Both D-cis- and L-cis-diltiazem attenuate hydrogen peroxide-induced derangements in rat hearts

The effects of D-cis- and L-cis-diltiazem on the hydrogen peroxide (H2O2)-induced derangements of mechanical function and energy metabolism, and accumulation of intracellular Na+ were studied in isolated rat hearts. The intracellular concentration of Na+ ([Na+]i) in the myocardium was measured using a nuclear magnetic resonance technique. H2O2 (600 microM) increased the left ventricular end-diastolic pressure, decreased the tissue level of ATP, and increased the release of lactate dehydrogenase from the myocardium. These alterations induced by H2O2 were significantly attenuated by D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). H2O2 (1 mM) produced a marked increase in the myocardial [Na+]i, which was effectively inhibited by tetrodotoxin (3 microM), D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). These results suggest that both D-cis- and L-cis-diltiazem protect the myocardium against the H2O2-induced derangements in the isolated, perfused rat heart. The protective action of D-cis- and L-cis-diltiazem may be due to their ability to inhibit the H2O2-induced increase in [Na+]i, at least in part.