title: Diastolic Ca2+ overload caused by Na+/Ca2+ exchanger during the first minutes of reperfusion results in continued myocardial stunning.
abstract: 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 Ca(2+) overload without significant changes in systolic Ca(2+) and the amplitude of Ca(2+) transient during the first 10 min of reperfusion played an important role in the occurrence of myocardial stunning. Decreasing Ca(2+) entry into myocardial cells with low Ca(2+) reperfusion was a very efficient way to prevent myocardial stunning. Diastolic Ca(2+) overload was closely related to the reverse mode of Na(+)/Ca(2+) exchanger (NCX) rather than L-type Ca(2+) 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 Ca(2+) 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 Ca(2+) overload caused by activation of the reverse mode of NCX of cardiomyocytes during the initial period of reperfusion following brief ischemia.
authors.affiliation: Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Geng-Ze
authors.initials: GZ
authors.lastname: Wei
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Bi
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Ding-Hua
authors.initials: DH
authors.lastname: Yi
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Yu
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Pei
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D003971:Diastole; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology