BACKGROUND

Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts undergo potentially deleterious warm ischemia/reperfusion (I/R). As endothelial damage is a key factor in cardiac I/R injury, we aimed to investigate the tolerance of cardiac and endothelial function after various durations of warm ischemia to improve the timing and choice of cardioprotective therapies.

METHODS

Isolated, working rat hearts were perfused for 20 minutes aerobically, then underwent various periods of warm global ischemia and either 30 or 60 minutes of reperfusion.

RESULTS

Compared with non-ischemic hearts, recovery of left ventricular work (heart rate–developed pressure product) was significantly reduced at 60 minutes of reperfusion with ≥27 minutes of ischemia (p <0.05 for all), but was unchanged after 21 or 24 minutes of ischemia. Markers of cell death and edema significantly increased with ≥27-minute ischemia compared with non-ischemic hearts (p <0.05 for all). Endothelial-dependent vasodilation was significantly impaired compared with non-ischemic hearts with ≥24 minutes of ischemia, whereas endothelial-independent vasodilation was impaired with ≥27 minutes of ischemia (p <0.05 for all). Furthermore, with ≥24 minutes of ischemia, superoxide production by nitric oxide synthase and peroxynitrite levels were significantly increased compared with non-ischemic hearts, suggesting endothelial nitric oxide synthase (eNOS) uncoupling (p <0.05 for both).

CONCLUSIONS

The first signs of endothelial dysfunction after cardiac ischemia occur with less ischemia than cardiac functional alterations, and may result from increased eNOS uncoupling. Strategies aimed at improving eNOS coupling may thus help to optimize both endothelial and myocardial recovery, ultimately facilitating DCD heart transplantation.

中文翻译：

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缺血/再灌注对循环系统死亡后供血中内皮功能和收缩力的不同作用。

背景

循环死亡后的捐赠（DCD）可以显着改善心脏移植物的利用率。但是，DCD心脏可能会遭受有害的温暖缺血/再灌注（I / R）。由于内皮损伤是心脏I / R损伤的关键因素，我们的目的是研究各种持续时间的热缺血后心脏和内皮功能的耐受性，以改善心脏保护疗法的时机和选择。

方法

离体的正常大鼠心脏需氧灌注20分钟，然后经历不同时期的温暖的整体缺血和30或60分钟的再灌注。

结果

与非缺血性心脏相比，缺血性≥27分钟的再灌注60分钟时左心室工作的恢复（心率产生的压力积）显着降低（所有p <0.05），但在21或24分钟后未改变缺血。与非缺血性心脏相比，缺血性≥27分钟时，细胞死亡和水肿的标志物显着增加（所有p均<0.05）。与缺血≥24分钟的非缺血性心脏相比，内皮依赖性血管舒张明显受损，而缺血≥27分钟的非内皮依赖性血管舒张则受损（p均<0.05）。此外，在≥24分钟的缺血中，与非缺血性心脏相比，一氧化氮合酶和过氧化亚硝酸盐产生的超氧化物水平显着增加，提示内皮型一氧化氮合酶（eNOS）解偶联（两者均p <0.05）。

结论

与心脏功能改变相比，心脏缺血后出现内皮功能障碍的最初征象发生的缺血更少，这可能是由于eNOS解偶联增加所致。因此，旨在改善eNOS偶联的策略可能有助于优化内皮和心肌的恢复，最终促进DCD心脏移植。