of the isolated heart, and a blood detection instrument for collecting and detecting the perfusion blood.

[0014] Preferably, the perfusion tank is provided with a heat preservation layer, and the heat preservation layer is connected with a circulating heating device to maintain the internal temperature of the perfusion tank at a set temperature.

[0015] Preferably, a water bath heating device is further provided, and the pipeline connection unit between the perfusion container and the recipient animal passes through the water bath heating device so that the blood in the pipeline connection unit is heated to a set temperature.

[0016] Preferably, the perfusion tank is provided with a perfusion cover connected to the top of the perfusion tank, and the inlet, the biopsy opening and the ultrasound detection opening are formed in the perfusion cover; and the perfusion tank is made of a medical transparent material.

[0017] The application further provides an isolated heart repair method using the isolated heart repair system, comprising the following steps: Anesthetizing a healthy recipient animal, and performing a surgery to expose and cannulate the common carotid artery and the external jugular vein of the recipient animal; connecting the aortic root of the isolated heart with the pipeline connection unit; Placing the isolated heart into the perfusion container, starting the circulating power unit, and pumping the arterial blood of the recipient animal into the aorta of the isolated heart, and finally dropping from the pulmonary artery or the right atrium to the bottom of the perfusion container; Pumping the blood at the bottom of the perfusion container back to the external jugular vein of the recipient animal through the outlet; During the perfusion process, the detection unit is turned on, the function recovery state of the isolated heart is judged according to the comprehensive evaluation of the detection indexes, and it is determined whether the isolated heart can be used for transplantation.

[0018] The application has the following technical effects compared with the prior art: The present application is an extracorporeal circulation loop formed by connecting a biological metabolism oxygenation support unit with a healthy recipient animal as the core and a heart containing and repairing unit with a perfusion container as the core through a circulating power unit and a pipeline connection unit. Blood is drawn from the common carotid artery of the healthy recipient animal, which is the biological oxygenator and metabolism center of the system, and its function is to provide oxygen and nutrients for circulating blood and metabolize waste. Unlike the use of artificial perfusion fluid, the present application uses recipient animal whole blood for perfusion, which contains various cells, hormones, nutrients and buffer systems, providing a more physiological internal environment that is conducive to more effective repair and recovery of myocardial cells from thermal ischemic injury and improves the quality of ex vivo heart function recovery. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed in the embodiments. Obviously, the drawings described below are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0020] Figure 1 It is a schematic diagram of the extracorporeal heart repair system in one or some embodiments of the present application. Figure 2 It is a schematic diagram of the blood flow process in the extracorporeal heart repair method in one or some embodiments of the present application.

[0021] In the figure: 1-perfusion tank, 101-inlet, 102-outlet, 2-recipient animal, 3-first pipeline, 4-second pipeline, 5-first peristaltic pump, 6-second peristaltic pump, 7-ex vivo heart, 8-biopsy device, 9-ultrasound device, 10-water bath heating device. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0023] The purpose of the present application is to provide an extracorporeal heart repair system and method to solve the problems in the prior art and to reproduce the physiological internal environment in vivo to improve the repair efficiency of myocardial cells.

[0024] In order to make the above-mentioned purposes, features and advantages of the present application more apparent and easy to understand, the present application will be further described in detail below with reference to the drawings and specific embodiments.

[0025] The existing mechanical perfusion system still has significant defects in the repair and accurate evaluation of DCD heart warm ischemia injury. The existing mechanical perfusion system relies on mechanical oxygenators (such as hollow fiber membrane oxygenators) and artificial perfusion fluid to simulate the circulating environment, which cannot replicate the physiological internal environment in vivo, resulting in low myocardial cell repair efficiency and difficulty in reversing moderate and above warm ischemia injury. In order to solve this problem, the present application provides an extracorporeal heart repair system, as shown in Figure 1 and Figure 2 , which comprises a perfusion container, a pipeline connection unit, a circulating power unit and a detection unit. The perfusion container is used to accommodate and connect the perfused isolated heart 7. The pipeline connection unit is used to connect the perfusion container with the common carotid artery and the external jugular vein of the recipient animal 2 respectively, forming a complete extracorporeal circulation loop. The circulating power unit is arranged on the pipeline connection unit and is used to drive the blood circulation between the isolated heart in the perfusion container and the recipient animal 2. The detection unit is used to detect the isolated heart and determine the state of the isolated heart accordingly. The present application takes the healthy recipient animal 2 as the core of the biological metabolic oxygenation support unit and takes the perfusion container as the core of the heart accommodation and repair unit. The two are connected through the circulating power unit and the pipeline connection unit to form a complete closed-loop extracorporeal circulation loop. The blood is drawn from the common carotid artery of the healthy recipient animal 2, which serves as the biological oxygenator and metabolic center of the system. Its function is to provide oxygen and nutrients for circulating blood and metabolize waste. Unlike the use of artificial perfusion fluid, the present application uses whole blood of the recipient animal 2 for perfusion, which contains various cells, hormones, nutrients and buffer systems, providing a more physiological internal environment, which is conducive to the more effective repair and recovery of myocardial cells from warm ischemia injury and improves the quality of functional recovery of the isolated heart 7.

