Abrupt Termination of an Ethanol Regimen Provokes Ventricular Arrhythmia and Enhances Susceptibility to the Arrhythmogenic Effects of Epinephrine in Rats

Background: Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. Methods: Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. Results: Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. Conclusions: Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen.