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 (IF). Blockade of IF-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). LP 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% v IP, 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 optoid receptor-mediated. (C) 1996 Academic Press Limited