Persistent beneficial effect of postconditioning against infarct size: Role of mitochondrial KATP channels during reperfusion

James Mykytenko, James Reeves, Hajime Kin, Ningping Wang, Amanda Zatta, Rong Jiang, Robert Guyton, Jakob Vinten-Johansen, Zhi-Qing Zhao

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71 Citations (Scopus)

Abstract

Abstract This study tested the hypothesis that inhibition of myocardial injury and modulation of mitochondrial dysfunction by postconditioning (Postcon) after 24 h of reperfusion is associated with activation of KATP channels. Thirty dogs undergoing 60 min of ischemia and 24 h of reperfusion (R) were randomly divided into four groups: Control: no intervention at R; Postcon: three cycles of 30 s R alternating with 30 s reocclusion were applied at R; 5-hydroxydecanoate (5-HD): the mitochondrial KATP channel blocker was infused 5 min before Postcon; HMR1098: the sarcolemmal KATP channel blocker was administered 5 min before Postcon. After 24 h of R, infarct size was smaller in Postcon relative to Control (27 A? 4 * Vs. 39 A? 2 of area at risk), consistent with a reduction in CK activity (66 A? 7* Vs. 105 A? 7 IU/g). The infarct-sparing effect of Postcon was blocked by 5-HD (48 A? 5 ), but was not altered by HMR1098 (29 A? 3 *), consistent with the change in CK activity (102 A? 8 in 5-HD and 71 A? 6* IU/g in HMR1098). In H9c2 cells exposed to 8 h hypoxia and 3 h of reoxygenation, Postcon up-regulated expression of mito-KATP channel Kir6.1 protein, maintained mitochondrial membrane potential and inhibited mitochondrial permeability transition pore (mPTP) opening evidenced by preserved fluorescent TMRE and calcein staining. The protective effects were blocked by 5-HD, but not by HMR1098. These data suggest that in a clinically relevant model of ischemia-reperfusion (1) Postcon reduces infarct size and decreases CK activity after prolonged reperfusion; (2) protection by Postcon is achieved by opening mitochondrial KATP channels and inhibiting mPTP opening. *P <0.05 Vs. Control; P <0.05 Vs. Postcon.
Original languageEnglish
Pages (from-to)472 - 484
Number of pages13
JournalBasic Research in Cardiology
Volume103
Issue number5
Publication statusPublished - 2008

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