BackgroundCardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects.Methods and ResultsUsing a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω‐nitro‐L‐arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω‐nitro‐L‐arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω‐nitro‐L‐arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels.ConclusionsHOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.

中文翻译：

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低温氧合灌注通过保留循环死亡后捐赠的心脏移植物中内皮一氧化氮的产生来改善血管和收缩功能

背景循环死亡后的心脏捐赠是增加移植物可用性的一个有前途的选择。与目前的临床标准冷静态保存相比，在常温机器灌注之前进行 30 分钟低温氧合灌注 (HOPE) 保存移植物可能会改善心脏恢复。我们研究了 HOPE 期间保留的一氧化氮合酶活性对其有益效果的作用。方法和结果使用循环死亡后捐献的大鼠模型，心脏经历原位缺血（21 分钟），并被移出冷藏期（30 分钟） ，然后在常温条件下（60 分钟）以左心室负荷进行再灌注。比较了三种冷藏条件：静态冷藏、HOPE 和含有 Nω-硝基-L-精氨酸甲酯（一氧化氮合酶抑制剂）的 HOPE。为了评估 HOPE 心脏早期再灌注期间高冠脉流量的潜在混杂效应，在另外 2 组（冷静态储存和含 Nω-硝基-L-精氨酸甲酯的 HOPE）中施用缓激肽以使冠脉流量正常化至 HOPE 水平。根据心输出量、左心室做功、收缩和舒张率以及冠脉流量测定，HOPE 与冷静态储存心脏的心脏恢复显着改善（P <0.05）。此外，HOPE 还可减轻再灌注后钙超载。引人注目的是，即使早期再灌注冠脉流量正常化至 HOPE 水平，在 HOPE 期间添加 Nω-硝基-L-精氨酸甲酯在很大程度上消除了其有益作用。结论与当前的临床标准相比，HOPE 可以更好地保留心室和血管功能。重要的是，HOPE 的有益效果需要在冷藏期间保持一氧化氮合酶活性。因此，在常温机器灌注之前应用 HOPE 是优化循环死亡心脏移植后捐赠移植物恢复的一种有前途的方法。