Adenosine and cardioprotection during reperfusion - an overview
Adenosine and cardioprotection during reperfusion - an overview
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DOI：
10.1023/a:1025454504577
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发表时间：
2003-09-01
影响因子：
4.3
通讯作者：
Gelpi, RJ
中科院分区：
文献类型：
--
作者：
Donato, M;Gelpi, RJ
缺血性心脏病包括许多实体已根据病理生理学和演变标准分组。近年来，人们描述了“新的”缺血综合征。在“新的”缺血综合征中，心室缺血后功能障碍-也称为“顿抑心肌”-值得一提。在这一途径中，一些研究表明再灌注本身可能导致细胞损伤（再灌注损伤）。在过去的几年中，对心脏缺血和再灌注引起的损伤的保护作用已归因于腺苷。这些效应已在不同的体内和体外实验模型中得到证实。因此，在缺血前给予外源性腺苷或腺苷受体激动剂可减小梗塞的大小，改善再灌注期间心室功能的恢复（减弱顿抑），并缩短缺血性挛缩的时间。然而，着眼于潜在的治疗应用，它是最重要的是找到这种保护，并了解所涉及的机制时，程序应用于早期reperfusion.We表明，腺苷，从一开始的再灌注，衰减收缩和舒张（心肌硬度）的顿抑心肌的改变。这种保护作用是通过激活A（1）腺苷受体介导的，而对梗死面积没有影响。根据一些作者的说法，腺苷可以减少再灌注早期内皮素的释放，并减少可能导致细胞损伤的Ca 2+过载。最后，缺血预处理涉及一系列细胞内事件，这些事件起始于A（1）受体的激活，并终止于线粒体的敏感的K+ ATP通道。这些通道的磷酸化和开放将导致保护作用。在再灌注过程中这种特殊机制的激活尚未得到广泛研究。
Ischemic heart disease includes a number of entities that have been grouped in accordance with physiopathology and evolutive criteria. In recent years 'new' ischemic syndromes have been described. Within the 'new' ischemic syndromes, ventricular post-ischemic dysfunction - also known as 'stunned myocardium' - is worth mentioning. In this route, several studies have suggested that reperfusion per se could cause cellular injury ( reperfusion injury). In previous years, a protective effect on the injury caused by ischemia and reperfusion in the heart has been attributed to adenosine. These effects have been documented in different experimental in vivo and in vitro models. Thus, the administration of exogenous adenosine, or agonists of adenosine receptors prior to ischemia reduces the size of the infarction, improves the recovery of the ventricular function during reperfusion ( attenuating stunning) and prolongs the time period to the ischemic contracture. However, focusing on a potential therapeutic application, it is of the utmost importance to find this protection and learn the mechanisms involved when procedures are applied during early reperfusion.We showed that adenosine, administered from the beginning of reperfusion, attenuated systolic and diastolic ( myocardial stiffness) alterations of the stunned myocardium. This protective effect was mediated by the activation of A(1) adenosine receptors, and without modification on infarct size. According to some authors, adenosine can decrease the release of endothelin, during early reperfusion, and reduce an overload of Ca2+ that could cause a cellular lesion. Finally, ischemic preconditioning involves a series of intracellular events that are initiated with the activation of the A(1) receptor, and end at the sensitive K+ ATP channels of the mitochondria. The phosphorylation and opening of these channels would cause the protective effect. Activation of this specific mechanism during reperfusion has not been studied extensively.