The effect of β-adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

C. A. Campbell, J. Parratt

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Abstract

The effects of several β-adrenoceptor blocking agents, ((+), (-) and (±)-oxprenolol, p-oxprenolol, practolol, propranolol and timolol) were investigated on the ventricular arrhythmias occurring within the first 30 min of acutely ligating the main left coronary artery in anaesthetized rats. The degree of cardiac and vascular β-adrenoceptor blockade was also assessed. All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac β-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective β-adrenoceptor blocking agents. A comparison of the two isomers of oxprenolol demonstrated that the (-)-isomer markedly suppressed ischaemic arrhythmias (ventricular ectopic beats, incidence and duration of ventricular tachycardia and duration of ventricular fibrillation) more effectively than the (+)-isomer. Compounds possessing intrinsic sympathomimetic activity (ISA) caused less marked haemodynamic changes (in equivalent β-blocking doses) than those that did not possess this ancillary property. The membrane stabilizing activity of oxprenolol and p-oxprenolol did not appear to contribute to the antiarrhythmic activity of these agents; however, the membrane stabilizing activity of propranolol may contribute to its effectiveness. In all the drugs studied, the main pharmacological property required to suppress early post-ischaemic arrhythmias is blockade of cardiac β-adrenoceptors.

Original languageEnglish
Pages (from-to)939-946
Number of pages8
JournalBritish Journal of Pharmacology
Volume79
Issue number4
Publication statusPublished - 1983

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Oxprenolol
Adrenergic Receptors
Ligation
Cardiac Arrhythmias
Coronary Vessels
Practolol
Propranolol
Timolol
Sympathomimetics
Ventricular Premature Complexes
Membranes
Ventricular Fibrillation
Ventricular Tachycardia
Blood Vessels
Hemodynamics
Pharmacology
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

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abstract = "The effects of several β-adrenoceptor blocking agents, ((+), (-) and (±)-oxprenolol, p-oxprenolol, practolol, propranolol and timolol) were investigated on the ventricular arrhythmias occurring within the first 30 min of acutely ligating the main left coronary artery in anaesthetized rats. The degree of cardiac and vascular β-adrenoceptor blockade was also assessed. All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac β-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective β-adrenoceptor blocking agents. A comparison of the two isomers of oxprenolol demonstrated that the (-)-isomer markedly suppressed ischaemic arrhythmias (ventricular ectopic beats, incidence and duration of ventricular tachycardia and duration of ventricular fibrillation) more effectively than the (+)-isomer. Compounds possessing intrinsic sympathomimetic activity (ISA) caused less marked haemodynamic changes (in equivalent β-blocking doses) than those that did not possess this ancillary property. The membrane stabilizing activity of oxprenolol and p-oxprenolol did not appear to contribute to the antiarrhythmic activity of these agents; however, the membrane stabilizing activity of propranolol may contribute to its effectiveness. In all the drugs studied, the main pharmacological property required to suppress early post-ischaemic arrhythmias is blockade of cardiac β-adrenoceptors.",
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