Experimental models for studying the effects of ethanol on the myocardium.
The ability to induce alcoholic cardiomyopathy has been tested in a variety of animal species. Myocardial alterations consistent with subclinical heart disease have been produced in many of these studies through a direct effect of ethanol or its metabolites upon the heart or a neurohumoral mechanism. In the rat most studies have, however, failed to finding diminished contractility in the basal state. In long-term animals the acute left ventricular responses to isoproterenol and calcium as well as pacing were reduced. Long-term studies in mongrel dogs fed 36 per cent of calories as ethanol produced an early decrease in left ventricular diastolic compliance related to interstitial collagen accumulation. Diminished contractility developed by four years. In addition to the morphologic evidence of distorted sarcoplasmic reticulum, in vitro experiments suggest important acute effects. Each mole of ethanol is bound tightly to each mole of protein comprising the Ca-ATPase pump, which is inhibited. Impaired uptake and binding of calcium by the sarcoplasmic reticulum has been observed in chronic alcohol models at one to two day intervals following the last exposure to ethanol. In addition, the flux of calcium ion does not appear normal in terms of access to contractile protein, where the calcium regulated inhibition of the troponin interaction with myosin is impaired. Experimental studies in a canine model of alcoholism revealed that the ventricular fibrillation threshold was moderately reduced in the basal state after 18 months and was diminished further after acute exposure.
Regan
T J
TJ
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark.
Morvai
V
V
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism
D002118:Calcium