On the cardiovascular and antiarrhythmic actions of the cardioselective beta‐adrenoceptor antagonist bevantolol in the pig

Hartog, J. M.; Bremen, Robert H. Van; Verdouw, Pieter D.

doi:10.1002/ddr.430070103

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…Beta-adrenoceptor antagonists usually decrease cardiac output by negative chronotropic and inotropic actions. This study shows that when the reduction in heart rate is related to that in maxLVdPldt, bisoprolol behaves very similarly to some other beta-adrenoceptor antagonists such as bevantolol (cardioselective) and propranolol (noncardioselective), which have been evaluated in the same model [Wolffenbuttel and Verdouw, 1983;Hartog et al, 1986;Verdouw et al, 19861. In the present study heart rate had only a minor effect on maxLVdP/dt, which is in agreement with the results reported earlier for the same species [Scheffer and Verdouw, 19831. This implies that the decrease in maxLVdP/dt mainly reflects a decrease in myocardial contractility, because the changes in pre-and afterload were of minor importance. Since autonomic cardiac innervation was preserved, we cannot conclude whether this decrease in maxLVdP/dt was the result of a direct myocardial depressant effect, or the result of inhibition of the sympathimometic activity, or (most probably) a combination of both.…”

Section: Systemic Hemodynamicsmentioning

confidence: 93%

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

Verdouw

Schmeets

Rensen

1987

Drug Development Research

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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.

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Section: Systemic Hemodynamicsmentioning

confidence: 93%

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

Verdouw

Schmeets

Rensen

1987

Drug Development Research

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The effects of dietary mackerel oil on plasma and cell membrane lipids, on hemodynamics and cardiac arrhythmias during recurrent acute ischemia in the pig

1986

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Fish-oil nutrition leads to a change in fatty acid composition of cellular membranes. To investigate whether this affects cardiac responses to acute myocardial ischemia, pigs were fed a 9.1% (w/w) mackerel-oil (n = 8) or 9.1% (w/w) lard-fat diet (n = 8). Eight weeks mackerel-oil feeding reduced plasmacholesterol (51%) and triglyceride (48%), while the n-6 fatty acids of cardiac and platelet membrane phospholipids were partially replaced by n-3 fatty acids. After 8 weeks the animals were anesthetized and the left anterior descending coronary artery was occluded 6 times for a period of 5 min at 15 min intervals. Recovery of cardiac function and the incidence of cardiac arrhythmias were similar for both dietary groups. However, during the last reperfusions, hyperemic responses were less in magnitude and shorter lasting in the lard-fat (81 +/- 17 ml/min) than in the mackerel-oil group (129 +/- 18 ml/min). This may be caused by a difference in thromboxane synthesis, as coronary venous blood thromboxane B2 levels were higher in the lard-fat (77 +/- 6 pg/ml) than in the mackerel-oil group (19 +/- 7 pg/ml, P less than 0.05) during peak hyperemia. The low baseline levels of both thromboxane B2 and 6-keto prostaglandin F1alpha in fish-oil fed animals originate from the reduced content of precursor fatty acid in the membrane phospholipids. In conclusion, despite marked changes in membrane fatty acid composition induced by prolonged feeding with fish oil, no modification of recovery of cardiac function and of incidence of cardiac arrhythmias was found during acute recurrent ischemia.

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Systemic and regional hemodynamic, antiarrhythmic and antiischemic effects of bevantolol in anesthetized pigs

Verdouw

Hartog

Saxena

et al. 1986

The American Journal of Cardiology

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On the cardiovascular and antiarrhythmic actions of the cardioselective beta‐adrenoceptor antagonist bevantolol in the pig

Cited by 3 publications

References 27 publications

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

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

The effects of dietary mackerel oil on plasma and cell membrane lipids, on hemodynamics and cardiac arrhythmias during recurrent acute ischemia in the pig

Systemic and regional hemodynamic, antiarrhythmic and antiischemic effects of bevantolol in anesthetized pigs

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