Gho B C, Schoemaker R G, van den Doel M A, Duncker D J, Verdouw P D
Thoraxcenter, Erasmus University Rotterdam, Netherlands.
Circulation. 1996 Nov 1;94(9):2193-200. doi: 10.1161/01.cir.94.9.2193.
Brief coronary artery occlusions (CAOs) protect both the artery's own perfusion territory ("myocardial preconditioning") and adjacent "virgin" myocardium. Whether ischemia in remote organs protects myocardium is unknown. We examined whether brief occlusion of the anterior mesenteric artery (MAO) or left renal artery (RAO) protects against myocardial infarction.
Area at risk (AR) and infarcted area (IA) were determined in anesthetized rats after 180 minutes of reperfusion following a 60-minute CAO. At normothermia (body temperature, 36.5 degrees C to 37.5 degrees C), IA/AR was 68 +/- 2% (mean +/- SEM, n = 11) in control rats and 50 +/- 3% (n = 9, P < .001) in rats preconditioned by 15-minute CAO 10 minutes before 60-minute CAO. A 15-minute MAO was equally protective (IA/AR = 50 +/- 3%, n = 10, P < .001), whereas 15-minute RAO failed to limit IA/AR (72 +/- 5%, n = 8). Hypothermia (body temperature, 30 degrees C to 31 degrees C) did not affect IA/AR (67 +/- 3%, n = 11) in control animals but enhanced protection by 15-minute CAO (IA/AR = 22 +/- 3%, n = 8), whereas protection by 15-minute MAO (IA/AR = 44 +/- 5%, n = 11, P < .001) was minimally enhanced. Hypothermia unmasked protection by 15-minute RAO (IA/AR = 46 +/- 6%, n = 9, P < .01). Hexamethonium (20 mg/kg IV) did not alter protection by 15-minute CAO, but it abolished protection by 15-minute MAO. When MAO was sustained throughout the study, cardioprotection was absent.
Brief ischemia in "remote" organs protects myocardium against infarction as effectively as myocardial preconditioning. The mechanism of protection by MAO differs from that of CAO, because ganglion blockade abolished protection by MAO but not by CAO. The neurogenic pathway is activated during reperfusion after 15-minute MAO, because sustained MAO failed to produce cardioprotection.
短暂冠状动脉闭塞（CAO）可保护动脉自身的灌注区域（“心肌预处理”）以及相邻的“未受损”心肌。远处器官的缺血是否能保护心肌尚不清楚。我们研究了短暂阻断肠系膜前动脉（MAO）或左肾动脉（RAO）是否能预防心肌梗死。
在60分钟CAO后再灌注180分钟的麻醉大鼠中测定危险区域（AR）和梗死面积（IA）。在正常体温（体温36.5℃至37.5℃）下，对照组大鼠的IA/AR为68±2%（平均值±标准误，n = 11），在60分钟CAO前10分钟经15分钟CAO预处理的大鼠中为50±3%（n = 9，P <.001）。15分钟的MAO具有同样的保护作用（IA/AR = 50±3%，n = 10，P <.001），而15分钟的RAO未能限制IA/AR（72±5%，n = 8）。低温（体温30℃至31℃）对对照组动物的IA/AR无影响（67±3%，n = 11），但增强了15分钟CAO的保护作用（IA/AR = 22±3%，n = 8），而15分钟MAO的保护作用（IA/AR = 44±5%，n = 11，P <.001）仅略有增强。低温使15分钟RAO的保护作用显现出来（IA/AR = 46±6%，n = 9，P <.01）。六甲铵（20 mg/kg静脉注射）未改变15分钟CAO的保护作用，但消除了15分钟MAO的保护作用。当在整个研究过程中持续MAO时，心脏保护作用消失。
“远处”器官的短暂缺血对心肌梗死的保护作用与心肌预处理一样有效。MAO的保护机制与CAO不同，因为神经节阻断消除了MAO的保护作用，但未消除CAO的保护作用。在15分钟MAO后的再灌注过程中神经源性途径被激活，因为持续的MAO未能产生心脏保护作用。
