Mechanism of myocardial contractile depression by clinical concentrations of ethanol. A study in ferret papillary muscles.

Abstract

Moderate alcohol intoxication in man, a ubiqitious social event, causes acute but reversible myocardial depression, the mechanism of which is unknown. We investigated whether this depression could be due to a direct effect of ethanol on the process of electromechanical coupling by simultaneously measuring the transmembrane action potential and contraction, or the cytosolic calcium transient (via aequorin photoluminescence) and contraction in isolated ferret right ventricular papillary muscle. Ethanol, in concentrations that are similar to plasma levels in man during intoxication (0.15 vol %), de-pressed the force of contraction -10%. The step in the electromechanical process that was affected appeared to be the calcium-myofilament interaction, as there was no change in the transmembrane action potential or cytosolic calcium transient. This inhibition was quickly reversed by removal of the ethanol from the perfusate.On the other hand, higher concentrations of ethanol produced changes in contraction, the calcium transient, and the action potential, suggesting multiple levels of inhibition of electromechanical coupling. Increasing the perfusate calcium or use of the calcium channel agonist, BAY-K 8644, increased cytosolic calcium to near maximum but had little effect on contractility, confirming that the relationship between calcium and the myofilaments had been altered.These data suggest that the acute depression in ventricular function seen with alcohol consumption may be due to a direct effect on electromechanical coupling through inhibition of the calcium myofilament interaction. (J. Clin. Invest. 1990.

Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes

“…The hallmarks of alcoholic cardiomyopathy are altered cardiac contractile function and impaired intracellular Ca 2ϩ mobilization such as decreased SR Ca 2ϩ function, which may underlie the altered cardiac mechanics (2,3,8,24,29,30). It is postulated that inhibition by ethanol of Ca 2ϩ regulatory proteins such as Ca 2ϩ pumps and channels may play a role in the decreased cytosolic Ca 2ϩ concentration.…”

Basal and Ethanol-Induced Cardiac Contractile Response in Lean and Obese Zucker Rat Hearts

“…Chronic alcohol (ethanol) ingestion leads to impaired cardiac function, including depressed cardiac contraction, ventricular hypertrophy and electrophysiologic abnormalities [3,5,9,16]. Moreover, excessive ethanol may be associated with alcoholic cardiomyopathy, a clinical condition that leads to ventricular dysfunction, hypertension and heart failure [2,29].…”

“…Although ethanol has been reported to both improve and impair cardiac function in human and experimental animals, it depresses contractile function unequivocally in isolated cardiac preparations [1,[3][4][5]8]. Recent studies suggested that changes at the single cardiac myocyte level, such as myofibril Ca 2+ sensitivity, plasma membrane properties and intracellular Ca 2+ , are responsible for ethanol-induced myocardial alteration [5,9,18,25].…”

Drug-Induced Cardiomyopathies

“…These studies have demonstrated that ethanol has multiple effects on the myocardium, and as such could depress the force of contraction at several points in the process of electromechanical coupling, probably at the level of the myofilaments. The effect was found to be reversible by increasing the amount of calcium presented to the myofilaments or by washing out the ethanol (Guarnieri and Lakatta 1990). This cardiodepresive action of ethanol is evidenced in experimental models designed with autonomic blockade, heart denervation, or isolated cells.…”

“…it has a direct negative inotropic action with a reversible dose-dependent decrease in myocardial contractility. Most studies of isolated myocardium have sought to explain these acute and reversible changes in the force of contraction by using pharmacologic concentrations of ethanol in the 1% (by volume) range (Knochel 1983;Guarnieri and Lakatta 1990). These studies have demonstrated that ethanol has multiple effects on the myocardium, and as such could depress the force of contraction at several points in the process of electromechanical coupling, probably at the level of the myofilaments.…”