Background

Use of cardiac grafts obtained with donation after circulatory death (DCD) could significantly improve donor heart availability. As DCD hearts undergo potentially deleterious warm ischemia and reperfusion, clinical protocols require optimization to ensure graft quality. Thus, we investigated effects of alternative preservation conditions on endothelial and/or vascular and contractile function in comparison with the current clinical standard.

Methods

Using a rat DCD model, we compared currently used graft preservation conditions, St. Thomas n°2 (St. T) at 4°C, with potentially more suitable conditions for DCD hearts, adenosine-lidocaine preservation solution (A-L) at 4°C or 22°C. Following general anesthesia and diaphragm transection, hearts underwent either 0 or 18 min of in-situ warm ischemia, were explanted, flushed and stored for 15 min with either St. T at 4°C or A-L at 4°C or 22°C, and then reperfused under normothermic, aerobic conditions. Endothelial integrity and contractile function were determined.

Results

Compared to 4°C preservation, 22°C A-L significantly increased endothelial nitric oxide synthase (eNOS) dimerization and reduced oxidative tissue damage (p < 0.05 for all). Furthermore, A-L at 22°C better preserved the endothelial glycocalyx and coronary flow compared with St. T, tended to reduce tissue calcium overload, and stimulated pro-survival signaling. No significant differences were observed in cardiac function among ischemic groups.

Conclusions

Twenty-two-degree Celsius A-L solution better preserves the coronary endothelium compared to 4°C St. T, which likely results from greater eNOS dimerization, reduced oxidative stress, and activation of the reperfusion injury salvage kinase (RISK) pathway. Improving heart preservation conditions immediately following warm ischemia constitutes a promising approach for the optimization of clinical protocols in DCD heart transplantation.

中文翻译：

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移植物保存条件对循环死亡后捐献大鼠模型冠状动脉内皮及心脏功能恢复的影响

背景

使用在循环死亡（DCD）后捐赠获得的心脏移植物可以显着提高捐赠心脏的可用性。由于 DCD 心脏经历潜在有害的热缺血和再灌注，临床方案需要优化以确保移植质量。因此，我们研究了与当前临床标准相比，替代保存条件对内皮和/或血管和收缩功能的影响。

方法

使用大鼠 DCD 模型，我们比较了目前使用的移植物保存条件，即 4°C 的 St. Thomas n°2 (St. T)，以及可能更适合 DCD 心脏的条件，4° 的腺苷-利多卡因保存液 (AL)摄氏度或 22°C。在全身麻醉和横膈膜横断后，心脏接受 0 或 18 分钟的原位热缺血，取出，冲洗并用 4°C 的 St.T 或 4°C 或 22°C 的 AL 储存 15 分钟，然后在常温、有氧条件下再灌注。测定内皮完整性和收缩功能。

结果

与 4°C 保存相比，22°C AL 显着增加内皮一氧化氮合酶 (eNOS) 二聚化并减少氧化组织损伤（所有p < 0.05）。此外，与 St. T 相比，22°C 的 AL 更好地保留了内皮糖萼和冠状动脉血流，倾向于减少组织钙超载，并刺激促生存信号。缺血组间心功能无显着差异。

结论

与 4°C St. T 相比，22 摄氏度的 AL 溶液更好地保护了冠状动脉内皮，这可能是由于更大的 eNOS 二聚化、减少的氧化应激和再灌注损伤补救激酶 (RISK) 途径的激活。在热缺血后立即改善心脏保存条件是优化 DCD 心脏移植临床方案的有希望的方法。