Alcoholic cardiomyopathy a histochemical study

Ferrans, Víctor J.; Hibbs, Richard G.; Weilbaecher, Donald G.; Black, William C.; Walsh, John J.; Burch, George E.

doi:10.1016/0002-8703(65)90449-7

Cited by 97 publications

(14 citation statements)

References 34 publications

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“…1 and 2 averaged 2.9 +0.3 /Ag/min in the controls and 2.8 ±0. 24 ,gg/min in the alcoholics. The relation of the stroke output to LV end-diastolic pressure responses were compared in the Group I noncardiac alcoholics with a group of control subjects.…”

Section: Methodsmentioning

confidence: 92%

“…The mechanism by which ethanol produces its effects on the myocardium is at present speculative. Histologic study of the myocardium in patients with cardiomyopathy has not revealed consistent findings (24,28), although lipid accumulation appears to be an important histochemical finding when care is taken to prevent lipid extraction in tissue preparation. Since lipid accumulation in heart muscle is one of the consequences of acute alcohol ingestion during the production of transient myocardial injury in the experimental animal (20), a possible role of triglyceride accumulation through an alteration of membrane or myofibrillar function may be considered (29).…”

Section: Restyltsmentioning

confidence: 99%

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Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy

Regan¹,

Levinson²,

Oldewurtel³

et al. 1969

J. Clin. Invest.

225

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A B S T R A C T Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease.During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index.To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/ 100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis.Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet-produced, after 12 wk, a progressive increase of heart rate and size,

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Section: Methodsmentioning

confidence: 92%

Section: Restyltsmentioning

confidence: 99%

Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy

Regan¹,

Levinson²,

Oldewurtel³

et al. 1969

J. Clin. Invest.

225

View full text Add to dashboard Cite

show abstract

“…In 1917, it was shown that oxygen consumption is increased after even moderate ingestion of ethanol in some individuals (10). Over the past 20 yr, light and electron microscopic changes in mitochondrial structure and function have been documented in myocardium from animals (11,12) and human subjects (13,14) exposed to ethanol. After a lag period of ethanol exposure in vivo, mitochondria isolated from the heart exhibit impaired rates of oxygen consumption, diminished respiratory control, and reduced P/O ratios (15)(16)(17)(18).…”

Section: Methodsmentioning

confidence: 99%

“…Such changes could be due to alterations in mitochondrial function. Consumption of alcohol over several weeks leads to gross morphological changes in heart mitochondria in laboratory animals (11,12) and human subjects (13,14). Impairment of mitochondrial function has been noted as well and it includes diminished phosphate/oxygen ratios (P/O)' and respiratory control ratios (15)(16)(17)(18); these are changes that do not occur after exposure of mitochondria to ethanol in vitro.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol.

Lange¹,

Sobel²

1983

J. Clin. Invest.

230

106

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A B S T R A C T Mechanisms responsible for alcohol-induced heart muscle disease have been difficult to elucidate partly because of previously obscure, demonstrable cardiac metabolism of ethanol. Recently, fatty acid ethyl esters were identified in our laboratory and found to be myocardial metabolites of ethanol. In the present study, they have been shown to induce mitochondrial dysfunction. Incubation of isolated myocardial mitochondria with fatty acid ethyl esters led to a concentration-dependent reduction of the respiratory control ratio index of coupling of oxidative phosphorylation and decrement of maximal rate of oxygen consumption. Furthermore, fatty acid ethyl esters were demonstrated to bind to mitochondria in vitro, and, importantly, 72% of intracellularly synthesized ethyl esters were found to bind to mitochondria isolated from intact tissue incubated with ethanol. Protein binding of fatty acid ethyl esters was markedly less than that of fatty acids. Because uncoupling of mitochondrial oxidative phosphorylation correlated with the cleavage of fatty acid ethyl ester shown to be initially bound to mitochondria, with resultant generation of fatty acid, a potent uncoupler, in a locus in or near the mitochondrial membrane, fatty acid ethyl esters may contribute to a potentially toxic shuttle for fatty acid with transport from physiological intracellular binding sites to the mitochondrial membrane; direct effects of fatty acid ethyl esters may also be deleterious. Operation of this shuttle as a result of ethanol ingestion and subsequent accumulation of fatty acid ethyl esters may account for the impaired mitochondrial function and inefficient energy production associated with toxic effects of ethanol on the heart.

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“…After an average of 18 mo observation when evaluation of nutritional status included assay of plasma vitamins, the chronic ethanol and control animals were anesthetized to evaluate left ventricular performance and morphology. Since myocardial lipid alterations have been reported after chronic ethanol intake (5,6), the myocardial metabolism of [1-'4C]oleic acid has also been assessed.…”

Section: Introductionmentioning

confidence: 99%