Vinten-Johansen Jakob
Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory Crawford Long Hospital, 550 Peachtree Street NE, Atlanta, GA 30308-2225, USA.
Heart Fail Rev. 2007 Dec;12(3-4):235-44. doi: 10.1007/s10741-007-9024-3.
Infarct size is determined not only by the duration and severity of ischemia, but also by pathological processes initiated at reperfusion (reperfusion injury). Numerous pharmacological strategies have been reported which administer drugs at or just before the onset of reperfusion, with subsequent salubrious effects, notably a reduction in infarct size. However, few if any of these strategies have become standard of care in the catheterization laboratory setting. Postconditioning, defined as repeated brief cycles of reperfusion interrupted by ischemia (or hypoxia) applied at the onset of reperfusion, was recently introduced as a mechanical strategy to attenuate reperfusion injury. Postconditioning intervenes only during the first few minutes of reperfusion. However, it reduces endothelial activation and dysfunction, the inflammatory response to reperfusion, necrosis, and apoptosis both acutely and long-term. Cardioprotection has been demonstrated by multiple independent laboratories and in multiple species. Postconditioning stimulates G-protein coupled receptors by their cognate endogenously released ligands and surprisingly activates survival kinases that may converge on mitochondrial K(ATP) channels and the permeability transition pore. Postconditioning has been shown in two clinical studies to reduce infarct size in patients undergoing percutaneous coronary intervention in the catheterization laboratory, and at least five other studies are in some phase of implementation. This significant reduction in infarct size has implications for reduction in heart failure as a consequence of myocardial infarction, but this link has yet to be demonstrated. The salubrious effects of postconditioning are an indirect validation of the experimental and clinical importance of reperfusion injury in the setting of coronary artery occlusion.
梗死面积不仅取决于缺血的持续时间和严重程度，还取决于再灌注时启动的病理过程（再灌注损伤）。已有众多药理学策略的报道，即在再灌注开始时或即将开始时给药，随后产生有益效果，尤其是梗死面积减小。然而，在导管实验室环境中，这些策略几乎没有成为标准治疗方法。后适应，定义为在再灌注开始时应用短暂的再灌注-缺血（或缺氧）反复循环，最近作为一种减轻再灌注损伤的机械策略被引入。后适应仅在再灌注的最初几分钟内起作用。然而，它能在急性和长期内减少内皮激活和功能障碍、对再灌注的炎症反应、坏死和凋亡。多个独立实验室已在多种物种中证实了其心脏保护作用。后适应通过其同源内源性释放的配体刺激G蛋白偶联受体，并且令人惊讶地激活可能汇聚于线粒体ATP敏感性钾通道和通透性转换孔的存活激酶。两项临床研究表明，后适应可减小导管实验室中接受经皮冠状动脉介入治疗患者的梗死面积，并且至少还有五项其他研究正处于实施的某个阶段。梗死面积的显著减小对减少心肌梗死导致的心力衰竭具有重要意义，但这种联系尚未得到证实。后适应的有益效果间接验证了冠状动脉闭塞情况下再灌注损伤在实验和临床方面的重要性。
