Myocardial Protection by Brief Ischemia in Noncardiac Tissue

Abstract

Background 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. Methods and Results 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°C to 37.5°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°C to 31°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. Conclusions 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.