Effects of naloxone on myocardial ischemic preconditioning in humans

OBJECTIVES We attempted to establish whether naloxone, an opioid receptor antagonist, abolishes the adaptation to ischemi observed in humans during coronary angioplasty after repeated balloon inflations. BACKGROUND Experimental studies indicate that myocardial opioid receptors are involved in ischemic preconditioning. METHODS Twenty patients undergoing angioplasty for an isolated stenosis of major epicardial coronary artery were randomized to receive intravenous infusion of naloxone or placebo during the procedure. Intracoronary electrocardiogram and cardiac pain (using 100-mm visual analog scale) were determined at the end of the first two balloon inflations. Average peak velocity in the contralateral coronary artery during balloon occlusion, an index of collateral recruitment, was also assessed by using Doppler guide wire in the six patients of each group with stenosis on the left anterior descending coronary artery. RESULTS In naloxone-treated patients, ST-segment changes and cardiac pain severity during the second inflation were similar to those observed during the first inflation (12 ± 6 vs. 11 ± 7 mm, p = 0.3, and 58 ± 13 vs. 56 ± 12 mm, p = 0.3, respectively), whereas in placebo-treated patients, they were significantly less (6 ± 3 vs. 13 ± 6 mm, p = 0.002 and 31 ± 21 vs. 55 ± 22 mm, p = 0.008, respectively). In both naloxone- and placebo-treated patients, average peak velocity significantly increased from baseline to the end of the first inflation (p = 0.04 and p = 0.02, respectively), but it did not show any further increase during the second inflation. CONCLUSIONS The adaptation to ischemi observed in humans after two sequential coronary balloon inflations is abolished by naloxone and is independent of collateral recruitment. Thus, it is due to ischemic preconditioning and is, at least partially, mediated by opioid receptors, suggesting their presence in the human heart.