期刊
BASIC RESEARCH IN CARDIOLOGY
卷 103, 期 5, 页码 472-484出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-008-0731-2
关键词
infarct size; K-ATP channels; mitochondrial permeability transition pore; postconditioning; reperfusion injury
资金
- National Institute of Health [HL64886]
- Carlyle Fraser Foundation of Emory Crawford Long Hospital
- [HL69487]
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 K-ATP 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 K-ATP channel blocker was infused 5 min before Postcon; HMR1098: the sarcolemmal K-ATP channel blocker was administered 5 min before Postcon. After 24 h of R, infarct size was smaller in Postcon relative to Control (27 +/- 4%* Vs. 39 +/- 2% of area at risk), consistent with a reduction in CK activity (66 +/- 7* Vs. 105 +/- 7 IU/g). The infarct-sparing effect of Postcon was blocked by 5-HD (48 +/- 5%(dagger)), but was not altered by HMR1098 (29 +/- 3%*), consistent with the change in CK activity (102 +/- 8(dagger) in 5-HD and 71 +/- 6* IU/g in HMR1098). In H9c2 cells exposed to 8 h hypoxia and 3 h of reoxygenation, Postcon up-regulated expression of mito-K-ATP channel Kir6.1 protein, maintained mitochondrial membrane potential and inhibited mitochondrial permeability transition pore (mPTP) opening evidenced by preserved fluorescent MIZE 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 K-ATP channels and inhibiting mPTP opening. *P < 0.05 Vs. Control; P-dagger < 0.05 Vs. Postcon.
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