Using standard microelectrode techniques, the developmental cellular electrophysiologic effects of moricizine HCl on adult and neonatal canine Purkinje fibers were studied. Steady state and rate-related changes in the transmembrane action potentials produced by moricizine HCl in both age groups were characterized and compared. Also, the rate of barium-induced abnormal automaticity before and after drug was also investigated in neonatal and adult Purkinje fibers. The major findings of this study are as follows. (1) The steady state and rate-related depressant effects of moricizine HCl on Vmax were similar in both age groups. (2) Moricizine HCl shortened APD90 in the adult fibers to a greater extent than in the neonate. (3) The concentration of moricizine HCl required to significantly reduce the rate of abnormal automaticity was less in the neonate than in the adult. The effect of moricizine HCl on APD90 of individual Purkinje fibers is influenced both by their control APD90 value as well as by maturational factors. It is less clear whether developmental differences in the effects of moricizine HCl on abnormal automaticity are solely a result of differences in control rates of abnormal automaticity between the two age groups.

Transmembrane recordings and surface electrograms were used to evaluate the influence of propafenone on the cellular electrophysiology of isolated neonatal and adult rabbit atrioventricular node (AVN) preparations. An automatic interval of 863 +/- 82 ms (mean +/- SEM, n = 14) in neonates was found to be significantly shorter than the 1510- +/- 205-ms (n = 12) automatic interval observed in adults. Propafenone in a concentration of 5 x 10(-6) M significantly increased the automatic interval of neonatal pacemakers but not that of the adult preparations. These changes in automaticity produced by propafenone were not dependent on the adrenergic receptor-blocking action of the drug. The pacemaker escape time after overdrive pacing was also shorter in the neonate than in the adult. Propafenone prolonged the escape time of the neonatal tissues but not those of the adult. AVN refractory period, A-H interval, and antegrade Wenckebach rate were comparably increased in a concentration-dependent manner in both age groups. The maximum diastolic potential was decreased by propafenone in the neonatal atrionodal tissue but not in other regions of the AVN and not in any region of the adult AVN. Action-potential duration was increased in all regions of the AVN in both age groups. Action-potential amplitude and maximum upstroke velocity were decreased by propafenone in both age groups. Unlike other excitable tissues of the heart, the action-potential duration of AVN nodal cells increased with decreasing pacing intervals as the pacing interval approached the Wenckebach interval.(ABSTRACT TRUNCATED AT 250 WORDS)