Donor heart myocardial protection system and method
By constructing a low-temperature thermal buffer environment that includes heart containment, thermal buffer isolation, and an external low-temperature unit, the problem of damage caused by temperature gradients during the cold preservation of donor hearts was solved, achieving good protection and functional recovery of the myocardium.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHONGSHAN HOSPITAL FUDAN UNIV
- Filing Date
- 2026-03-04
- Publication Date
- 2026-05-05
AI Technical Summary
Existing cryopreservation techniques fail to effectively control the temperature gradient between different parts of the donor heart, leading to localized overcooling or freezing, causing myocardial damage and affecting functional recovery after cardiac resuscitation.
A uniform and stable low-temperature thermal buffer environment is constructed by using a heart-containing unit, a thermal buffer isolation unit, and an external low-temperature unit. The temperature gradient is reduced by suspending and low-temperature buffering media, and temperature changes are monitored in real time by a temperature monitoring unit.
It effectively reduces the temperature gradient in different parts of the donor heart, reduces myocardial damage related to cold preservation, improves the functional recovery effect after cardiac resuscitation, and prolongs the cold preservation time.
Smart Images
Figure CN121970745A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of heart transplantation and organ preservation technology, and more specifically, it relates to a donor heart myocardial protection system and method. Background Technology
[0002] Cold preservation of donor hearts is one of the most commonly used organ preservation methods in heart transplantation. Its basic principle is to delay ischemic damage by reducing the metabolic level of the myocardium. Traditional cold preservation methods usually involve perfusing the donor heart with a heart preservation solution (such as HTK, UW, etc.) after heart arrest, placing the heart in a low-temperature environment for preservation, and maintaining the low temperature during transportation.
[0003] Current cryopreservation technologies generally focus on target temperature ranges; for example, it is generally believed that maintaining the donor heart at approximately 4-8°C helps protect the myocardium. However, in actual clinical procedures and transport, the donor heart is often cooled using ice or an ice-water mixture, making it difficult to precisely control the temperature distribution in different areas of its interior and surface, often resulting in significant spatial temperature gradients and temporal temperature fluctuations.
[0004] During cryopreservation, localized areas of the donor heart may experience overcooling, freezing, or rapid temperature changes due to direct contact with ice sources or uneven cooling. This can induce localized myocardial cold injury, mitochondrial dysfunction, and calcium homeostasis disorders, ultimately affecting functional recovery after cardiac resuscitation. Current technologies generally neglect the impact of temperature distribution (especially temperature uniformity and temperature gradient) on myocardial protection during cryopreservation and lack a systematic solution to this problem.
[0005] Therefore, there is an urgent need for a new cryopreservation myocardial protection technology that can reduce temperature gradients and local cold damage by regulating the temperature distribution of the donor heart during cryopreservation, thereby improving the protective effect of the donor heart under long-term cryopreservation conditions. Summary of the Invention
[0006] The purpose of this invention is to address the technical problems existing in cryopreservation technology, namely that existing cryopreservation methods mainly focus on the overall low temperature environment and fail to effectively control the temperature gradient between different parts of the donor heart; that local areas of the donor heart are prone to overcooling or freezing during cryopreservation, leading to cryopreservation-related myocardial damage; and that existing methods are difficult to stably achieve good protection of myocardial structure and function under long-term cryopreservation conditions.
[0007] To achieve the above-mentioned objectives, this application provides a method and system for myocardial protection of donor hearts, which reduces the temperature gradient of the donor heart in the spatial and temporal dimensions by constructing a uniform and stable low-temperature thermal buffer environment under cold preservation conditions, thereby reducing myocardial damage related to cold preservation and improving the functional recovery effect of the donor heart after resuscitation.
[0008] In a first aspect, this application provides a donor heart myocardial protection system, comprising:
[0009] A heart containment unit for containing a donor heart and a heart preservation solution, and for suspending the donor heart in the heart preservation solution; A thermal buffer isolation unit is used to house the heart housing unit. A low-temperature buffer medium is provided inside the unit, and the heart housing unit is separated from the inner wall of the thermal buffer isolation unit by the low-temperature buffer medium. An external cryogenic unit is used to house the thermal buffer isolation unit and provide an external cryogenic environment.
