Abstract

The importance of the central nervous system to the antiarrhythmic action of diphenylhydantoin and lidocaine was studied using a cat preparation in which cardiac rhythm changes were produced by electrical stimulation of the posterior hypothalamus. The rhythm change was found to be mediated by the sympathetic nervous system and was characterized by a progressive narrowing of the P-R interval until the P wave disappeared and a junctional rhythm predominated. Recordings from cardiac sympathetic nerves revealed a continuous pattern of hyperactivity during the time of the arrhythmia. Administration of diphenylhydantoin (10-15 mg/kg iv.) prevented both the rhythm disturbance and the hyperactivity in sympathetic nerves. Diphenylhydantoin had no effect on a similar arrhythmia evoked by electrical stimulation of peripheral sympathetic nerves. Administration of lidocaine (2-6 mg/kg i.v.) prevented the arrhythmia produced by hypothalamic stimulation without attenuating hyperactivity of sympathetic cardiac nerves. It also prevented the arrhythmia produced by stimulation of peripheral sympathetic nerves. Results identical to those obtained with lidocaine were observed with methyllidocaine, a quaternary derivative of lidocaine that has difficulty penetrating the blood-brain barrier. These results suggest that the antiarrhythmic action of diphenylhydantoin against neurogenic arrhythmias is due to an action within the central nervous system. The results further suggest, that in contrast to diphenylhydantoin, lidocaine acts at a peripheral neural or cardiac site to antagonize neurogenic arrhythmias.