Using an isolated perfused rat heart preparation, the protective effects of lidocaine and diltiazem on ischemic derangements of myocardial energy metabolism were studied with 31P-nuclear magnetic resonance spectroscopy. The hearts were perfused with a solution containing lidocaine (4.27 x 10(-5), 12.80 x 10(-5) M) or diltiazem (2.22 x 10(-7), 2.22 x 10(-6) M) for 15 min prior to the induction of global ischemia. The decrease in myocardial oxygen consumption rate, assessed as the product of heart rate and left ventricular systolic pressure (HR x LVP), was greater in diltiazem-treated than in lidocaine-treated hearts. Diltiazem and lidocaine significantly retarded the fall in myocardial pH during ischemia and improved ATP recovery after reperfusion. There was a good correlation between suppression of HR x LVP observed before induction of ischemia and decreased drop in pH during the early phase of ischemia in the diltiazem-treated groups (r = -0.78, p less than 0.01), but not in the lidocaine-treated groups. These results indicate that the beneficial effects of diltiazem on the ischemic myocardium are due primarily to the cardio-depressant effects. The beneficial effects of lidocaine cannot, however, be explained solely on the basis of the depression of oxygen consumption.