McAllister Sandra E, Ashrafpour Homa, Cahoon Neil, Huang Ning, Moses Michael A, Neligan Peter C, Forrest Christopher R, Lipa Joan E, Pang Cho Y
Research Institute, The Hospital for Sick Children and Department of Surgery, University of Toronto, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
Am J Physiol Regul Integr Comp Physiol. 2008 Aug;295(2):R681-9. doi: 10.1152/ajpregu.90303.2008. Epub 2008 May 28.
We tested our hypothesis that postischemic conditioning (PostC) is effective in salvage of ischemic skeletal muscle from reperfusion injury and the mechanism involves inhibition of opening of the mitochondrial permeability transition pore (mPTP). In bilateral 8x13 cm pig latissimus dorsi muscle flaps subjected to 4 h ischemia, muscle infarction increased from 22+/-4 to 41+/-1% between 2 and 24 h reperfusion and remained unchanged at 48 (38+/-6%) and 72 (40+/-1%) h reperfusion (P<0.05; n=4 pigs). PostC induced by four cycles of 30-s reperfusion/reocclusion at the onset of reperfusion after 4 h ischemia reduced muscle infarction from 44+/-2 to 22+/-2% at 48 h reperfusion. This infarct protective effect of PostC was mimicked by intravenous injection of the mPTP opening inhibitor cyclosporin A or NIM-811 (10 mg/kg) at 5 min before the end of 4 h ischemia and was abolished by intravenous injection of the mPTP opener atractyloside (10 mg/kg) at 5 min before PostC (P<0.05; n=4-5 pigs). PostC or intravenous cyclosporin A injection at 5 min before reperfusion caused a decrease in muscle myeloperoxidase activity and mitochondrial free Ca2+ concentration and an increase in muscle ATP content after 4 h ischemia and 2 h reperfusion compared with the time-matched controls. These effects of PostC were abolished by intravenous injection of atractyloside at 5 min before PostC (P<0.05; n=6 pigs). These observations support our hypothesis that PostC is effective in salvage of ischemic skeletal muscle from reperfusion injury and the mechanism involves inhibition of opening of the mPTP.
缺血后适应（PostC）对挽救缺血骨骼肌免受再灌注损伤有效，其机制涉及抑制线粒体通透性转换孔（mPTP）的开放。在双侧8×13 cm猪背阔肌皮瓣经历4小时缺血后，在再灌注2至24小时期间，肌肉梗死面积从22±4%增加至41±1%，在再灌注48小时（38±6%）和72小时（40±1%）时保持不变（P<0.05；n = 4头猪）。在4小时缺血后再灌注开始时，通过四个30秒再灌注/再闭塞周期诱导的PostC将再灌注48小时时的肌肉梗死面积从44±2%降至22±2%。在4小时缺血结束前5分钟静脉注射mPTP开放抑制剂环孢素A或NIM-811（10 mg/kg）可模拟PostC的这种梗死保护作用，而在PostC前5分钟静脉注射mPTP开放剂苍术苷（10 mg/kg）则可消除这种作用（P<0.05；n = 4 - 5头猪）。与时间匹配的对照组相比，再灌注前5分钟进行PostC或静脉注射环孢素A可使4小时缺血和2小时再灌注后肌肉髓过氧化物酶活性和线粒体游离Ca2+浓度降低，肌肉ATP含量增加。在PostC前5分钟静脉注射苍术苷可消除PostC的这些作用（P<0.05；n = 6头猪）。这些观察结果支持了我们的假设，即PostC对挽救缺血骨骼肌免受再灌注损伤有效，其机制涉及抑制mPTP的开放。
