DEVELOPMENTAL ELECTROPHYSIOLOGY OF ENCAINIDE AND ITS MAJOR METABOLITES ON THE PURKINJE-FIBER ACTION-POTENTIAL

Objective. With clinical data suggesting that neonates may be more pro ne to developing electrophysiologic side effects from encainide, this study investigates the in vitro developmental electrophysiologic effec ts of encainide and its major metabolites on the action potential para meters of the canine cardiac Purkinje fiber. Methods. With standard mi croelectrode techniques, the in vitro tonic and rate-related effects o f encainide, and its major metabolites (3-methoxy-4-hydroxy encainide, MODE, and O-dimethhyl encainide, ODE) were investigated using mature and immature canine cardiac Purkinje fibers. Results. The significant developmental differences in the effects of these compounds on the can ine Purkinje fiber illustrated in this study are: (1) 1 x 10(-6) M enc ainide depresses V-max in neonatal Purkinje fibers, yet not in the adu lt. (2) 1 x 10(-6) M MODE lengthens APD(90) in the neonate, yet it has no substantial effect in the adult. (3) 1 x 10(-6) M ODE shortens APD (90) in the adult, yet it has no appreciable effect on the neonate. (4 ) Rate-related effects of encainide and ODE are more pronounced in adu lt Purkinje fibers. Conclusion. In contrast to other in vitro studies on class I antiarrhythmic agents, neonatal canine Purkinje fibers seem to be more sensitive than the adult to the tonic depolarization depre ssant effect of encainide. This in vitro sensitivity parallels clinica l experience with the drug in neonatal patients. Although encainide is no longer available for clinical use, these findings highlight the fa ct that the immature conduction system may show markedly different sen sitivities to different class I agents despite the fact that these age nts share similar qualitative pharmacologic properties.