HEMODYNAMIC-EFFECTS OF A NEW CALCIUM-ANTAGONIST, SR-33557, IN PATIENTS WITH CORONARY-ARTERY DISEASE AND NORMAL LEFT-VENTRICULAR FUNCTION

SR 33557 is a new calcium antagonist which in vitro demonstrated selec tivity for smooth muscle over cardiac muscle. To assess the hemodynami c effects of SR 33557 in humans, SR 33557 was administered intravenous ly (i.v.) in 9 patients with normal systolic left ventricular function [LV ejection fraction (EF)=63.7+/-8%] undergoing right and left cathe terization. Baseline measurements were recorded before and during righ t 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 wer e evident from discontinuation of the infusion, maximal between the te nth and twentieth min after discontinuation of the infusion. Without a trial pacing, the main effect of SR 33557 infusion was to decrease hea rt rate (HR) from 77.7+/-10.7 to 61.9+/-9.3 beats/min (p<0.001). Cardi ac 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 (MA P) decreased from 104.7+/-29.6 to 94.3+/-22.9 mm Hg (p<0.05) with no c hange in filling pressures or systemic vascular resistance (SVR). Cons equently, rate-pressure product (RPP) decreased from 8,211+/-3,092 to 5,906+/-2,025 mm Hg.beat(-1) (p<0.01). Peak positive LVdP/dt decreased from 1,711+/-257 to 1,533+/-194 (p<0.01). During the pacing phase, no ne of the hemodynamic parameters differed from baseline; especially pe ak positive LVdP/dt remained unchanged. SR 33557 has negative chronotr opic action but shows no direct negative inotropic effect in patients with normal systolic LV function.