Effects of nicardipine on myocardial function in vitro and in vivo

Nicardipine is a second-generation dihydropyridine calcium antagonist with relative coronary and cerebrovascular selectivity. To study the effects of nicardipine on systolic and diastolic myocardial function, we used three experimental models. In isolated feline papillary muscle, nicardipine produced a dose-dependent calcium antagonistic effect manifested by depressed indexes of contraction and relaxation. In an autoregulating blood-perfused isolated rabbit heart preparation, nicardipine markedly increased coronary blood flow and slightly decreased systolic pressure at a given end-diastolic pressure. The systolic pressure and +dP/dt versus volume curves, however, were shifted to the left during nicardipine administration, indicating improved systolic function. This increase was accompanied by decreased volume elastance and is probably due, at least in part, to the coronary turgor effect. In humans at rest, intravenous nicardipine administration produced pronounced coronary and systemic vasodilation with improved left ventricular systolic performance and enhanced relaxation accompanied by reflex sympathetic activation. With exercise to ischemia, nicardipine preserved the salutary effects on left ventricular function seen at rest and significantly blunted the increase in left ventricular end-diastolic pressure observed in the control setting. Administration of intracoronary nicardipine to patients produced a slight and transient depression of systolic and diastolic left ventricular function that was accompanied by a pronounced coronary vasodilator response and later by improved ventricular function. This improvement was manifested by decreased end-systolic volume and increased +dP/dt without changes in heart rate, arterial pressure, end-diastolic pressure, or end-diastolic volume. Global diastolic function indexes, including the time constant for isovolumic relaxation, peak filling rate normalized for stroke volume, and volume elastance, were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)