[0010] Furthermore, both the heart-containing unit and the thermal buffer isolation unit are medical-grade sealed containers.
[0011] Furthermore, the low-temperature buffer medium is crushed ice, an ice-water mixture, or a low-temperature phase change material.
[0012] Furthermore, the heart receiving unit is provided with a suspension assembly for supporting the donor heart and suspending the donor heart in the heart preservation fluid.
[0013] Furthermore, the suspension component is a flexible mesh structure or a multi-point flexible support structure.
[0014] Furthermore, the system also includes a temperature monitoring unit, which includes a temperature sensor disposed in the donor heart, the heart preservation fluid, and / or the cryogenic buffer medium.
[0015] Secondly, this application provides a method for myocardial protection of a donor heart using the aforementioned donor heart myocardial protection system, comprising the following steps: Step 1: Place the donor heart, which has been perfused with preservation fluid, into the heart holding unit and inject heart preservation fluid to completely suspend it; Step 2: Place the heart-containing unit with the donor heart suspended in it into the thermal buffer isolation unit, and fill the heart-containing unit with a low-temperature buffer medium. Step 3: Place the thermal buffer isolation unit filled with low-temperature buffer medium into the external low-temperature unit for cold storage.
[0016] Furthermore, the method also includes a step of monitoring the temperature of the donor heart, heart preservation fluid, and / or cryogenic buffer medium via a temperature monitoring unit during the cold preservation process to detect temperature changes.
[0017] Thirdly, this application provides the use of the aforementioned donor heart myocardial protection system, or the aforementioned donor heart cryopreservation method, in the preparation of donor heart myocardial protection products.
[0018] In summary, compared with the prior art, this application has the following beneficial effects: 1. Reduce temperature gradient: Through suspension and thermal buffering mechanisms, the spatial temperature gradient between different parts of the donor heart is effectively reduced, avoiding local overcooling or freezing.
[0019] 2. Improves myocardial protection: Even in near-freezing temperatures, it can still provide good protection for the donor heart's structure and function, significantly improving myocardial function after resuscitation.
[0020] 3. Extended cryopreservation time: Long-term cryopreservation of donor hearts can be achieved without the need for a complex mechanical perfusion system, which has good prospects for clinical application.
[0021] 4. The method of this application is simple and highly scalable: the method is based on the principle of passive thermodynamics, does not rely on complex equipment, and is easy to promote and apply in the existing clinical cold preservation process. Attached Figure Description
[0022] Figure 1 : Top view of the donor heart myocardial protection system in Embodiment 1 of this application.
[0023] Figure 2 In Embodiment 1 of this application, a schematic diagram of the suspension component is shown to highlight its structure.
[0024] Figure 3 In Embodiment 2 of this application, a schematic diagram of the suspension component is shown to highlight its structure.
[0025] Figure 4 Comparison of systolic and diastolic function indices of porcine donor hearts under different cryopreservation methods.
[0026] Reference numerals: 1. Heart housing unit; 2. Suspension assembly; 3. Thermal buffer isolation unit; 4. External cryogenic unit; 5. Housing; 6. First limiting step; 7. Second limiting step. Detailed Implementation
[0027] The technical solutions and effects of this application will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely for explaining the invention and are not intended to limit the invention.
[0028] Example 1 This embodiment discloses a donor heart myocardial protection system, which includes: a heart housing unit 1, a thermal buffer isolation unit 3, and an external cryogenic unit 4.
[0029] The heart-containing unit 1 is used to contain the donor heart and heart preservation fluid, suspending the donor heart in the preservation fluid. In this embodiment, the heart-containing unit 1 is a medical sealed container, which can be a sterile medical bag. A suspension component 2 is installed inside the sterile bag. The suspension component 2 is a flexible mesh structure made of medical-grade silicone. The mesh structure is symmetrically fixed to the middle of the inner wall of the sterile bag by multiple flexible silicone ropes. The length of the silicone ropes can be adjusted according to actual needs to ensure that the donor heart can suspend in the middle of the sterile bag after being placed inside, without contacting the inner wall of the sterile bag. During use, heart preservation fluid, such as HTK preservation fluid, is added to the sterile bag to completely suspend the donor heart in the preservation fluid.
