Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 572, Issue 1, Pages 1-11Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2007.05.065
Keywords
diastolic Ca2+ overload; Na+/Ca2+ exchanger; myocardial stunning
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The pathogenesis of myocardial stunning caused by brief ischemia and reperfusion remains unclear. The aim of the present study was to investigate the underlying mechanism of myocardial stunning, An isolated cell model of myocardial stunning was firstly established in isolated rat ventricular myocytes exposed to 8 min of simulated ischemia and 30 min of reperfusion, the cardiomyocyte contractile function was used to evaluate myocardial stunning. A diastolic Ca2+ overload without significant changes in systolic Ca2+ and the amplitude of Ca2+ transient during the first 10 min of reperfusion played an important role in the occurrence of myocardial stunning. Decreasing Ca2+ entry into myocardial cells with low Ca2+ reperfitsion was a very efficient way to prevent myocardial stunning. Diastolic Ca2+ overload was closely related to the reverse mode of Na+/Ca2+ exchanger (NCX) rather than L-type Ca2+ channel. The activity of the reverse mode of NCX was found significantly higher at the initial time of reperfusion, and KB-R7943, a selective inhibitor of the reverse mode of NCX, administered at first 10 min of reperfusion rather than at the time of ischemia significantly attenuated myocardial stunning. In addition, NCX inhibition also attenuated the Ca2+ oscillation and cardiac dysfunction when field stimulus was stopped at first 10 min of reperfusion. These data suggest that one of the important mechanisms of triggering myocardial stunning is diastolic Ca2+ overload caused by activation of the reverse mode of NCX of cardiomyocytes during the initial period of reperfusion following brief ischemia. (C) 2007 Published by Elsevier B.V.
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