Cardiovascular profile of the cardioselective beta‐adrenoceptor antagonist bisoprolol in anesthetized pigs

Abstract

11:187-196, 1987.The cardioselective beta-adrenoceptor antagonist bisoprolol (( f )-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3isopropylamino-2-propanol-hemifumarate, EMD 33512) was studied for its effects on cardiac performance in ten anesthetized open-chest pigs. Radioactive labelled microspheres (15 f 1 pm) were used to determine regional blood flows. In doses of 4, 16, 64, 256, and 1,024 pg. kg-'(arterial plasma concentrations 1.65 0.07 to 569 f 22 ng-ml-') the drug caused dose-dependent decreases in cardiac output (4-31%, P< .05) that were primarily due to a negative chronotropic action as heart rate, which had already been slowed down by 9% (P< .05) after the lowest dose, decreased up to 22% (P < -05). Stroke volume was not significantly affected at any dose, although it tended to decrease after the highest dose of bisoprolol (-lo%, P < .05). Myocardial contractility, reflected by maxLVdP/dt, fell dose dependently from 12% (after 4 pg-pg'kg-', P < .05) up to 46% (after 1,024 pg . kg-' , P < .05). Raising the heart rate to predrug levels revealed that this reduction in maxLVdPldt was not related to the bradycardic action of the drug.Mean arterial blood pressure decreased slightly (< 15%, P < .05) after the highest three doses, but a larger fall was prevented by a mild vasoconstriction of the systemic arterial vascular bed as systemic vascular resistance increased up to 28% (P < .05). Pulmonary artery pressure was not affected, because pulmonary vascular resistance increased with the highest doses. Left ventricular blood flow, which had already decreased significantly with the lowest dose (llO/o, P < .05), also decreased dose dependently (up to 44% after 1,024 pg .kg-', P< .05). These decreases were equally distributed over all myocardial layers as the endolepi blood flow ratio (1.13 0.04) was not affected. Myocardial 0 2 consumption was not affected by the lowest dose, but decreased progressively up to 43% (P < .05) with the higher doses. These changes occurred parallel to those in blood flow as myocardial O2 extraction did change. Cerebral blood flow was well preserved but decreases in perfusion of some other organs and tissues (kidneys, stomach, and skeletal muscle) were similar to those in cardiac output.In conclusion, bisoprolol has a cardiovascular profile similar to that of other betaadrenoceptor agents. The finding that no serious adverse cardiovascular affects are observed over a wide dose range warrants further studies in models of myocardial ischemia and hypertension.