Mikhail Peter, Verma Subodh, Fedak Paul W M, Weisel Richard D, Li Ren-Ke
Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Canada.
Am J Cardiovasc Drugs. 2003;3(1):1-11. doi: 10.2165/00129784-200303010-00001.
This paper reviews significant work which has been done on ischemic preconditioning since its introduction by Murry et al. in 1986. This is a phenomenon where myocardial cells gain protection against long periods of ischemia by initially being exposed to brief episodes of ischemia followed by reperfusion. The molecular basis of ischemic preconditioning where adenosine, bradykinin and opioids are released, and eventually lead to the opening of mitochondrial ATP-sensitive potassium channels, is discussed in detail. There have been over 33 clinical studies to assess the clinical relevance of ischemic preconditioning. Many of these studies have looked at its benefit in patients undergoing percutaneous transluminal coronary angioplasty; others have looked at its use in open-heart surgery. There is no doubt that many of these studies support the clinical relevance of ischemic preconditioning, however, most of these studies have looked at surrogate markers, such as cardiac enzyme release, and left ventricular ejection fraction, but very few looked at the original endpoint, described by Murry et al., which is cell death. Larger trials, with morbidity and mortality being with the primary endpoints, are needed to confirm the clinical relevance of ischemic preconditioning.
本文回顾了自1986年默里等人提出缺血预处理以来所开展的重要研究工作。这是一种心肌细胞通过先经历短暂缺血发作再进行再灌注,从而获得针对长时间缺血的保护作用的现象。文中详细讨论了缺血预处理的分子基础,即腺苷、缓激肽和阿片类物质的释放,并最终导致线粒体ATP敏感性钾通道开放。已有超过33项临床研究评估缺血预处理的临床相关性。其中许多研究关注其在接受经皮腔内冠状动脉成形术患者中的益处;其他研究则关注其在心脏直视手术中的应用。毫无疑问,这些研究中有许多都支持缺血预处理的临床相关性,然而,这些研究大多关注替代指标,如心肌酶释放和左心室射血分数,而很少关注默里等人所描述的原始终点,即细胞死亡。需要开展以发病率和死亡率为主要终点的更大规模试验,以证实缺血预处理的临床相关性。