Differential hemodynamic effects of beta-adrenoceptor blockers, Ca antagonists and combined alpha-beta-receptor blockade in ischemic heart disease.

Abstract

The hemodynamic responses to 3 different therapeutical regimens: beta-adrenoceptor blockade, calcium inflow inhibition and combined alpha-beta-blockade were evaluated in 3 matched randomized groups of patients with ischemic heart disease and typical exercise-induced angina. The groups consisted of 22, 16 and 15 men, mean age 55-59 years. They were studied at rest and during ischemia-inducing exercise, before and after single oral doses of 100 mg metoprolol, 10 mg nifedipine and 200 mg labetalol. Pressures in the brachial artery and the pulmonary circulation were recorded by means of percutaneously introduced catheters. Cardiac output was determined according to the Fick principle. Metoprolol reduced mean arterial pressures, heart rate and cardiac output. Systemic vascular resistance and left ventricular filling pressure increased. Nifedipine resulted under all conditions in a distinct reduction of systemic vascular resistance and arterial pressures and a slight increase in heart rate and cardiac output. Left ventricular filling pressure was significantly lowered, the more the higher the initial level. The effect of labetalol was similar to that of nifedipine; however, cardiac output was unchanged and heart rate was slightly reduced. Left ventricular filling pressure was significantly lower. It is apparent that suppression of adrenergic stimulation by beta-receptor blockade alone may have adverse hemodynamic effects in ischemic heart disease and prompt further functional deterioration. Conversely, both calcium and combined alpha-beta-receptor blockade tend to improve left ventricular function by lowering both left ventricular preload and total systemic vascular resistance. The results strongly suggest that in patients in whom beta-receptor blockers appear indicated, their adverse hemodynamic effects can be offset by concomitant alpha1-receptor blockade or vasodilation without losing symptomatic efficacy. Combined alpha-beta-receptor blockade has the advantage over calcium antagonists alone to prevent any increase in adrenergic activity and related hyperkinetic response.