Antiarrhythmic effects of diazepam during coronary artery occlusion in dogs

The ventral interventricular branch of the left coronary artery was ligated in a 2-step operation in 10 dogs whose electrocardiograms and systemic arterial blood pressures were then monitored during the next 7 days. Monitoring was done in awake dogs given 1 mg of diazepam per kilogram of body weight (intravenously administered in 3 dogs and orally in 7). Because ventricualr ectopic activity was greatest during the interval of 10 to 48 hours after ligation, the antiarrhythmic activity of diazepam was recorded during this 38-hour interval. After administration of diazepam by either route, frequency of ventricular ectopic beats decreased from 98 to 80%. THIS REDUCTION BETAN IMMEDIATELY AFTER THE INTRAVENOUS ADMINISTRATION AND PERSISTED FOR ONLY 5 MINUTES; REDUCTION BEGAN APPROXIMATELY 1 HOUR AFTER THE ORAL ADMINISTRATION AND PERSISTED 4 TO 6 HOURS. Systemic arterial blood pressure decreased only after the intravenous administration. It is concluded that diazepam is effective in reducing the frequency of ventricular ectopic activity after occlusion of major branches of coronary arteries, that diazepam works independent of alterations in systemic arterial blood pressure, and that orally administered diazepam prolongs antiarrhythmic activity. Possibly, the adjuvants present in the parenteral form of diazepam reduce antiarrhythmic activity by being, themselves, arrhythmogenic.