Cardioprotection at a distance: mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism

Abstract

Preconditioning in remote organs protects the myocardium; however, mediators of the protection remain unknown. Protection of the heart is linked to opioids; therefore, we hypothesized that mesenteric preconditioning (MPC) releases endogenous opioids that protect the myocardium from ischemic injury. In an intact rat model of myocardial infarction, all rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Prior to coronary artery occlusion, control rats were subjected to sham surgery in which the mesenteric artery was isolated but not occluded both with and without naloxone (10mg/kg) pretreatment. Experimental groups underwent isolation and occlusion of the mesenteric artery for 15 min followed by a 10 min reperfusion period with and without naloxone pretreatment. At the end of 2 h of coronary reperfusion, myocardial infarct size (IS) was determined by tetrazolium staining and expressed as a percent of the area at risk (AAR). Control rats had an IS/AAR of 57.3+/-2. MPC resulted in a significant reduction in infarct size compared to controls (32.2+/-3, P<0.001). Pretreatment with naloxone significantly attenuated the protective effects of MPC (53.8+/-4, P<0.0002). Therefore, it appears that MPC releases endogenous opioids that protect the myocardium from ischemic injury.