INSERM, U886-Cardioprotection, Lyon, France.
J Cardiovasc Pharmacol Ther. 2011 Jun;16(2):117-30. doi: 10.1177/1074248410383174. Epub 2010 Oct 11.
Infarct size is determined not only by the severity of ischemia but also by pathological processes initiated at reperfusion. Accumulating experimental evidence indicates that lethal reperfusion injury might account for up to half of the final size of the myocardial infarct. Ischemic postconditioning (brief repeated periods of ischemia-reperfusion applied at the onset of coronary reflow) has been recently described as a powerful cardioprotection mechanism that prevents lethal reperfusion injury. This is the first method proven to reduce the final infarct size by about 50% in several in vivo models and to be confirmed in recent preliminary human studies. The molecular pathways are incompletely mapped but they probably converge to a mitochondrial key target: the mitochondrial permeability transition pore (PTP) which opening during early reperfusion is an event that promotes myocardial cell death. In different animal models and experimental settings, pharmacological PTP inhibition at the onset of reperfusion reproduces all the cardioprotective effects of ischemic postconditioning. In a recent proof-of-concept trial, the administration (just before percutaneous coronary intervention) of cyclosporine A, a potent PTP inhibitor, was associated with smaller infarct size. This review will focus on the physiological preclinical data on both ischemic and pharmacological postconditioning that are relevant to their translation to clinical therapeutics.
梗死面积不仅取决于缺血的严重程度，还取决于再灌注时启动的病理过程。越来越多的实验证据表明，致命的再灌注损伤可能占心肌梗死最终面积的一半。缺血后处理（在冠状动脉再灌注开始时短暂重复的缺血-再灌注期）最近被描述为一种强大的心脏保护机制，可以防止致命的再灌注损伤。这是第一种被证明可以在几种体内模型中减少约 50%的最终梗死面积，并在最近的初步人体研究中得到证实的方法。分子途径尚未完全阐明，但它们可能汇聚到一个线粒体关键靶点：线粒体通透性转换孔（PTP），其在再灌注早期开放是促进心肌细胞死亡的事件。在不同的动物模型和实验环境中，在再灌注开始时应用药理学 PTP 抑制剂可复制缺血后处理的所有心脏保护作用。在最近的一项概念验证试验中，在经皮冠状动脉介入治疗之前给予环孢素 A（一种有效的 PTP 抑制剂）可使梗死面积减小。这篇综述将重点介绍缺血后处理和药理学后处理的生理临床前数据，这些数据与它们向临床治疗的转化有关。
