Noninvasive evaluation of cardiovascular effects of .BETA.-adrenergic blockers with different pharmacological properties.

Abstract

The effects of nadolol (Nad), indenolol (Idn), metoprolol (Met), pindolol (Pid), arotinolol (Art, S-596), and propranolol (Prp) on the cardiovascular system were studied noninvasively in healthy male volunteers. Exercise testing. with a bicycle ergometer was performed both before and after single oral administration of these β-blockers, and any changes in the exercise induced increase in heart rate systolic blood pressure product (ΔDP) were studied. Systolic time intervals were measured from the simultaneous recording of carotid pulse, phonocardiogram, and electrocardiogram at rest. Left ventricular dimensions were measured by echocardiography, and ejection fraction (EF), strokeindex (SI), and cardiac index (CI) were calculated by the standard techniques. Systemic vascular resistance (SVR) was computed from these data. ΔDP was decreased with all β-blockers. According to the degree of this effect, therelative potency of these drugs was estimated to be as follows: Pid > Art> Idn _??_Prp> Nad _??_ Met. The ratio of pre-ejection period to left ventricular ejection time was increased with all β-blockers. EF, SI, and CI were decreased by all β-blockers except Pid, by which SI and CI were kept almost unchanged, and EF was significantly increased. Therefore, Pid was thought to be less cardiosuppressive than the other β-blockers. SVR was significantly decreased by Pid, while it was increased by all the other β-blockers. These results suggest that the acute hemodynamic response to β-blockers is determined primarily by the property of intrinsic sympathomimetic activity. Neither β1-selectivity nor membrane stabilizing effect was shown to be a major factor modifying the central or peripheral hemodynamic response to β-blockers.