Energy preserving effect of l-cis diltiazem in isolated ischemic and reperfused guinea pig hearts: a P-31-NMR study

We determined the effect of l-cis diltiazem, the enantiomer of diltiazem (d -cis isoform), on the energy metabolism of isolated guinea pig hearts durin g ischemia-reperfusion. We used P-31-NMR to measure the high-energy phospha te content and intracellular pH (pH(i)) during global ischemia for 30 min f ollowed by reperfusion for 30 min. Before ischemia, the left ventricular de veloped pressure (LVDP) was reduced less by 10 mu M l-cis diltiazem than by 3 mu M diltiazem or 500 nM nifedipine. However, 10 mu M l-cis diltiazem pr eserved the intracellular ATP content during ischemia and reperfusion, redu ced the end-diastolic pressure increase during ischemia and reperfusion, an d restored LVDP after reperfusion. Nifedipine at 50 nM, which reduced the L VDP more than 10 mu M l-cis diltiazem, showed no cardioprotective effect. T en micromolar l-cis diltiazem and 3 mu M diltiazem, but neither 50 nor 500 nM nifedipine, reduced the pH(i) decrease that occurred 25 or 30 min after the onset of ischemia. Therefore, l-cis diltiazem has a cardioprotective ef fect on ischemic and reperfused myocardium and is less cardiodepressive tha n diltiazem and nifedipine. The effect of l-cis diltiazem during ischemia a nd reperfusion involves energy preservation, which is probably independent of its Ca2+-channel blocking action.