Tang Xian-Liang, Sato Hiroshi, Tiwari Sumit, Dawn Buddhadeb, Bi Qiuli, Li Qianhong, Shirk Gregg, Bolli Roberto
Division of Cardiology, Univ. of Louisville, Louisville, KY 40202, USA.
Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2308-17. doi: 10.1152/ajpheart.00479.2006. Epub 2006 Jun 30.
Brief episodes of ischemia and reperfusion after a lethal ischemic insult confer cardioprotection, a phenomenon termed "ischemic postconditioning." However, all studies reported to date have been conducted in open-chest animal models. We sought to determine whether postconditioning occurs in conscious animals and whether it protects against severe myocardial injury.
Chronically instrumented rats were assigned to a 30- (Subset 1), 45- (Subset 2), or 60-min (Subset 3) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control), were preconditioned with 12 cycles of 2-min occlusion/2-min reperfusion immediately (early preconditioning; EPC) or 24 h (late preconditioning; LPC) before myocardial infarction, or were postconditioned with 20 cycles of 10-s occlusion/10-s reperfusion immediately after myocardial infarction (20-10 PostC).
With a 30-min occlusion, infarct size (54.4 +/- 2.3% of risk region in control-30) was significantly reduced in EPC-30, LPC-30, and 20-10 PostC-30 groups (by 72, 70, and 47%, respectively; all P < 0.05 vs. control-30). With a 45-min occlusion, infarct size (62.2 +/- 2.4% in control-45) was reduced in EPC-45 and LPC-45 groups (by 47 and 41%, respectively; all P < 0.05 vs. control-45) but not in the 20-10 PostC-45 group [55.4 +/- 2.3%, P = not significant (NS) vs. control-45]. With a 60-min occlusion, infarct size (72.7 +/- 2.2% in control-60) was reduced in the EPC-60 (by 20%, P < 0.05) but not in the LPC-60 (63.6 +/- 2.5%, P = NS) or in the 20-20 PostC group (71.5 +/- 3.4%, P = NS).
Both early and late ischemic preconditioning as well as ischemic postconditioning confer protection in conscious rats; however, unlike early preconditioning, postconditioning protects only against coronary occlusions <45 min. In the conscious rat, the cardioprotection afforded by postconditioning is limited to mild to moderate myocardial injury.
致死性缺血损伤后的短暂缺血和再灌注发作可赋予心脏保护作用,这一现象被称为“缺血后适应”。然而,迄今为止报道的所有研究均在开胸动物模型中进行。我们试图确定后适应是否发生在清醒动物中,以及它是否能预防严重心肌损伤。
将长期植入仪器的大鼠分为三组,分别进行30分钟(子集1)、45分钟(子集2)或60分钟(子集3)的冠状动脉闭塞,随后再灌注24小时。在每个子集中,大鼠不接受进一步干预(对照组),在心肌梗死前立即接受12个循环的2分钟闭塞/2分钟再灌注预处理(早期预处理;EPC)或24小时(晚期预处理;LPC),或在心肌梗死后立即接受20个循环的10秒闭塞/10秒再灌注后处理(20-10后适应)。
在30分钟闭塞时,EPC-30、LPC-30和20-10后适应-30组的梗死面积(对照组-30中为危险区域的54.4±2.3%)显著减小(分别减少72%、70%和47%;与对照组-30相比,所有P<0.05)。在45分钟闭塞时,EPC-45和LPC-45组的梗死面积(对照组-45中为62.2±2.4%)减小(分别减少47%和41%;与对照组-45相比,所有P<0.05),但20-10后适应-45组未减小[55.4±2.3%,与对照组-45相比,P=无显著差异(NS)]。在60分钟闭塞时,EPC-60组的梗死面积(对照组-60中为72.7±2.2%)减小(减少20%,P<0.05),但LPC-60组未减小(63.6±2.5%,P=NS),20-20后适应组也未减小(71.5±3.4%,P=NS)。
早期和晚期缺血预处理以及缺血后适应均可在清醒大鼠中提供保护作用;然而,与早期预处理不同,后适应仅对<45分钟的冠状动脉闭塞具有保护作用。在清醒大鼠中,后适应提供的心脏保护作用仅限于轻度至中度心肌损伤。