Mechanisms of Ca2+ overload in reperfused ischemic myocardium.
Mechanisms of Ca2+ overload in reperfused ischemic myocardium.
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DOI：
10.1146/annurev.ph.52.030190.002551
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发表时间：
1990
影响因子：
18.2
通讯作者：
Masato Tani
中科院分区：
文献类型：
--
作者：
Masato Tani
在严重损伤的心肌组织中，长时间缺血缺氧后的再灌流(3，26，61，73，83，)和复氧(14，27，28，57，58)均与CAH含量显著增加有关，而在非不可逆性损伤的心肌中未见CAH超载(36例)。CAH摄取增加与心肌机械功能恢复受抑相关(3，83)。因此，钙离子过度积聚被认为是不可逆转的心肌损伤和细胞坏死的主要事件[20]。在再灌流过程中，钙离子内流的增加超过了系统从胞浆中排出钙离子的处理能力，导致胞浆游离[Ca2+]升高。然而，导致再灌流时钙离子内流增加的确切机制尚未明确。肌膜离子转运系统的扰动似乎是缺氧心肌细胞中钙积累增加的原因，因为钙超载发生时，膜上没有明显的超微结构变化(14)。参与维持钙稳态的机制是复杂的，并与其他阳离子的调节系统相互关联。此外，膜完整性的丧失和通透性的增加可能是由内源性酶(即钙依赖的蛋白水解酶或脂肪酶)的作用引起的，这些酶由初始的
Both reperfusion (3, 26, 61, 73, 83, 89) and reoxygenation (14, 27, 28, 57, 58) after prolonged ischemia and hypoxia are associated with a large increase in CaH content in severely damaged myocardium, however CaH overload is not seen in the myocardium that is not irreversibly injured (36). Increased uptake of CaH correlates with the depressed recovery of mechanical function of the myocardium (3, 83). Therefore excessive Ca2+ accumulation has been implicated as a primary event in irreversible myocardial injury and cell necrosis (20). Increased influx of Ca2+ during reperfusion in excess of the handling capacity of systems for Ca2+ extrusion from the cytosol results in elevation of cytosolic-free [Ca2+]. Nevertheless, the exact mechanisms responsible for increased Ca2+ entry upon reperfusion have not been defined. Perturbations of ion transport systems in the sarcolemmal membrane appear to be responsible for increased Ca2+ accumulation in oxygen deficient myocytes because Ca2+ overload occurred without apparent ultrastructural changes in the membrane (14). The mechanisms involved in maintenance of Ca2+ homeostasis are complicated and interrelated with the regulatory systems of other cations. In addition, loss of membrane integrity and an increase in permeability can result from the action of endogenous enzymes (i.e. Ca2+ dependent proteases or lipases) that are activated secondarily by an initial