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(Circulation. 1973;47:974.)
© 1973 American Heart Association, Inc.

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Deleterious Effects of Bretylium in Cats with Digitalis-Induced Ventricular Tachycardia

RICHARD A. GILLIS PH.D.¹; MARGARET M. CLANCY B.S.¹; REBECCA J. ANDERSON B.A.¹

¹ From the Department of Pharmacology, Georgetown University Schools of Medicine and Dentistry, Washington, D. C.

The effect of bretylium on ventricular tachycardia induced by digitalis was studied in Dialurethane-anesthetized cats with continuous monitoring of the electrocardiogram and arterial blood pressure. Ventricular tachycardia was produced by repeated injections of deslanoside (25 µg/kg) at 15 min intervals. Only one of eight animals showed conversion of ventricular tachycardia to sinus rhythm with bretylium administration (2-100 mg/kg i.v.). In each animal, bretylium increased the ventricular rate. The effect of bretylium (30 mg/kg i.v.) on duration of ventricular tachycardia induced by deslanoside (0.75 µg/kg/min) was also studied. Duration was shortened from 65 ± 8.0 min to 7 ± 1.0 min, but the reduction was due to the intervention of either ventricular fibrillation or severe hypotension caused by bretylium. Pretreatment with propranolol (0.5 mg/kg i.v.) prevented these deleterious effects and unmasked an antiarrhythmic effect of bretylium since duration of ventricular tachycardia was significantly shorter (40 ± 6.0 min) than the controls (65 ± 8.0 min). In addition, an antiarrhythmic effect of bretylium was noted when it was administered as a dose of 30 mg/kg ip to animals 24 and 4 hours prior to deslanoside intoxication; 231 µg/kg deslanoside were now required for inducing ventricular tachycardia as compared to 175 µg/kg deslanoside in controls. Thus, bretylium given alone during a digitalis-induced ventricular tachycardia increases both the rate of ventricular tachycardia and the likelihood of ventricular fibrillation. These deterious effects appear to be related to a norepinephrine-releasing action and may be avoided by either pretreatment with propranolol or administration of bretylium several hours prior to digitalis intoxication.

Key Words: Antiarrhythmic action • Norepinephrine • Arrhythmogenic action • Ventricular fibrillation • Neurodepression • Deslanoside • Propranolol

Submitted on June 29, 1972
Accepted on December 13, 1972