Negative inotropic effect of intravenous nifedipine in coronary artery disease: Relation to plasma levels

The relative extent of the vasodilator versus direct negative inotropic effects of nifedipine wasstudied in 15 male patients with documented coronary artery disease and normal left ventricular function. At the time of diagnostic cardiac catheterization, three groups of five patients received doses of 1, 2, and 3 mg intravenous nifedipine at a rate of 0.33 mg/min. Hemodynamic measurements and blood collections were made before, during, and every 5 minutes for 30 minutes after infusion of nifedipine. Heart rate increased and mean arterial pressure decreased significantly after the 2 and 3 mg doses of nifedipine. Systemic vascular resistance was significantly decreased and cardiac index increased after all doses of nifedipine. Maximal left ventricular dp/dt (dp/dt_max) was significantly decreased after the 3 mg infusion. The reduction in dp/dt_max was most consistent with a reduction in left ventricular contractility as opposed to changes in loading conditions. Plasma concentrations of nifedipine were significantly correlated with bidirectional changes in dp/dt_max (r=0.86). Nifedipine concentrations below 28.2 ng/ml were associated with a rise in dp/dt_max, whereas concentrations above that level were associated with a reduction in dp/dt_max. These data indicate that intravenous nifedipine produces dose- and concentration-dependent depression of myocardial contractility in patients with coronary artery disease. Nifedipine concentrations associated with negative inotropic effects are readily achievable with common oral and sublingual doses.