Naloxone Blockade of Myocardial Ischemic Preconditioning is Stereoselective

This study tested the hypothesis that endogenous opioids are involved in the infarct limitation of myocardial ischemic preconditioning (IP). Blockade of IP-induced infarct limitation by (−)naloxone hydrochloride (−NAL) or its receptor-inactive stereoisomer (+)naloxone (+NAL) was evaluated. Fifty-two pentobarbitone-anesthetized, open-chest rabbits underwent 30 min coronary artery occlusion and 180 min reperfusion. Treatment groups were: control (n=9), IP (n=8), −NAL (n=9) and −NAL/IP (n=12), or +NAL (n=6) and +NAL/IP (n=8). IP was elicited with 5 min regional ischemia, beginning 15 min before the 30 min coronary occlusion. −NAL or +NAL, 3 mg/kg i.v. bolus, was given 25 min before the 30 min coronary occlusion. Infarct size was assessed with tetrazolium and expressed as a percentage of area-at-risk. There were no significant intergroup differences of area-at-risk. IP resulted in marked infarct limitation compared to control (control, 32.9±7.6%vIP, 5.8±4.5%;P=0.04). Neither −NAL nor +NAL alone altered infarct size compared to control, but −NAL did block the infarct limitation of IP (−NAL, 31.4±6.7%v−NAL/IP, 24.3±6.2%) whereas +NAL did not (+NAL, 40.5±5.0%v+NAL/IP, 13.7±3.6%;P=0.02). In conclusion, naloxone blockade of IP-induced cardioprotection is stereospecific and therefore likely to be opioid receptor-mediated.