期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 289, 期 2, 页码 H614-H623出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00101.2005
关键词
isolated cardiomyocytes; oxidative stress; ischemic preconditioning
Extracellular ATP is known to augment cardiac contractility by increasing intracellular Ca2+ concentration ([Ca2+](i)) in cardiomyocytes; however, the status of ATP-mediated Ca2+ mobilization in hearts undergoing ischemia-reperfusion (I/R) has not been examined previously. In this study, therefore, isolated rat hearts were subjected to 10 - 30 min of global ischemia and 30 min of reperfusion, and the effect of extracellular ATP on [Ca2+](i) was measured in purified cardiomyocytes by fura-2 microfluorometry. Reperfusion for 30 min of 20-min ischemic hearts, unlike 10-min ischemic hearts, revealed a partial depression in cardiac function and ATP-induced increase in [Ca2+](i); no changes in basal [Ca2+](i) were evident in 10- or 20-min I/R preparations. On the other hand, reperfusion of 30-min ischemic hearts for 5, 15, or 30 min showed a marked depression in both cardiac function and ATP-induced increase in [Ca2+](i) and a dramatic increase in basal [Ca2+](i). The positive inotropic effect of extracellular ATP was attenuated, and the maximal binding characteristics of S-35-labeled adenosine 5'-[gamma-thio] triphosphate with crude membranes from hearts undergoing I/R was decreased. ATP-induced increase in [Ca2+](i) in cardiomyocytes was depressed by verapamil and Cibacron Blue in both control and I/R hearts; however, this response in I/R hearts, unlike control hearts, was not affected by ryanodine. I/R-induced alterations in cardiac function and ATP-induced increase in [Ca2+](i) were attenuated by treatment with an antioxidant mixture and by ischemic preconditioning. The observed changes due to I/R were simulated in hearts perfused with H2O2. The results suggest an impairment of extracellular ATP-induced Ca2+ mobilization in I/R hearts, and this defect appears to be mediated through oxidative stress.
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