Changes in regional blood flows and myocardial performance after administration of bisoprolol to pigs

Abstract

The cardioselective beta-adrenoceptor antagonist bisoprolol (4-1024 micrograms kg-1) caused in anaesthetized open-chest pigs a dose-dependent decrease in cardiac output, which was primarily due to a negative chronotropic action as heart rate decreased more than stroke volume. The decrease in stroke volume apparently resulted from a negative inotropic action of the drug, reflected by a decrease in max LV dP/dt in animals both with and without atrial pacing. A mild increase in systemic vascular resistance prevented serious hypotension. Pulmonary artery pressure was not affected, as pulmonary vascular resistance increased although the increase was statistically significant only with the highest concentration. The dose-related decreases in left ventricular blood flow were equally distributed over all myocardial layers and were the consequence of the reduced metabolic needs of the myocardium. Cerebral blood flow was well preserved but the changes in blood flow to some other organs and tissues (kidneys, stomach and skeletal muscle) paralleled that in cardiac output. The systemic haemodynamic effects of bisoprolol (16-1024 micrograms kg-1; i.v.) in conscious pigs resembled closely those observed in anaesthetised animals and were similar to those exerted by propanolol (25-300 micrograms kg-1; i.v.) in the same preparation. The effectiveness of bisoprolol and propranolol in antagonizing isoprenaline-induced changes in heart rate and max LV dP/dt were, however, markedly different. While propranolol inhibited both parameters to the same extent, bisoprolol was more effective in inhibiting max LV dP/dt than heart rate responses in conscious animals, probably due to beta 1-adrenoceptor selectivity.