Developmental changes in the effects of lidocaine on the electrophysiological properties of canine Purkinje fibers.

Abstract

Developmental changes in the cardiac effects of antiarrhythmic drugs have been noted in the clinical setting. To study whether these might in part be based on developmental differences in drug effects on the transmembrane potential, we used standard microelectrode techniques to study the effects of lidocaine on the transmembrane potentials of Purkinje fibers from adult and young dogs. Control studies of membrane responsiveness and steady state recovery kinetics of Vmax showed no age-related differences in these variables. Lidocaine reduced Vmax of adult fibers to a greater extent than that of young fibers at basic drive cycle lengths of 1000 and 400 msec. The number of beats to reach steady state Vmax at basic drive cycle length of 400 msec was smaller in adult than in young fibers. Both tonic and use-dependent block appeared to be greater and to develop more rapidly in the adult than the young fibers. Moreover, fibers from young dogs recovered more rapidly from the effects of lidocaine than did adult fibers. These data suggest there are developmental changes in the tonic and use-dependent effects of lidocaine that may contribute to age-related differences in drug effect.