Effect of diphenylhydantoin and lidocaine on cardiac arrhythmias induced by hypothalamic stimulation.

The importance of the central nervous system in the antiarrhythmic actions of diphenyhiydantoin and lidocaine was studied using arrhythmias induced by electrical stimulation of the posterior hypothalamus in cats. Hypothalamic stimulation resulted in cardiac arrhythmias mediated by the sympathetic nervous system. The arrhythmias occurred during stimulation, and recordings from cardiac sympathetic nerves revealed a continuous pattern of hyperactivity during the time of the arrhythmia. Administration of diphenylhydantoin (10-15 mg/kg I.V.) prevented both the arrhythmias and the hyperactivity in sympathetic nerves. Diphenylhydantoin had no effect on similar arrhythmias evoked by electrical stimulation of peripheral sympathetic nerves. Administration of lidocaine (2-6 mg/kg I.V.) prevented the arrhythmias produced by hypothalamic stimulation without attenuating sympathetic hyperactivity, and also prevented similar arrhythmias produced by stimulation of peripheral sympathetic nerves. Results identical to those obtained with lidocaine were observed with methyllidocaine, a quaternary derivative of lidocaine that does not easily penetrate the blood-brain barrier. These results suggest that the antiarrhythmic action of diphenylhydantoin against neurogenic arrhythmias is due to its central neurodepressant action. The results further suggest that, in contrast to diphenylhydantoin, lidocaine acts at peripheral neural or cardiac sites to antagonize neurogenic arrhythmias.