Acute hemodynamic and antiischemic properties of intravenous bepridil in coronary artery disease

The acute hemodynamic and antiischemic effects of intravenous bepridil (3 mg/kg/5 minutes followed by 1 mg/kg/hour) were studied in 19 patients with coronary artery disease under basal conditions and during 2 identical pacing stress tests 30 minutes before (pace test I) and 15 minutes after (pace test II) onset of infusion. Bepridil immediately decreased coronary and systemic vascular resistance (26 and 17%, respectively). This resulted in a 19 and 21% reduction in left ventricular systolic and mean aortic pressures and a 15% increase in coronary flow and stroke index (p < 0.05 vs control for each). These vasodilating effects were short lasting, persisting for 5 minutes after the bolus infusion, followed by significant reductions in heart rate (15%) and contractility (10%) and a temporary 46% increase in left ventricular filling pressure. During both pace tests heart rate, contractility, coronary flow and myocardial O 2 consumption were comparable. In contrast, bepridil prevented the significant increase in systemic resistance and mean aortic pressure observed during pace test I (11 and 15%, respectively). Subsequently, myocardial O 2 demand was significantly less during pacing after bepridil, due to an 11% reduction in left ventricular systolic pressure (p < 0.05 vs control and pacing test II vs I). This resulted in marked antiischemic effects: normalization of lactate extraction and reduction in ST-segment depression (−14 ± 7 vs 3 ± 6% and 0.2 ± 0.02 vs 0.13 ± 0.02 mV, respectively, pace test I vs II, p < 0.05), and in less or no angina in 18 patients. Thus, intravenous bepridil significantly reduces acute myocardial ischemia during pacing-induced stress, predominantly through its systemic vasodilating effects and subsequent reduction in myocardial O 2 demand.