Hausenloy Derek J
The Hatter Cardiovascular Institute, University College London Hospital and Medical School, London, United Kingdom.
Thromb Haemost. 2009 Apr;101(4):626-34.
Coronary heart disease (CHD) is the leading cause of death globally. Following an acute coronary artery occlusion, timely myocardial reperfusion using either primary percutaneous coronary intervention (PCI) or thrombolytic therapy remains the most effective treatment strategy for reducing myocardial infarct size, preventing left ventricular remodelling, preserving left ventricular systolic function and improving clinical outcomes. However, the full benefits of myocardial reperfusion are not realised, given that the actual process of reperfusing ischaemic myocardium can independently induce cell death - a phenomenon termed lethal reperfusion injury. Ischaemic postconditioning represents an innovative treatment strategy for limiting lethal myocardial reperfusion injury and further reducing myocardial infarct size for those patients undergoing primary PCI. It is achieved by interrupting the normal myocardial reperfusion process, with several intermittent episodes of coronary myocardial ischaemia induced by low-pressure inflations of the angioplasty balloon in the infarct-related coronary artery. Experimental studies demonstrate that this stuttered form of myocardial reperfusion improves myocardial perfusion, maintains endothelial function, attenuates apoptotic cell death, reduces myocardial infarct size, preserves left ventricular systolic function and reduces mortality. The mechanisms underlying the cardioprotective effect of ischaemic postconditioning are the subject of intense investigation. In this article we review the signalling pathways which have been implicated as potential mediators of ischaemic postconditioning, the identification of which have provided novel pharmacological targets of cardioprotection capable of recapitulating the protective benefits of ischaemic postconditioning.
冠心病（CHD）是全球主要的死亡原因。急性冠状动脉闭塞后，采用直接经皮冠状动脉介入治疗（PCI）或溶栓治疗进行及时的心肌再灌注，仍然是减少心肌梗死面积、预防左心室重构、维持左心室收缩功能及改善临床结局的最有效治疗策略。然而，心肌再灌注的全部益处并未实现，因为对缺血心肌进行再灌注的实际过程可独立诱导细胞死亡——这一现象被称为致死性再灌注损伤。缺血后适应是一种创新性治疗策略，用于限制致死性心肌再灌注损伤，并进一步缩小接受直接PCI患者的心肌梗死面积。它通过中断正常的心肌再灌注过程来实现，即通过梗死相关冠状动脉内血管成形术球囊的低压充气诱导数次间歇性冠状动脉心肌缺血。实验研究表明，这种间歇性心肌再灌注形式可改善心肌灌注、维持内皮功能、减轻凋亡性细胞死亡、缩小心肌梗死面积、维持左心室收缩功能并降低死亡率。缺血后适应心脏保护作用的潜在机制是深入研究的主题。在本文中，我们综述了被认为是缺血后适应潜在介质的信号通路，对这些信号通路的识别提供了能够重现缺血后适应保护作用的新型心脏保护药理学靶点。
