Relation between serum nifedipine concentration and hemodynamic effects in nonobstructive hypertrophie cardiomyopathy

Abstract

The relation between nifedipine concentration and hemodynamic effects after sublingual administration of 10 or 20 mg was examined in 13 patients with nonobstructive hypertrophie cardiomyopathy (HC). Serum nifedipine concentrations were determined by gas chromatography and were not related to dose. Peripheral vascular resistance decreased as a function of nifedipine concentration (r = −0.63, p < 0.001); this was associated with a concentration-related increase in heart rate (r = 0.56, p < 0.001) and in cardiac index (r = 0.50, p < 0.001). However, evidence for a pure vasodilator effect of nifedipine was inconsistent, in that the change in stroke volume index with nifedipine was not significant. Although stroke volume index increased at nifedipine concentrations between 60 and 120 ng/ml (38 ± 6 to 42 ± 4 ml/m 2, p < 0.01), it decreased at concentrations >120 ng/ml (40 ± 3 to 38 ± 4 ml/m 2, p < 0.01). Moreover, pulmonary artery wedge pressure increased at nifedipine concentrations >120 ng/ml (11 ± 2 to 16 ± 4 mm Hg, p < 0.001), suggesting either depressed left ventricular (LV) systolic function or reduced LV filling. To investigate these possible mechanisms, LV systolic and diastolic function was studied during catheterization with a nonimaging scintillation probe in 6 of the 13 patients. In these subjects, heart rate was held constant by atrial pacing. Nifedipine, at concentrations ≤120 ng/ml did not alter end-diastolic volume, but increased LV stroke volume and ejection fraction; concentrations >120 ng/ml were associated with increased end-diastolic and end-systolic volumes, reduced ejection fraction and end-systolic pressure-volume ratio. No beneficial effects on LV diastolic function were observed at these higher concentrations, as the time constant of isovolumic relaxation increased (32 ± 13 to 60 ± 11 ms, p < 0.01). These results indicate that the hemodynamic effects of nifedipine are related closely to nifedipine concentration in patients with nonobstructive HC. Peripheral vasodilating effects are evident over a wide range of nifedipine levels. At low and medium concentrations, these effects result in augmentation of LV ejection performance; however, negative inotropic effects predominate at high concentrations.