A comparison of the effects of (±)-propranolol and (+)-propranolol in anaesthetized dogs; β-receptor blocking and haemodynamic action

Abstract

The adrenergic β-receptor blocking activities of (±)-propranolol and (+)-propranolol have been compared in anaesthetized dogs, using isoprenaline as the agonist. (+)-Propranolol possessed less than one fiftieth the potency of (±)-propranolol. Intravenous (±)-propranolol (0·25 mg/kg) produced a six-fold increase in the isoprenaline dose ratio and significantly lowered heart rate, cardiac contractile force, ejection rate and tension time index. The same dose of (+)-propranolol had no effect on the isoprenaline dose ratio nor did it significantly alter these haemodynamic variables. Since both isomers of propranolol have equivalent membrane stabilizing properties it was concluded that the haemodynamic effects of (±)-propranolol at this dose level were due to specific β-blockade and not to any “quinidine-like” properties. Higher doses of (+)-propranolol (1·25 mg/kg) significantly reduced heart rate and cardiac contractile force whilst increasing atrio-ventricular conduction time without raising the threshold to isoprenaline. There was no effect on ejection time, mean ejection rate or tension time index. Extremely high doses of (+)-propranolol slightly raised the isoprenaline dose ratio in intact dogs but not after vagal section. The arithmetic difference between the effects of equivalent doses of (±)-propranolol and (+)-propranolol was approximately constant. The findings suggest that (±)-propranolol reduces cardiac work by blocking the sympathetic drive to the heart at doses up to 0·2 mg/kg (the usual clinical dose range) and that direct depression of the mycardium only occurs at doses well above this.