Metabolic Effects of Ethanol on the Rabbit Heart

A B S T R A C T Splanchnic metabolism was studied to quantify changes underlying the fatty liver, hyperlipemia, and hypoglycemia produced by ethanol. Four subjects fasted for 15 h were compared with five subjects fasted for 69 h under basal conditions and during continuous intravenous infusion of sufficient ethanol to give a concentration of 3-5 mM in arterial blood plasma. Splanchnic storage of fatty acids was estimated from the difference between uptake of FFA and secretion of derived products. Basal values for splanchnic uptake of FFA were twofold higher after the 69-h fast while splanchnic storage of fatty acids and production of ketone bodies increased threefold. Values for basal secretion into the blood of triglycerides derived from FFA were similar in the two groups. In both nutritional states, the fraction of FFA taken up in the splanchnic region oxidized to ketone bodies and to C02 fell when ethanol was given because of preferential oxidation of ethanol to acetate, and the fraction esterified rose. However, systemic transport and splanchnic uptake of FFA fell with ethanol in subjects fasted 15 h, so that neither storage of triglycerides in splanchnic tissues nor secretion into the blood Portions of this work were presented at the Alfred

Section: Discussionsupporting

confidence: 63%

Effects of a 3-day fast and of ethanol on splanchnic metabolism of FFA, amino acids, and carbohydrates in healthy young men.

Wolfe¹,

Havel²,

Eb³

et al. 1976

“…Despite its prevalence, its well-characterized ethanol-induced depression of myocardial contractility (2-4) and arrhythmias (5), and changes that it produces in myocardial lipid composition (6)(7)(8), the pathophysiology of this disorder has remained obscure. The apparent lack of demonstrable cardiac metabolism of ethanol (6,9) has made it difficult to elucidate a direct link between exposure to alcohol and the metabolic changes noted.…”

Section: Introductionmentioning

confidence: 99%

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

Lange¹,

Sobel²

1983

229

106

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.

“…Dogs exposed to a prolonged period of alcohol intake show a marked increase in triglycerides (1,9,10) and a diminution in free fatty acid content of heart muscle. Ethanol also increases plasma free fatty acids, triglycerides, and cholesterol.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Prolonged Administration of Ethanol on Cardiac Metabolism and Performance in the Dog

Pachinger¹,

Tillmanns²,

Mao³

et al. 1973

A B S T R A C T The effect of prolonged administration of alcohol on mitochondrial function and high-energy phosphate (ATP) of heart muscle was investigated in dogs. Animals were divided into two groups, a control group and a group that received alcohol. In the experimental series, dogs received 400 ml of a 25% solution of alcohol added to the food and drinking water. Measurements were carried out after ethanol had been withheld for 2 days. Total myocardial blood flow, cardiac output, and myocardial 02 consumption remained at control levels. Measurement of cardiac contractility using the maximal rate of left ventricular pressure rise (dP/dtmax) showed no change in animals exposed to alcohol. When the afterload of the heart was increased with angiotensin, a slight but not significant decline in cardiac contractility was observed. Activities of various intramitochondrial and extramitochondrial enzymes were measured in both groups. After alcohol administration, the primarily intramitochondrial isocitrate dehydrogenase diminished. ATP in heart muscle of dogs exposed to alcohol declined, and mitochondrial oxygen consumption and respiratory control indices diminished. These observations suggest that the primary lesion leading to alteration of myocardial performance is a biochemical malfunction of the mitochondria, which at this early stage is not reflected in changes in myocardial contractility.