Nicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 ± 13 μg/min) and nicardipine (mean dose 5.2 ± 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 ± 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion.Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 ± 2 to 14 ± 2 mm Hg, p < 0.01) than with nicardipine (27 ± 2 to 23 ± 3 mm Hg, p < 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 ± 0.1 to 2.1 ± 0.1 liters/min per m2(p < 0.05) with nitroprusside and to a greater extent from 1.7 ± 0.1 to 2.4 ± 0.1 liters/min per m2(p < 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 ± 0.01 to 0.19 ± 0.01, p < 0.01), but not with nitroprusside.Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents. Left ventricular pressure-volume loops were constructed for 14 patients. In 12 patients, the left ventricular end-systolic pressure-volume relation was shifted rightward with nicardipine, indicating a negative inotropic effect, with no shift in the remaining 2 patients.Thus, nicardipine has a negative inotropic effect in patients with heart failure. Despite this effect, left ventricular ejection fraction and cardiac index increased with nicardipine. This overall improvement in ventricular systolic performance was due to a reduction in afterload.
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