time Dependence of the Cardioprotective Effects of Lercanidipine

Lercanidipine is a new calcium antagonist derivative with slow onset and long-lasting action. In a previous work from our laboratory, lercanidipine was found to protect the myocardium against the deleterious effects of ischemia and reperfusion when administered before ischemia. To assess the timing of lercanidipine administration in relation to its ability to protect against ischemia and reperfusion damage, isolated rabbit hearts were perfused with different concentrations (10−7 and 10−8M) and durations of lercanidipine perfusion. After 30-min equilibration, hearts were perfused for 3 h at aerobic flow (22 ml/min), then subjected to global ischemia (at 1 ml/min) for 1 h, followed by 30-min reperfusion at 22 ml/min. Lercanidipine was infused at the two concentrations either at the onset of ischemia for 1 h or at the time of reperfusion for 30 min. Cardioprotection was evaluated in terms of mechanical function recovery on reperfusion. coronary effluent release of creatine phosphokinase, norepinephrine, lactate, and reduced and oxidized glutathione. Our data show that the cardioprotective action is achieved only if lercanidipine is administered at the onset of ischemia. Lercanidipine reduced the rise in diastolic pressure during ischemia and improved recovery on reperfusion only when given at 10−7M. At this concentration, lercanidipine reduced the release of creatine phosphokinase, an index of membrane disruption, and of norepinephrine, and diminished the oxidative stress accompanying reperfusion.