Klein H H, Pich S, Bohle R M, Lindert-Heimberg S, Nebendahl K
Division of Cardiology, Städt Krankenanstalten Idar-Oberstein GmbH, Germany, FRG.
Circulation. 2000 Oct 17;102(16):1977-82. doi: 10.1161/01.cir.102.16.1977.
This study investigated whether myocardial protection by inhibition of Na(+)/H(+) exchange (NHE) occurs during ischemia and/or during reperfusion.
The left anterior descending coronary artery was occluded in 32 pigs for 60 minutes and then reperfused for 24 hours. Infarct sizes (nitroblue tetrazolium [NBT] stain, histology) were determined at the end of the experiments. An extracorporeal bypass was used to achieve a constant residual blood flow of 3 mL/min in the myocardium at risk during ischemia. The NHE-1 inhibitor cariporide or distilled water was infused into the extracorporeal bypass system. In group 1, active treatment was administered from the onset of ischemia until 10 minutes of reperfusion (n=8). In group 2, active treatment was infused during the first 30 minutes of ischemia only (n=8). The group 3 animals (n=8) received intracoronary cariporide after 45 minutes of ischemia until 10 minutes of reperfusion. The control animals (group 4, n=7) were treated similarly to group 1 animals, with the cariporide solution being replaced by distilled water. Infarct sizes of group 1 (NBT stain, 41.5+/-20%; histology, 44. 6+/-12%) and group 2 (NBT stain, 33.5+/-14%; histology 34.9+/-15%) differed significantly (at least P:=0.012) from infarct sizes of group 3 (NBT stain, 71.6+/-15%; histology, 69.2+/-12%) and the control group (NBT stain, 76+/-9%; histology 72.4+/-12%). Cariporide treatment in group 1 and group 2 significantly improved functional recovery after 24 hours of reperfusion.
Myocardial protection by cariporide is predominantly achieved by NHE inhibition during ischemia and not during early reperfusion.
本研究调查了通过抑制钠氢交换（NHE）实现的心肌保护是否发生在缺血期间和/或再灌注期间。
32头猪的左冠状动脉前降支被阻断60分钟，然后再灌注24小时。在实验结束时测定梗死面积（硝基四氮唑蓝[NBT]染色、组织学）。在缺血期间，使用体外循环使处于危险中的心肌保持3 mL/min的恒定残余血流量。将NHE-1抑制剂卡立泊来德或蒸馏水注入体外循环系统。在第1组中，从缺血开始至再灌注10分钟给予积极治疗（n = 8）。在第2组中，仅在缺血的前30分钟内注入积极治疗药物（n = 8）。第3组动物（n = 8）在缺血45分钟后至再灌注10分钟接受冠状动脉内注射卡立泊来德。对照动物（第4组，n = 7）的治疗方式与第1组动物相似，用蒸馏水代替卡立泊来德溶液。第1组（NBT染色，41.5±20%；组织学，44.6±12%）和第2组（NBT染色，33.5±14%；组织学，34.9±15%）的梗死面积与第3组（NBT染色，71.6±15%；组织学，69.2±12%）和对照组（NBT染色，76±9%；组织学，72.4±12%）的梗死面积有显著差异（至少P = 0.012）。第1组和第2组的卡立泊来德治疗显著改善了再灌注24小时后的功能恢复。
卡立泊来德的心肌保护作用主要是通过在缺血期间而非早期再灌注期间抑制NHE来实现的。
