Beneficial Effects of Diltiazem on the Ischemic Derangements of the Myocardial Metabolism Assessed by 31P-NMR in the Isolated Perfused Rat Heart

Abstract

Using the isolated perfused heart preparations of the rat, effects of diltiazem, a calcium antagonist, on the ischemic derangements of the mechanical function and the energy metabolism of the ventricular myocardium were studied. The myocardial tissue levels of creatine phosphate (CP), ATP, inorganic phosphate (Pi) and pH were determined with 31P-NMR. Global ischemia was induced by cross-clamping of the aortic inflow line for 15 min, which resulted in a fall of CP, ATP and pH and a rise of Pi. The test hearts were perfused with diltiazem-containing solution (10-7, 10-6 and 10-5 M) for 12 min prior to the induction of the global ischemia. A significant dose-related decline of the myocardial mechanical function expressed as (left ventricular pressure) .times. (heart rate) was observed in diltiazem-treated hearts. In doses above 10-6 M, diltiazem delayed the onset of the fall of the myocardial CP and pH levels and the rise of Pi induced by ischemia, and there was an excellent correlation between the suppression of the myocardial mechanical function observed before induction of ischemia and the level of the myocardial CP and pH at the initial phase of ischemia, indicating that the improvement of the myocardial energy metabolism was due to the cardiodepressant effects of the compound.