OBJECTIVES: This study sought to examine the effects of magnesium on epicardial action potential duration in patients during early myocardial ischemia. BACKGROUND: Magnesium has been shown to reduce arrhythmias in experimental models of myocardial ischemia. Experimental and clinical observations suggest an effect on repolarization. METHODS: Patients undergoing elective coronary artery bypass surgery were randomized (double blind) to receive intravenous magnesium (n = 10) or placebo (n = 10). Patients were placed on cardiopulmonary bypass and paced at 600 ms, and stable monophasic action potentials were obtained. Ischemia was achieved by aortic cross-clamping for 2 min while normothermia was maintained. RESULTS: Serum magnesium levels increased from 0.60 +/- 0.03 to 1.69 +/- 0.07 mmol/liter (mean +/- SEM) in the magnesium group, with no change in the placebo group. Epicardial temperature was identical in the two groups and did not alter during ischemia. At 90% repolarization, initial action potential prolongation was observed in the placebo group over the first minute of ischemia (282.0 +/- 6.0 to 294.0 +/- 4.8 ms) but not in the magnesium group (278.3 +/- 5.9 to 274.5 +/- 7.4 ms). At 2 min of ischemia, action potential duration was shorter in the magnesium group than in the placebo group (258.1 +/- 5.5 vs. 281.3 +/- 5.9 ms, respectively, p < 0.05). CONCLUSIONS: Intravenous magnesium infusion altered the epicardial action potential response to ischemia in patients. These findings may have important implications in the pathogenesis of arrhythmias in ischemic myocardium.