[0026] In an embodiment, the perfusion container comprises a perfusion tank 1 capable of being sealingly arranged, which is used to accommodate the isolated heart 7. An inlet 101 is formed on the top of the perfusion tank 1, and an outlet 102 is formed on the bottom. Sealing devices are arranged at the inlet 101 and the outlet 102, which can be sealing rings or sealing pads, so that the perfusion tank 1 will not leak. The common carotid artery of the recipient animal 2 is connected with the aorta of the isolated heart 7 through the pipeline connection unit arranged at the inlet 101. A perfusion cover is sealingly connected to the top of the perfusion tank 1, and the inlet 101, the biopsy port and the ultrasonic detection port are all formed on the perfusion cover. The perfusion tank 1 is made of medical transparent material, which is convenient for observing the state of the isolated heart 7. The external jugular vein of the recipient animal 2 is connected with the outlet 102. The blood enters the isolated heart 7 along the pipeline connection unit from the common carotid artery of the recipient animal 2, then drops to the bottom of the perfusion tank 1 through the right atrium of the isolated heart 7, and finally flows back to the external jugular vein of the recipient animal 2 through the outlet 102 at the bottom of the perfusion tank 1, realizing the circulation of blood in the extracorporeal circulation loop, and achieving the repair of the isolated heart 7 through this process.

[0027] In order to make the blood circulation process has the required pressure, therefore, in an embodiment, the pipeline connection unit comprises a first pipeline 3 and a second pipeline 4; one end of the first pipeline 3 communicates with the common carotid artery of the recipient animal 2, the other end passes through the inlet 101, and communicates with the aorta of the isolated heart 7, the first pipeline 3 is fixed and sealed between the outer wall provided at the inlet 101 and the inlet 101 by using a sealing ring; one end of the second pipeline 4 communicates with the external jugular vein of the recipient animal 2, and the other end communicates with the outlet 102; the circulation power unit of the embodiment comprises two peristaltic pumps, which are a first peristaltic pump 5 arranged on the first pipeline 3 and a second peristaltic pump 6 arranged on the second pipeline 4, the two peristaltic pumps can make the first pipeline 3 and the second pipeline 4 have the required pressure for blood flow, the first peristaltic pump 5 is used for pumping blood into the isolated heart 7, and the second peristaltic pump 6 is used for pumping blood back to the recipient animal 2.

[0028] In an embodiment, the detection unit comprises a biopsy device 8, an ultrasonic device 9, a pressure sensor located at the inflow end of the aorta of the isolated heart 7, a blood oxygen monitor, and a blood detection instrument for collecting and detecting perfusion blood, the blood detection instrument is used for continuous collection of perfusion blood, and continuous monitoring of biochemical indicators such as lactic acid, myocardial enzyme spectrum, BNP, etc. of the perfusion blood; the perfusion tank 1 is provided with a biopsy port and an ultrasonic detection port, and the biopsy port and the ultrasonic detection port are each provided with a sealing plug, the sealing plug is opened, and the biopsy device 8 or the ultrasonic device 9 can be inserted into the biopsy port or the ultrasonic detection port respectively, so as to perform biopsy or ultrasonic detection on the isolated heart 7; the ultrasonic device 9 adopts a heart surface ultrasonic probe for checking the structure of the isolated heart 7; the biopsy device 8 can adopt a biopsy forceps for sampling the myocardium.

[0029] In an embodiment, the perfusion tank 1 is provided with a heat preservation layer outside, and the heat preservation layer is connected with a circulating heating device, so as to maintain the inside of the perfusion tank 1 at a set temperature. The pipeline connection unit between the perfusion container and the recipient animal 2 passes through the water bath heating device 10, so that the blood in the pipeline connection unit is heated to a set temperature.

