Alcohol abuse is a societal problem which exists with citizens from adolescence to the elderly. Chronic alcohol consumption has significant detrimental impact on the cardiovascular system, including the development of alcoholic heart muscle disease (AHMD). Subclinical depression of heart function observed with alcohol use is also associated with arrhythmogenesis, including ventricular tachycardia which may degenerate to fibrillation and sudden death. Circulating levels of the beta-adrenergic neurotransmitter, norepinephrine, are elevated with acute and chronic alcoholism. Beta- adrenergic overdrive is cardiotoxic, by inducing Ca2+ overload, and arrhythmogenic, by eliciting triggered automaticity. Adenosine normally released from the heart is an agent which attenuates the functional expression of beta-adrenoceptor activation (antiadrenergic action). Preliminary evidence presented herein indicates that the antiadrenergic action of adenosine is enhanced in the alcohol-treated heart. It is HYPOTHESIZED that the enhanced antiadrenergic action of adenosine provides protection for the heart against the action of high levels of norepinephrine observed in chronic alcoholism, thereby attenuating Ca2+ overload and arrhythmogenesis. The GOAL of this project is to study the mechanism(s) by which ethanol enhances the antiadrenergic action of adenosine. The experiments utilize techniques for assessing contractile function and receptor transduction at the organ and membrane levels.
The Specific Aims are to determine, with the isolated perfused heart and cardiomyocyte preparations, the effects of chronic ethanol treatment on the antiadrenergic action of adenosine with respect to contractile function (LVP, left ventricular pressure; +dPt max, the rate of pressure development; -dP/dT max, the rate of relaxation) and G protein expression. Results obtained from the proposed experiments will enhance our understanding of processes which, in the future, may be utilized to reduce injury in the alcoholic myocardium.
| Fenton , R A; Chung, E S (2001) Chronic ethanol enhances adenosine antiadrenergic actions in the isolated rat heart. Alcohol Clin Exp Res 25:968-75 |
