The haemodynamic effects of (±)-propranolol, dexpropranolol, oxprenolol, practolol and sotalol in anaesthetised dogs

Abstract

The effects of cumulative i.v. doses of the β-blocking drrugs practonol, oxprenolol, sotalol, (±)-propanolol and dexpropranolol upon dP dt , left ventricular strain gauge measurements and atrioventricular conduction times have been determined at fixed rates in open-chested vagotomized normal and catecholamine-depleted dogs. Practolol, oxprenolol, sotalol and (±)-propranolol, in doses between 0.1 and 2.56 mg/kg, caused dose-dependent reductions in dP dt and strain gauge measurements and an increase in conduction time. When these drugs were administered in the same dose range to catecholamine-depleted dogs, (±)-propranolol and sotalol did not alter these parameters from control values, whilst oxprenolol and practolol decreased conduction time and increased dP dt and strain gauge measurements. Dexpropranolol, 0.01–2.56 mg/kg, had no effect on dP dt , strain gauge measurements or conduction time in normal or catecholamine-depleted dogs. In doses greater than 2.56 mg/kg, oxprenolol, sotalol and (±)-propranolol caused further increases in conduction time and decrease in dP dt and strain gauge measurements in both normal and catecholamine-depleted dogs. Dexpropanolol in doses greater than 2.56 mg/kg also caused similar changes. In contrast, practolol, in doses up to 82 mg/kg, caused no changes in these parameters additional to those observed at lower doses in either normal or catecholamine-depleted dogs. It is concluded that the initial decreases in dP dt and strain gauge measurements and increase in conduction time caused by low doses of practolol, oxprenolol, sotalol and (±)-propranolol aree due to adrenergic β-receptor blockade. The increase in dP dt , strain gauge measurements and decrease in conduction time in catecholamine-depleted dogs caused by practolol and oxprenolol are due to the intrinsic sympathomimetic activity of these drugs. Further decreases in dP dt and strain gauge measurements, and increase in conduction time after high doses of oxprenolol, sotalol (±)-propranolol and dexopropranolol in both normal catecholamine-depleted dogs indicate that these drugs also have membrane-stabilizing properties. Practolol was shown not to have membrane-stabilizing properties in doses up to 82 mg/kg. The technique described may be useful in relating the additional properties of β-blocking agents to their adrenoceptive blocking actions.