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Cardiovascular profile of the cardioselective beta‐adrenoceptor antagonist bisoprolol in anesthetized pigs
Author(s) -
Verdouw Pieter D.,
Schmeets Iiona O. L.,
Rensen Rob J.
Publication year - 1987
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430110306
Subject(s) - chronotropic , vascular resistance , medicine , bisoprolol , cardiac output , heart rate , blood pressure , stroke volume , anesthesia , vasoconstriction , antagonist , mean arterial pressure , hemodynamics , receptor
The cardioselective beta‐adrenoceptor antagonist bisoprolol ((±)−1‐[4‐(2‐isopropoxyethoxy‐ymethyl)‐phenoxy]3‐isopropylamino‐2‐propanol‐hemifumarate, EMD 33512) was studied for its effects on cardiac performance in ten anesthetized open‐chest pigs. Radioactive labelled microspheres (15 ± 1 μm) were used to determine regional blood flows. In doses of 4, 16, 64, 256, and 1,024 μg · kg −1 (arterial plasma concentrations 1.65 ± 0.07 to 569 ± 22 ng · ml −1 ) 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 hisoprolol (−10%, p < .05). Myocardial it tended to reflected by maxLVdP/dt, fell dose dependetly from 12% (after 4μg · μg·Kg −1 , P < .05) up to 46% (after 1,024 μg · −1 , P < .05). Raising the heart rate to predrug levels revealed that this reduction in maxLVdP/dt 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 vasular resistance increased up to 28% ( P < .05). Pulmonary artery pressure was not affected, because pulmonary vasuclar resistance increased with the highest doses. Left ventricular blood flow, which had already decreased significantly with the lowest dose (11%, P B < .05), also decreased dose dependently (up to 44% after 1,024 μg · kg −1 , 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 O 2 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 beta‐adrenoceptor agents. The finding that no serious adverse cardiovascular affects are observed over a wide dose range warrants further studies in models of myocardial is‐chemia and hypertension.