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.

The effect of prolonged administration of alcohol on calcium binding and uptake by sarcoplasmic reticulum and mitochondria and on respiratory function of mitochondria was investigated in heart muscle of dogs. Dogs were paired and maintained with and without alcohol for 6 months; alcohol was administered by adding it to drinking water and food with vitamin supplements. Measurements were made after alcohol had been temporarily withheld for 2 days. Prolonged alcohol ingestion resulted in a decline in calcium binding and uptake by sarcoplasmic reticulum and mitochondria, suggesting a diminished affinity of the reticular and mitochondrial membranes for calcium ions. The endogenous calcium content of mitochondria and sarcoplasmic reticulum decreased. Prolonged alcohol administration failed to alter cardiac contractility, although contraction and relaxation tended to diminish following the administration of angiotensin. The results illustrate that one link in the regulation of the state of contraction or relaxation involving myofibrillar calcium transport is weakened in dogs maintained on alcohol for prolonged periods of time. KEY WORDScalcium binding and uptake mitochondrial respiration sarcoplasmic reticulum alcohol and cardiac contractility excitation-contraction coupling

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