Arrhythmias in the Alcoholic

Guideri, Giancarlo

Abstract

It has been reported that chronic alcohol users are susceptible to severe ventricular dysrhythmias both during phases of alcohol consumption and withdrawal, and that alcoholics appear more prone to encounter sudden death. No experimental animal model of this phenomenon is available. Elevation of mineralocorticoids and catecholamines and diminution of vasopressin and magnesium levels are among the derangements produced by heavy alcohol consumption. In the rat, these same conditions, namely, treatment with desoxycorticosterone acetate (DOCA), a potent mineralocorticoid, or imposition of dietary magnesium deficiency as well as lack of vasopressin (Brattleboro rat), render the animal highly vulnerable to catecholamine-induced ventricular dysrhythmias and sudden death in ventricular fibrillation (VF). Thus, in DOCA pretreated rats the LD50 of isoproterenol, a potent sysnthetic cathecholamine, is decreased by a factor of 40,000 -90,000 to 14.5 Mug/kg as compared to the LD50 of 600-1,300 mg/kg in untreated controls. Death in the DOCA pretreated rat is invariably due to VF. Aminophylline further diminishes the LD50 to 3.0 Mug/kg and permits VF by endogenous catecholamines released during stress of handling. A similar high incidences of VF is obtained in magnesium deficient and Brattleboro rats. It is proposed to evaluate the rat as a model to study severe dysrhythmias associated with high alcohol consumption. Experiments will be conducted in rats. Susceptibility to dysrhythmias to isoproterenol and epinephrine will be assessed by monitoring the ECG in unanesthetized, unrestrained rats during alcohol consumption and during withdrawal. Blood ethanol concentration as well as serum and myocardial levels of sodium, potassium, magnesium and calcium will be determined and their relationship to dysrhythmias will be assessed. If the rat model is successful, this preliminary work could lead to studies of the mechanism by which vulnerability of the heart to severe rhythm disorders is increased by alcohol as well as to studies involving potential therapeutic agents.