[0030] The thermal buffer isolation unit 3 is used to house the heart receiving unit 1. In this embodiment, the thermal buffer isolation unit 3 is also a medical sealed container, which can be a medical sterile bag. The inner diameter of the thermal buffer isolation unit 3 is larger than the outer diameter of the heart receiving unit 1, with a certain gap reserved between them for filling with a low-temperature buffer medium. The low-temperature buffer medium can be crushed ice, an ice-water mixture, or a low-temperature phase change material. The heart receiving unit 1 and the inner wall of the thermal buffer isolation unit 3 are separated by the low-temperature buffer medium to achieve a thermal buffer isolation effect.
[0031] A positioning and fitting assembly is provided between the heart receiving unit 1 and the thermal buffer isolation unit 3. The positioning and fitting assembly includes a first limiting step 6 provided on the outer wall of the heart receiving unit 1 and a second limiting step 7 provided on the inner wall of the thermal buffer isolation unit 3. In this embodiment, the first limiting step 6 is an annular protrusion structure, and the second limiting step 7 is another annular protrusion structure that abuts against the first limiting step 6. The two abut against each other to form a limiting fit, thereby positioning the heart receiving unit 1 within the thermal buffer isolation unit 3 and preventing the heart receiving unit 1 from shaking or shifting during transportation.
[0032] The external low-temperature unit 4 is used to house the heat buffer isolation unit 3 and provide an external low-temperature environment. In this embodiment, a medical low-temperature refrigerator can be used.
[0033] It is also provided with a housing 5 to house the external low-temperature unit 4, which is embedded in the housing 5.
[0034] Example 2 This embodiment discloses a donor heart myocardial protection system. Unlike Embodiment 1, in this embodiment, the suspension component 2 is a multi-point flexible support structure. This structure consists of multiple independent flexible support strips, which can be made of medical-grade silicone. The multiple independent flexible support strips correspond to the apex of the heart and both sides of the heart, respectively, to further limit the displacement of the heart under transport vibration and tilting conditions. This also keeps the donor heart suspended in the heart preservation fluid, avoiding direct contact with the container wall.
[0035] Example 3 This embodiment discloses a donor heart myocardial protection system. Unlike Embodiment 1, this system further includes a temperature monitoring unit. This unit comprises three medical temperature sensors, respectively positioned at the apex of the donor heart, in the heart preservation fluid of the heart-containing unit 1, and in the low-temperature buffer medium of the thermal buffer isolation unit 3. The temperature sensors are connected to a display outside the refrigerator via wires, allowing real-time display of temperature data at each monitoring point, facilitating operators' monitoring of temperature changes.
[0036] Example 4 This embodiment discloses a method for myocardial protection of a donor heart using the donor heart myocardial protection system described in Embodiment 1, comprising the following steps: Step 1: Place the donor heart, which has been perfused with preservation fluid, into the heart holding unit and inject heart preservation fluid to completely suspend it; Step 2: Place the heart-containing unit with the donor heart suspended in it into the thermal buffer isolation unit, and fill the heart-containing unit with a low-temperature buffer medium. Step 3: Place the thermal buffer isolation unit filled with low-temperature buffer medium into the external low-temperature unit for cold storage.
[0037] This embodiment uses the cold preservation and resuscitation of a pig donor heart as an example to illustrate the process. Specifically: 1. Before obtaining the heart, the pig donor heart was perfused with 1L of HTK preservation solution to stop the beating. 2. After the procedure, 2L of HTK preservation solution was used for supplemental perfusion, the same as the clinical human donor heart protocol. 3. Place the donor heart in the heart receiving unit (first medical sterile bag), and use the suspension component to completely suspend the donor heart in HTK preservation solution; 4. Place the heart receiving unit into the heat buffer isolation unit (second medical sterile bag), and fill the heart receiving unit with a low temperature buffer medium (ice-water mixture) to separate the heart receiving unit from the inner wall of the heat buffer isolation unit. 5. Place the heat buffer isolation unit in an external low-temperature unit (medical low-temperature refrigerator) for cold preservation.
