[Electrophysiological study on mexiletine in man with reference to dose-response relation]

The electrophysiological properties of Mexiletine were investigated by endocavitary His Bundle recording and programmed electrical stimulation of the heart in 30 patients. Differing dosage (2, 2.7 and 3.4 mg/kg) were given intravenously in 3 groups of 10 patients. The effects on the length of the sinus cycle, conduction intervals and cardiac refractory periods were observed and the following results obtained : 1. Sinus rhythm increased at all dosages but this effect was much more pronounced with 3.4 mg/kg dosage (--12.8% +/- 2.81% : : % shortening of sinus cycle with respect to the basal cycle +/- SD, p less than 0.005); 2. Atrioventricular nodal conduction time (A-H interval) decreased, the effect being more marked with the larger dose regimes; 3.His-Pirkinje conduction time (H-V interval) unaltered except in 3 cases where it increased by 5 ms after injection of 2.7 mg/kg; 4. Relative refractory period of His-Parkinje system shortened, this effect also being more pronounced with the larger doses ( --3.75 +/- 0.25% :2.7 mg/kg, p less than 0,001; -- 7 +/- 1.46% 3.4 mg/kg, p less than 0.005). In conclusion, the changes observed in the His-Purkinje system after mexiletine were similar to those of Lignocaine and Diphenylhydantoin. The drug also appears to have a marked vagal inhibitory effect as shown by the acceleration of the sinus rhythm and reduced atrioventricular conduction times.