[0030] Blood is drawn from the common carotid artery of a healthy recipient animal 2. The recipient animal 2 acts as a biological oxygenator and metabolic center of the system, its function is to provide oxygen and nutrients to the circulating blood, and metabolize waste. The drawn arterial blood is pumped by a first peristaltic pump 5, the function of the pump is to provide a stable perfusion pressure to deliver oxygenated blood to the isolated heart 7 to be repaired. The blood then flows to the aortic root of the isolated heart 7, perfuses into the coronary artery system of the isolated heart 7 to nourish the myocardium. The venous blood perfused through the heart coronary circulation (coronary artery→coronary sinus→right heart) flows out of the isolated heart 7 and drips to the bottom of the perfusion tank 1. The function of the perfusion tank 1 is to contain the isolated heart 7, collect the backflowing blood and provide a warm environment. The blood collected at the bottom of the tank is then pumped out by a second peristaltic pump 6, the function of the pump is to return the blood to the recipient animal 2. Finally, the blood is returned to the recipient animal 2 through the external jugular vein of the recipient animal 2, completing a complete closed-loop circulation. The connection between the aorta of the isolated heart 7 and the first pipeline 3 is connected to the pressure monitor to maintain the perfusion pressure suitable and stable. The first pipeline 3 and the second pipeline 4 are connected to a three-way valve, which can monitor lactic acid, myocardial enzyme spectrum, etc. at any time. The outer layer of the perfusion tank 1 forms a warm cavity, and the warm cavity is connected to a circulating heating device such as an electric heating wire or an electric heating sheet. The circulating heating device heats water or other heat exchange liquids, and circulates between the heating device and the warm cavity, so that the perfusion tank 1 maintains 37.5°C. The first pipeline 3 and the second pipeline 4 are heated in a 37.5°C water bath device to ensure the temperature of the perfusion blood. At this point, a complete extracorporeal circulation is established. Warm blood perfusion allows myocardial cells to obtain oxygen and nutrients, gradually recover and start to beat again. During the perfusion process, the blood monitoring unit is turned on throughout the process.

[0031] The present application also provides an extracorporeal heart repair method using an extracorporeal heart repair system, as shown in Figure 2 The steps include: The healthy recipient animal 2 is anesthetized, and the common carotid artery and external jugular vein are surgically exposed and cannulated; the aortic root of the isolated heart 7 is connected to the pipeline connection unit; The isolated heart 7 is carefully placed in the perfusion container. Start the first peristaltic pump 5, and the arterial blood of the recipient animal 2 is pumped into the aorta of the isolated heart 7. Due to the blockage of the aortic valve, the blood enters the coronary artery to nourish the myocardium. The metabolized blood flows into the right atrium / ventricle through the coronary sinus, and finally drips to the bottom of the perfusion container from the pulmonary artery or the right atrium.

[0032] The blood at the bottom of the perfusion container is pumped back to the external jugular vein of the recipient animal 2 by the second peristaltic pump 6. At this point, a complete extracorporeal circulation is established, and the blood is heated to a set temperature by water bath during the flow process. Warm blood perfusion allows myocardial cells to obtain oxygen and nutrients, gradually recover and start to beat again (recover electrical and mechanical activity).

[0033] During perfusion, the monitoring unit is turned on throughout the whole process: the perfusion pressure is ensured to be within a safe range (e.g. 60-80 mmHg) by a pressure sensor. The myocardial oxygen metabolic rate is evaluated by arteriovenous oxygen difference. Blood is periodically drawn from the sampling port for testing of lactic acid level (lactic acid clearance rate is a key indicator for evaluating the recovery of cardiac metabolic function). The heart beating condition is observed in real time by epicardial ultrasound, and cardiac function parameters are measured. If necessary, a biopsy is taken through the biopsy port for rapid pathological examination.

[0034] According to the comprehensive evaluation of the above-mentioned multiple indicators, it is judged whether the isolated heart 7 recovers well in function, so as to decide whether it can be used for transplantation.

[0035] Since the present application integrates epicardial ultrasound and biopsy, real-time imaging functional data and histological samples of the heart can be directly obtained during perfusion, providing a more solid and objective basis for transplantation decision-making, thereby reducing the risk of transplantation failure caused by the use of marginal donor hearts. The present application uses the recipient animal 2 itself as a natural biological pump and oxygenator, eliminating the need for expensive and complex mechanical blood pumps, oxygenators, heaters and related control systems in traditional mechanical perfusion systems. The technical solution only uses a standard peristaltic pump connected to the recipient animal 2, which directly leads to the simplification of the system structure and a significant reduction in manufacturing cost, making the technology more easily applied in clinical medical institutions. Unlike the use of artificial perfusion fluid, the present application uses whole blood of the recipient animal 2 for perfusion, which contains various cells, hormones, nutrients and buffer systems, providing a more physiological internal environment. The technical solution is beneficial to the more effective repair and recovery of myocardial cells from thermal ischemic injury, improving the quality of recovery of the donor heart.

