Garcia-Dorado David, Agulló Luis, Sartorio Carmem Lluisa, Ruiz-Meana Marisol
Laboratorio de Cardiología Experimental, Area del Cor, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Thromb Haemost. 2009 Apr;101(4):635-42.
Reperfusion injury may cause myocardial cell death and limit the benefit achieved by restoration of coronary artery patency in patients with acute myocardial infarction. The mechanism includes altered Ca(2+) handling with cytosolic and mitochondrial Ca(2+) overload, Ca(2+)- and ATP-dependent hypercontraction, cytoskeletal fragility, mitochondrial permeability transition and gap junction-mediated propagation of cell death, as well as alterations in non-cardiomyocyte cells, in particular platelets and endothelial cells. cGMP modulates favorably all these mechanism, mainly through PKG-mediated actions, but cGMP synthesis is altered in reperfused cardiomyocytes and endothelial cells by mechanisms that are only partially understood. Stimulation of cGMP synthesis during initial reperfusion by means of natriuretic peptides has been found protective in different animal models and in patients. Moreover, increasing evidence indicates that cGMP is an important step in signal transduction of endogenous cardioprotection. Thus, the cGMP pathway appears as a key element in the pathophysiology of myocardial ischaemia-reperfusion and as a promising therapeutic target in patients with acute myocardial infarction.
再灌注损伤可能导致心肌细胞死亡，并限制急性心肌梗死患者冠状动脉再通所带来的益处。其机制包括钙（Ca2+）处理异常，伴有胞质和线粒体钙超载、钙和ATP依赖的过度收缩、细胞骨架脆弱、线粒体通透性转换以及间隙连接介导的细胞死亡传播，以及非心肌细胞，特别是血小板和内皮细胞的改变。环磷酸鸟苷（cGMP）主要通过蛋白激酶G（PKG）介导的作用对所有这些机制产生有利调节，但再灌注心肌细胞和内皮细胞中的cGMP合成通过仅部分了解的机制发生改变。在不同动物模型和患者中，已发现利用利钠肽在初始再灌注期间刺激cGMP合成具有保护作用。此外，越来越多的证据表明，cGMP是内源性心脏保护信号转导中的重要一步。因此，cGMP途径似乎是心肌缺血-再灌注病理生理学中的关键因素，也是急性心肌梗死患者有前景的治疗靶点。
