Hemodynamic Effects of a New Calcium Antagonist, SR 33557, in Patients with Coronary Artery Disease and Normal Left Ventricular Function

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Abstract

Summary

SR 33557 is a new calcium antagonist which in vitro demonstrated selectivity for smooth muscle over cardiac muscle. To assess the hemodynamic effects of SR 33557 in humans, SR 33557 was administered intravenously (i.v.) in 9 patients with normal systolic left ventricular function [LV ejection fraction (EF) = 63.7 ± 8%] undergoing right and left catheterization. Baseline measurements were recorded before and during right atrial pacing (100 beats/min), after which 5 mg SR 33557 was infused in 10 min and hemodynamic parameters were continuously recorded until 30 min after discontinuation of the infusion. Effects of SR 33557 were evident from discontinuation of the infusion, maximal between the tenth and twentieth min after discontinuation of the infusion. Without atrial pacing, the main effect of SR 33557 infusion was to decrease heart rate (HR) from 77.7 ± 10.7 to 61.9 ± 9.3 beats/min (p < 0.001). Cardiac index (CI) did not change; stroke volume index (SVI) increased from 44.2 ± 13 to 50.4 ± 15 ml · m-2, (p < 0.05). Mean arterial pressure (MAP) decreased from 104.7 ± 29.6 to 94.3 ± 22.9 mm Hg (p < 0.05) with no change in filling pressures or systemic vascular resistance (SVR). Consequently, rate-pressure product (RPP) decreased from 8,211 ± 3,092 to 5,906 ± 2,025 mm Hg beat-1 (p < 0.01). Peak positive LV dP/dt decreased from 1,711 ± 257 to 1,533 ± 194 (p < 0.01). During the pacing phase, none of the hemodynamic parameters differed from baseline; especially peak positive LV dP/dt remained unchanged. SR 33557 has negative chronotropic action but shows no direct negative inotropic effect in patients with normal systolic LV function.

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