Delayed Postconditioning in the Mouse Heart In Vivo

Article

关键词: MITOCHONDRIAL PERMEABILITY TRANSITION;    ACUTE MYOCARDIAL-INFARCTION;    REPERFUSION INJURY;    INHIBITION;    APOPTOSIS;    ISCHEMIA;    PROTECTS;    PATHWAY;    MICE;    FORM;   

DOI  :  10.1161/CIRCULATIONAHA.111.031864

来源: SCIE

【 摘 要 】

Background-Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size. Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients. Methods and Results-Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR(60),). Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (Delta t) after reopening of the coronary artery (Delta t = 10 seconds, 1, 5, 10, 15, 20, 30, and 45 minutes; PostC(Delta t)). Infarct size/ area at risk was reduced by 71% in PostC(Delta 1) compared with IR(60), mice (P = 5 x 10(-6)). There was a linear correlation (r(2) = 0.91) between infarct size and Delta t, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when Delta t time increased. The protective effect of PostC(Delta 1) and PostC(Delta 15) was still effective when the duration of reperfusion was prolonged to 24 hours (IR(24 hours); PostC(Delta 1) and PostC(Delta 15) versus IR(24 hours), P = 0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release. Conclusions-This study in our in vivo mouse model of myocardial IR shows for the first time that delaying the intervention of postconditioning to 30 minutes does not abrogate the cardioprotective effect of postconditioning. This finding provides evidence that the time window of protection afforded by postconditioning may be larger than initially reported. (Circulation. 2011;124:1330-1336.)

【 授权许可】

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