心肌缺血后处理的研究进展

Advances in Research of Postconditioning of Heart

缺血后处理是指心肌发生缺血后,在长时间的再灌注之前进行数次短暂再灌注/缺血的循环,是近年提出的一种新的减轻再灌注损伤的方法,赵志清等首先在犬的在体缺血再灌模型中,发现缺血后处理可以缩小心肌梗死范围,具有心肌保护作用,Galagudza等在鼠的离体缺血再灌模型中证实缺血后处理可降低缺血/再灌注损伤引起的心室颤动,有抗心律失常作用,Staat等在临床上证实了缺血后处理的心肌保护作用。缺血后处理的保护机制可能与氧自由基的生成减少、内源性活性物质的释放、膜通道功能状态的变化和蛋白激酶的活化有关,现就缺血后处理的发现、机理和临床应用作一简要综述。

Postconditioning is a series of brief mechanical interruptions of reperfusion following a specific prescribed algorithm applied at the very onset of reperfusion. Postconditioning is a strategy that can modify reperfusion-induced adverse events. Zhao et al. first reported that postconditioning reduced infarct size in vivo dog model. Galagudza et al. manifest that postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias in the isolated rat heart model. The study by Staat et al. compellingly supports the notion that reperfusion damage is a clinical entity rather than a laboratory curiosity. The cardioprotection was associated with a reduction in oxygen free radical and tissue superoxide anion generation. Postconditioning sets in motion triggers and signals that are functionally related to reduced cell death. Adenosine has been implicated in the cardioprotection of postconditioning, as has e-NOS,endothelial nitric oxide synthase. Postconditioning can change the function of channels. Opening of KATP channels and closing of the mitochondrial permeability transition pore play an important role in the cardioprotection by postconditioning. Cardioprotection by postconditioning has also been associated with the activation of intracellular survival pathways such as ERK1/2 and PI3 kinase-Akt pathways. This review discusses the discovery, development, mechanisms and clinical application of posteonditioning.