Lidocaine had a significantly greater depressant effect on conduction and accelerated repolarization in adult dogs compared to young dogs, whereas quinidine prolonged repolarization more in the young.
Does the developmental stage (adult vs young) alter the electrophysiologic effects of intravenous lidocaine and quinidine in the canine heart?
The electrophysiologic effects of antiarrhythmic drugs differ significantly between adult and young hearts due to developmental changes in cellular electrophysiology, drug metabolism, and protein binding.
We studied the developmental changes that occur in the use-dependent effects of lidocaine and quinidine on the intact canine heart. At comparable intravenous dosages, adults showed higher total and free plasma lidocaine concentrations than young dogs, whereas for quinidine, the total and free levels were comparable. Lidocaine demonstrated a use-dependent depressant effect on intraventricular conduction in adults that was significantly greater than that in the young, and it significantly accelerated repolarization (QT interval) in the adult. In contrast, comparable effects of quinidine were seen on conduction in adult and young dogs, while repolarization was prolonged more in the young. These effects on conduction and repolarization in the adult and young hearts were explained by our earlier cellular electrophysiologic studies. Our findings indicate the following: (a) developmental changes in the cellular electrophysiologic effects of specific antiarrhythmic drugs are predictive of the effects in the in situ heart; (b) these effects are further modified by developmental differences in drug metabolism and protein binding; (c) developmental changes in the effects of one antiarrhythmic local anesthetic are not necessarily predictive of those for another; and (d) the effects of drugs on the adult heart may be, but are not necessarily, predictive of those in the young.
Morikawa et al. (Thu,) reported a other. Lidocaine and quinidine vs. Adult vs young dogs was evaluated on Use-dependent effects on intraventricular conduction and repolarization. Lidocaine had a significantly greater depressant effect on conduction and accelerated repolarization in adult dogs compared to young dogs, whereas quinidine prolonged repolarization more in the young.