Enhancement of Epinephrine Induced Cardiac Arrhythmias by Tetraethylammonium Chloride (Etamon). ∗

Abstract

In the experiments to be reported herein tetraethylammonium chloride has been shown to intensify the cardiac arrhythmias occurring in dogs during cyclopropane anesthesia. Secondly, experiments on unanesthetized animals suggest that the choice of a pressor agent for use as an antidote after tetraethylammonium chloride may be critical. After tetraethylammonium injection epinephrine resulted in ventricular tachycardia whereas phenylephrine (Neo-Synephrine) caused no arrhythmias.

Cardiac arrhythmias occurring during cyclopropane anesthesia have been demonstrated experimentally to depend upon reflex sensitization of the heart to epinephrine. 1 Cyclopropane stimulates receptors located in the abdominal viscera, producing afferent impulses which pass to the cord by way of fibers travelling with the splanchnics. The reflex center is located in the brain, presumably in the hypothalamus. Efferent impulses pass to the heart by way of cardiac sympathetics. Since interruption of this pathway at any point has prevented the arrhythmias, the tetraethylammonium ion should theoretically block the reflex sensitization. This agent has been reported to interrupt sympathetic impulses by ganglionic blockade 2 and consequently was expected to block the efferent impulses.

When it was found that tetraethylammonium potentiated the cardiac effects of epinephrine under cyclopropane, the cardiac effects of the ion and epinephrine were also investigated in unanesthetized animals. Epinephrine has been recommended as an antidote for the profound hypotension which may follow the clinical administration of tetraethylammonium. 3

Cyclopropane-epinephrine Ventricular tachycardia was produced in the dog by the method described by Meek et al. 4 The only modification of this technic was reduction of the standard test dose of epinephrine in order to lower the mortality from ventricular fibrillation. After the control duration of ventricular tachycardia had been determined, tetraethylammonium chloride§ was administered intravenously over a period of 60 seconds in doses of 5 to 20 mg/kg.