HEMODYNAMIC PROPERTIES OF BUCINDOLOL, A BETA-ADRENOCEPTOR BLOCKING DRUG WITH VASODILATOR ACTIVITY

Bucindolol is a new nonselective β-adrenergic blocking agent with direct vasodilator, partial agonist and α-adrenergic blocking properties. Its hemodynamic effects were evaluated in 13 healthy young men. In an open study, the effects of increasing single oral doses (50 to 200 mg) were examined. Two hours after each dose there was little effect at rest, but the responses of heart rate and systolic blood pressure to cycle exercise (50 to 150 W) were significantly reduced. There was no greater effect with larger doses. The second phase was a 3-way double-blind study comparing the effects of placebo with 50 and 200 mg of bucindolol. Left ventricular (LV) ejection phase indexes derived from digitized M-mode echocardiograms (% fractional shortening, mean and peak velocity of circumferential fiber shortening, stroke volume) increased more than 10% 2 and 4 hours after bucindolol was administered, whereas systemic vascular resistance and the ratio preejection period/LV ejection time decreased to the same extent. Although there was little effect on measurements at rest, the response to cycle exercise of heart rate and systolic blood pressure were significantly attenuated. These results show that the effects of bucindolol on LV systolic function are related at least in part to reduction of afterload, but do not indicate whether the drug has an additional direct inotropic effect