The Effect of ??-Adrenergic Blockade on the Cardiovascular Response to Diltiazem or Verapamil in Dogs

Abstract

Diltiazem or verapamil were each given at two different infusion rates to pentobarbital-anesthetized dogs with or without a concurrent infusion of propranolol. Changes in cardiovascular function, in reflex activation as reflected by circulating catecholamine levels, and in the chronotropic response to an exogenous beta-adrenergic agonist, isoproterenol, were measured. When administered alone, diltiazem or verapamil, at plasma concentrations of 160 and 370 ng/ml, or 230 and 500 ng/ml, respectively, prolonged atrioventricular conduction and caused systemic vasodilation with a decrease in mean arterial pressure. Cardiac index increased, associated with an increase in arterial norepinephrine level. Heart rate increased with the lower level of verapamil; left ventricular dP/dt increased with both levels of verapamil and at the higher level of diltiazem. Plasma propranolol levels of approximately 35 ng/ml were well tolerated in the absence of diltiazem or verapamil. When added to diltiazem or verapamil, propranolol resulted in an increase in systemic vascular resistance to near control values; a decrease in cardiac index, left ventricular dP/dt, and heart rate; and worsened atrioventricular conduction. Three of nine animals in the high verapamil-propranolol group were unable to maintain a mean arterial pressure greater than 50 mm Hg, and developed a low cardiac index with an elevated systemic vascular resistance, despite very high levels of circulating catecholamines. Compared to the anesthetized state, greater amounts of isoproterenol were needed to effect the same increase in heart rate with the addition of diltiazem, verapamil, or propranolol alone.(ABSTRACT TRUNCATED AT 250 WORDS)