Antiarrhythmic efficacy of propranolol: comparison of low and high serum concentrations

Propranolol has been effective in suppressing ventricular arrhythmias in up to 70% of patients in some series; however, a wide range of concentrations was required to produce this degree of efficacy. In one series, 40% of responders required high serum concentrations (greater than 500 ng/ml) in excess of those required for physiologic beta-receptor blockade (25 to 150 ng/ml). To assess the relative contribution of high concentration electrophysiologic effects to antiarrhythmic efficacy the results of programmed electrical stimulation were compared at high and low (beta-blocking) concentrations in 28 patients with inducible sustained ventricular tachycardia. Propranolol was given as a series of loading and maintenance infusions producing first a mean concentration of 130 +/- 72 ng/ml (beta-blocking) and then a mean concentration of 743 +/- 523 ng/ml (high). Beta-blockade was assessed by the percent reduction in exercise-induced tachycardia. Near maximal beta-blockade was achieved by a concentration of 150 ng/ml. At a low concentration, 6 of 28 patients had a response to propranolol (complete in 5 and partial in 1). At a high concentration, one additional patient had a complete response while three had a partial antiarrhythmic response. At high concentrations of propranolol there was a significant shortening of the QTc interval relative to that seen during the low dose infusion. No other significant electrophysiologic changes occurred at high versus low concentration. In summary, an antiarrhythmic response to propranolol occurs most frequently at a beta-blocking concentration. High concentration electrophysiologic effects occur and these appear to contribute to antiarrhythmic efficacy in some patients.