Beta-adrenergic blockade and antiarrhythmic activity of (-)- and (+)-propranolol

Abstract

Beta-blockade potency and antiarrhythmic activity of the (+) and (—) isomers of propranolol were compared in anesthe­tized dogs. Dose-response curves for the tachycardia induced by isoproterenol were obtained. Cardiac arrhythmias (ventricu­lar tachycardia) were induced by i.v. oua­bain. (—)-Propranolol was more potent beta blocker than (+)-propranolol; only (—)-propranolol, at high doses, reversed the depressor response to isoproterenol. Beta-blocking doses of (—)-propranolol produced temporary reversion of the ven­tricular tachycardia, and high doses pro­duced permanent reversion in 5 out of 6 dogs. On the other hand, (4-)-propranolol succeeded only in 2 out of 6 dogs. AV blockade consistently accompanied the si­nus rhythm restoration, but was more se­vere in the dextro isomer series. It is con­cluded that, in these experimental arrhyth­ mias, beta-blockade seems to play an important role in determining the antiarrhythmic effectiveness of the drug, by inhibiting the sensitizing action of the adrenergic outflow on the ouabain-intoxicated heart.