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

Abstract

The effects of several beta-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 beta-adrenoceptor blockade was also assessed. All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac beta-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective beta-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 beta-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 postischaemic arrhythmias is blockade of cardiac beta-adrenoceptors.