ELECTROPHYSIOLOGICAL EVALUATION OF THE SODIUM-CHANNEL BLOCKER CARBAMAZEPINE IN HEALTHY-HUMAN SUBJECTS

Carbamazepine (CBZ) is a sodium-channel blocker used mainly for the tr eatment of epileptic seizures and neuralgias. It may impair the functi on of the cardiac conduction system in susceptible patients, but its e lectrophysiological effects have not been thoroughly assessed in the n ormal heart, which was the aim of the present study. Ten healthy volun teers, mean age 32 years, underwent two electrophysiological investiga tions at baseline and three at different dose levels of CBZ. The trans esophageal atrial stimulation technique was used to evaluate sinus nod e function, refractoriness of the atrial myocardium, atrioventricular conduction, and ventricular depolarization and repolarization (as refl ected by the QRS, JT, and QT intervals) at spontaneous rhythm and afte r atrial pacing. Atropine was administered to facilitate 1:1 conductio n and assessment of rate-dependent effects. At the highest CBZ dose (8 00 mg/day), which gave plasma concentrations within the upper therapeu tic range, the PQ interval was mildly prolonged (151 vs. 159 msec; p < 0.01). In addition, the shortening of the JT interval normally seen a t higher pacing rates was counteracted by high-dose CBZ, as demonstrat ed by a lower mean slope of the regression line after atropine and CBZ than after atropine alone (0.17 vs. 0.20; p < 0.05). No other effects were detected. At therapeutic levels CBZ had minimal effects on the h ealthy conduction system, supporting its safe use in the absence of ca rdiac disease.