[0036] The principles and implementation modes of the present application are described by applying specific examples in the present application. The above examples are only used to help understand the method of the present application and its core idea; at the same time, for those skilled in the art, according to the idea of the present application, there will be changes in specific implementation modes and application scope. In summary, the content of the present specification should not be understood as a limitation of the present application.

Claims

1. An extracorporeal heart repair system, characterized by: The application relates to a perfusion container for containing and connecting a perfused isolated heart, a pipeline connecting unit for connecting the perfusion container with the common carotid artery and the external jugular vein of a recipient animal respectively to form a complete extracorporeal circulation loop, a circulation power unit arranged on the pipeline connecting unit for driving blood circulation between the isolated heart in the perfusion container and the recipient animal, and a detection unit for detecting the isolated heart and determining the state of the isolated heart according to the detection result. The perfusion container comprises a perfusion tank capable of being arranged in a sealed mode, the perfusion tank is used for containing the isolated heart, an inlet is arranged at the top of the perfusion tank, an outlet is arranged at the bottom of the perfusion tank, sealing devices are arranged at the inlet and the outlet, the common carotid artery of the recipient animal is communicated with the aorta of the isolated heart through the pipeline connecting unit arranged in the inlet, and the external jugular vein of the recipient animal is communicated with the outlet. The pipeline connecting unit comprises a first pipeline and a second pipeline, one end of the first pipeline is communicated with the common carotid artery of the recipient animal, the other end of the first pipeline passes through the inlet and is communicated with the aorta of the isolated heart, one end of the second pipeline is communicated with the external jugular vein of the recipient animal, and the other end of the second pipeline is communicated with the outlet. The circulation power unit comprises peristaltic pumps, and at least two peristaltic pumps are arranged on the pipeline connecting unit. The detection unit comprises a biopsy device and an ultrasonic device, biopsy ports and ultrasonic detection ports are arranged on the perfusion tank, sealing plugs are arranged at the biopsy ports and the ultrasonic detection ports, the sealing plugs are opened to respectively introduce the biopsy device or the ultrasonic device to perform biopsy or ultrasonic detection on the isolated heart. The detection unit further comprises a pressure sensor and a blood oxygen monitor arranged at the inflow end of the aorta of the isolated heart, and a blood detection instrument for collecting and detecting perfusion blood.

2. The extracorporeal heart repair system of claim 1, wherein: An insulation layer is arranged on the outer layer of the perfusion tank, a circulating heating device is arranged outside the insulation layer, and the inside of the perfusion tank can be maintained at a set temperature.

3. The extracorporeal heart repair system of claim 2, wherein: A water bath heating device is further arranged, the pipeline connecting unit between the perfusion container and the recipient animal passes through the water bath heating device, so that the blood in the pipeline connecting unit is heated to a set temperature.

4. The extracorporeal heart repair system of claim 1, wherein: A perfusion cover is sealingly connected to the top of the perfusion tank, the inlet, the biopsy port and the ultrasonic detection port are arranged on the perfusion cover, and the perfusion tank is made of medical transparent material.

5. The extracorporeal heart repair system of claim 2, wherein: The application further discloses a perfusion method comprising the following steps:

6. The extracorporeal heart repair system of claim 5, wherein: Anesthesia is performed on a healthy recipient animal, the common carotid artery and the external jugular vein of the recipient animal are exposed and cannulated through surgery, and the aortic root of the isolated heart is connected with the pipeline connecting unit; 7. The extracorporeal heart repair system of claim 2, wherein: The isolated heart is placed in the perfusion container, the circulation power unit is started, the arterial blood of the recipient animal is pumped into the aorta of the isolated heart, and finally dripped from the pulmonary artery or the right atrium to the bottom of the perfusion container; 8. The extracorporeal heart repair system of claim 1, wherein: The blood at the bottom of the perfusion container is pumped back to the external jugular vein of the recipient animal through the outlet; 9. The extracorporeal heart repair system of claim 5, wherein: During the perfusion process, the detection unit is started, the function recovery state of the isolated heart is judged according to the comprehensive evaluation of the detection indexes, and whether the isolated heart can be used for transplantation is determined.

10. An extracorporeal heart repair method using the extracorporeal heart repair system according to any one of claims 1 to 9, characterized by: ​ ​ ​ ​ ​

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