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.

Standard microelectrode techniques were used to investigate the in vitro developmental electrophysiologic effects of propafenone and 5-hydroxypropafenone on the adult and neonatal canine Purkinje fiber. The tonic and frequency-dependent depressant effects of these compounds on Vmax and amplitude were similar in both age groups. However, the ability of these compounds to shorten repolarization parameters was more pronounced in the adult. The extent of reduction of abnormal automaticity produced by propafenone was greater in the neonate compared to the adult, and 5-hydroxypropafenone significantly reduced automaticity only in the neonate. The sensitivity of neonatal abnormal automaticity to the effects of these compounds may prove to be important if the use of these agents is to be expanded into the realm of therapy for pediatric automatic rhythms.

Previous data has suggested a deleterious action of Amrinone (Am) on newborn (NB) myocardium. An investigation of the relationship between dose, age, and contractility has been undertaken using isolated right ventricular papillary muscles from NB (0-5 days), juvenile (J) (18-29 days), and adult (A) New Zealand white rabbits. At least six rabbits were studied in each age group using four sequential concentrations of Am (30, 100, 200, 500 mcg/ml). Peak tension (PT), maximum rate of tension development (+dP/dt) and maximum rate of relaxation (-dP/dT) were measured after a fifteen minute equilibration period at each concentration. Repeated measures analysis was used to compare dose response data between age groups. T-tests were used to compare normalized data from the various age groups at a given concentration. Adult heart demonstrated an increase in PT, +dP/dt and -dP/dT with each increase in Am concentration. NB and J heart demonstrated a significant (P<0.05) decrease in PT and +dP/dt for only the lowest dose of An. In contrast to NB the lowest dose did not depress -dP/dT In J. Above 200 mcg/ml, NB and J hearts demonstrated a significant (P<0.05) increase in PT, +dP/dt, and -dP/dt. These results suggest that higher concentrations of Am enhance contractility in NB and J myocardium. While the dose dependence of A heart is monotonic, the NB and J response is biphasic, suggesting multiple and age dependent mechanisms of action. The differential effect of Am on -dP/dT In NB and J hearts implies a developmentally determined action of Am on Ca sequestration in addition to its positive inotropic effect.