Egle Manuel, Segiser Adrian, Clavier Alexia, Beer Georgia, Helmer Anja, Ottersberg Rahel, Graf Selianne, Arnold Maria, Zulauf Fabio, Lagger Deborah, Bartkevics Maris, Kadner Alexander, Krummenacher Daja, Vermathen Peter, Siepe Matthias, Longnus Sarah
Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.
Eur J Cardiothorac Surg. 2025 Mar 4;67(3). doi: 10.1093/ejcts/ezaf061.
Donation after circulatory death provides excellent patient outcomes in heart transplantation; however, warm ischaemic graft damage remains a concern. We have reported that a brief period of hypothermic oxygenated perfusion prior to normothermic reperfusion improves graft recovery in a rat model. Here, we investigated the cardioprotective benefits and mechanisms of this approach compared to the current clinical standard in a large animal model.
Circulatory death was induced in anaesthetized male Schweizer Edelschwein pigs (55 kg). Hearts underwent 20 min of warm, in-situ ischaemia, followed by a cold coronary flush and explantation. After 15 min backtable preparation, hearts underwent either 15 min cold static storage (control) or 30 min hypothermic oxygenated perfusion. All hearts were perfused ex vivo under normothermic conditions; 3 h in an unloaded mode, followed by 1 h with left ventricular loading to assess cardiac recovery.
Compared to control conditions (n = 5), hypothermic oxygenated perfusion (n = 5) increased recovery of left ventricular function (cardiac output and maximum relaxation rate, P < 0.001 for both) and decreased cell death marker release (heart-type fatty acid binding protein, P = 0.009 and myoglobin, P < 0.001). In parallel, hypothermic oxygenated perfusion reduced the release of succinate and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine.
A brief period of hypothermic oxygenated perfusion, applied as a reperfusion therapy between graft procurement and normothermic machine perfusion, provides cardioprotection in a porcine model of donation after circulatory death. Hypothermic oxygenated perfusion is a promising, easily applicable, cardioprotective reperfusion strategy; this study provides key evidence to support clinical translation.
心脏移植中循环性死亡后捐献可带来良好的患者预后；然而，热缺血性移植物损伤仍是一个问题。我们曾报道，在常温再灌注前进行一段短时间的低温氧合灌注可改善大鼠模型中的移植物恢复情况。在此，我们在大型动物模型中研究了该方法与当前临床标准相比的心脏保护益处及机制。
对麻醉后的雄性施韦泽小型猪（55千克）诱导循环性死亡。心脏经历20分钟的原位热缺血，随后进行冷冠状动脉冲洗并取出。在15分钟的后台准备后，心脏要么进行15分钟的冷静态保存（对照组），要么进行30分钟的低温氧合灌注。所有心脏在常温条件下进行体外灌注；无负荷模式下灌注3小时，随后左心室加载1小时以评估心脏恢复情况。
与对照条件（n = 5）相比，低温氧合灌注（n = 5）提高了左心室功能的恢复（心输出量和最大舒张速率，两者P均<0.001），并减少了细胞死亡标志物的释放（心脏型脂肪酸结合蛋白，P = 0.009；肌红蛋白，P <0.001）。同时，低温氧合灌注减少了琥珀酸的释放以及氧化应激标志物8 - 羟基 - 2'-脱氧鸟苷的释放。
在移植物获取与常温机器灌注之间应用一段短时间的低温氧合灌注作为再灌注疗法，可在循环性死亡后捐献的猪模型中提供心脏保护。低温氧合灌注是一种有前景、易于应用的心脏保护再灌注策略；本研究提供了支持临床转化的关键证据。