[0038] Tests showed that the cold preservation time could reach about 20 hours; after the cold preservation was completed, the donor heart was resuscitated using the Lagendorf system, and the results showed that the heart resuscitated well and the myocardial structure and function remained intact.
[0039] This embodiment demonstrates that, through liquid suspension and low-temperature thermal buffering, effective myocardial protection of the donor heart can still be achieved in a near-freezing cold storage environment.
[0040] Example 5 The method described in Example 4 was used to cryopreserve hearts from different pig donors, and cardiac function was tested. The results are shown in Table 1 and... Figure 1 As shown.
[0041] Table 1. Max dp / dt and Min dp / dt under the traditional method (10h) and the improved method (20h, 22h)
[0042] The results of the examples show that, compared with the traditional preservation method (preservation time of approximately 10 hours), the improved heart preservation method can significantly extend the preservation time of porcine donor hearts (20–22 hours), and the overall myocardial contractile and diastolic functions are significantly improved. Using the rate of change of left ventricular pressure (dp / dt) as an indicator of cardiac function, both the Max dp / dt and Min dp / dt under the improved method show an overall increase (increased absolute value) compared to the traditional method, indicating enhanced myocardial contractility and diastolic capacity. Although no statistically significant difference was found between the 22-hour preservation group and the 10-hour preservation group in some comparisons (P>0.05), all indicators showed an improvement trend superior to the traditional method; further analysis showed that at a preservation time of approximately 20 hours, the dp / dt index under the improved method was significantly improved compared to the 10-hour group. These results demonstrate that the preservation method described in this invention can effectively maintain and improve myocardial mechanical properties while extending the usable time of donor hearts, providing a reliable technical solution for long-term donor heart preservation.
[0043] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.
Claims
1. A donor heart myocardial protection system, characterized in that, include: A heart containment unit for containing a donor heart and a heart preservation solution, and for suspending the donor heart in the heart preservation solution; A thermal buffer isolation unit is used to house the heart housing unit. A low-temperature buffer medium is provided inside the unit, and the heart housing unit is separated from the inner wall of the thermal buffer isolation unit by the low-temperature buffer medium. An external cryogenic unit is used to house the thermal buffer isolation unit and provide an external cryogenic environment.
2. The donor heart myocardial protection system according to claim 1, characterized in that, Both the heart-containing unit and the thermal buffer isolation unit are medical-grade sealed containers.
3. The donor heart myocardial protection system according to claim 1, characterized in that, The low-temperature buffer medium is crushed ice, an ice-water mixture, or a low-temperature phase change material.
4. The donor heart myocardial protection system according to claim 1, characterized in that, The heart receiving unit is provided with a suspension assembly, which is used to support the donor heart and suspend the donor heart in the heart preservation fluid.
5. The donor heart myocardial protection system according to claim 4, characterized in that, The suspension component is a flexible mesh structure or a multi-point flexible support structure.
6. The donor heart myocardial protection system according to claim 1, characterized in that, The system also includes a temperature monitoring unit, which includes a temperature sensor disposed in the donor heart, the heart preservation fluid, and / or the cryogenic buffer medium.
7. A method for myocardial protection of a donor heart using the donor heart myocardial protection system as described in any one of claims 1-6, characterized in that, Includes the following steps: Step 1: Place the donor heart, which has been perfused with preservation fluid, into the heart holding unit and inject heart preservation fluid to completely suspend it; Step 2: Place the heart-containing unit with the donor heart suspended in it into the thermal buffer isolation unit, and fill the heart-containing unit with a low-temperature buffer medium. Step 3: Place the thermal buffer isolation unit filled with low-temperature buffer medium into the external low-temperature unit for cold storage.
8. The method for myocardial protection of donor hearts according to claim 7, characterized in that, The method further includes a step of monitoring the temperature of the donor heart, heart preservation fluid, and / or cryogenic buffer medium via a temperature monitoring unit during cold preservation to detect temperature changes.
9. Use of the donor heart myocardial protection system according to any one of claims 1-6, or the donor heart cryopreservation method according to any one of claims 7-8, in the preparation of donor heart myocardial protection products.