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

Abstract

The effects of several P-adrenoceptor blocking agents, ((+), (-) and (±)-oxprenolol, poxprenolol, 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 3-adrenoceptor blockade was also assessed. 2 All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac P-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective 3-adrenoceptor blocking agents. 3 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. 4 Compounds possessing intrinsic sympathomimetic activity (ISA) caused less marked haemodynamic changes (in equivalent f-blocking doses) than those that did not possess this ancillary property.5 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. 6 In all the drugs studied, the main pharmacological property required to suppress early postischaemic arrhythmias is blockade of cardiac f-adrenoceptors.

Effects of morphine on catecholamine release and arrhythmias evoked by myocardial ischaemia in rats

“…Ventricular fibrillation or tachycardia were seen only during the first 15 min. These observations are also in agreement with those of other investigators using the same model (Clark et al, 1980;Marshall et al, 1981;Au et al, 1983;Campbell & Parratt, 1983). Our finding of a total of 614 ± 166 VES during the first 30 min of ischaemia is lower than that reported by some other groups of workers.…”

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat

“…In acutely prepared anaesthetized rats we found propranolol to have very weak antiarrhythmic activity (Au et al, 1983), although others have demonstrated more powerful antiarrhythmic effects with P-blockers in anaesthetized animals (Campbell & Parratt, 1983). …”

The effects of the combined administration of β‐adrenoceptor antagonists and non‐steroidal anti‐inflammatory drugs on ligation‐induced arrhythmias in rats

“…Propranolol (1 and 5 mg kg-) prevented ventricular fibrillation. Other P-adrenoceptor blockers have also been shown to be protective in the dog, cat, rat and man (Grayson et al, 1968;Reimer et al, 1973;Jennings & Reimer, 1979;Khan et al, 1972;Campbell & Parratt, 1983). This protective effect has been shown to be dose-related and due solely to Padrenoceptor blockade since the L-isomers were more effective than the D-isomers (Parratt et al, 1983).…”