Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.

To investigate the mechanisms of ventricular arrhythmia sup- pression by propranolol, we determined the antiarrhythmic ef- ficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-proprano- lol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (> 80% VED reduc- tion), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858681). For the entire group, the QTc interval shortened by 44% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta- blockade, racemic propranolol was then administered in dos- ages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was ef- fective via a non-beta-mediated action. By contrast, in 5/8 pa- tients racemic propranolol also suppressed VEDs. We con- clude that propranolol suppresses ventricular arrhythmias by both beta-and non-beta-adrenergic receptor-mediated effects. (J. Clin. Invest. 1990 .85:836-842.) propranolol * antiarrhyth- mic * ventricular arrhythmias * dextropropranolol-beta- adrenergic receptor blockade Introduction Although propranolol has been used clinically in the United States for over 20 years, its mechanism(s) of action are not fully understood. Recently in the Beta-blocker Heart Attack Trial (BHAT), propranolol was found to reduce mortality after acute myocardial infarction (1). Since other beta receptor an- Deceased.