Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion

Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion
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DOI:
10.1016/j.cardiores.2004.01.006
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发表时间:
2004-04-01
影响因子:
10.8
通讯作者:
Vinten-Johansen, J
Vinten-Johansen, J
中科院分区:
医学1区
文献类型:
--
作者:
Kin, H;Zhao, ZQ;Vinten-Johansen, J

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目的:我们先前表明,短暂的间歇性缺血应用于再灌注开始期间(即,后处理)在犬缺血-再灌注模型中具有心脏保护作用。本研究验证了这一假设,即再灌注(R)的早期分钟,在此期间应用后处理(Post-con)是其心脏保护的关键。方法:麻醉开胸大鼠,结扎左冠状动脉(LCA)30 min,再灌注3 h。所有大鼠随机分为6组:对照组(n = 8):R时不干预;缺血预处理组(n = 8):在首次阻断前阻断LCA 5 min,然后再阻断10 min;术后2(n = 8):在R的前2分钟内应用6个周期的10 s R和10 s再闭塞;延迟术后(n = 8):在R的第1分钟内松开结扎线以实现完全复流,之后应用3个周期的术后算法;假手术(n = 6):手术过程与其他组相同,但不结扎LCA结扎线。结果如下:通过血浆肌酸激酶活性(18 +/- 2* vs. 46 +/- 6 IU/g蛋白)证实,Postcon 1(40 +/- 2%*)中的细胞大小(TTC染色)比对照组(52 +/- 3%)小23%。6个周期的后处理没有进一步减少梗死面积(40 +/-2.9%,p>0.05 vs.后处理1)。同时,IPC组的梗死面积缩小(17 ± 3%)显著大于Post-con 1组(p
Objective: We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection. Methods: In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n = 8): no intervention at R; Ischemic preconditioning (IPC) (n = 8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n = 8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n = 8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n = 8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n = 6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated. Results: Infarct size (TTC staining) was 23% smaller in Postcon 1 (40 +/- 2%*) than in Control (52 +/- 3%), confirmed by plasma creatine kinase activity (18 +/- 2* vs. 46 +/- 6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40 +/- 2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17 +/- 3%) than in Post-con 1 (p