Mitochondrial function and excitation-contraction coupling in the development of alcoholic cardiomyopathy.
The effect of prolonged adminstration of ehtanol on cardiac metabolism, contractility, and ultrastructure was investigated. Dogs received 400 ml of a 25 percent solution of ethanol during a period of 3-6 months. Repeated heart muscle biopsied revealed a significant diminution in the activity of intramitochondrial NAD-linked isocitrate dehydrogenase in the animals exposed to alcohol. Oxidative, phosphorylation of mitochondria was measured polarographically using a vibrating oxygen electrode; respiratory control index and mitochondrial oxygen consumption were markedly reduced (p less than 0.001). Myocardial ATP content was significantly diminished (p less than 0.025). Electron microscopic changes observed consisted of mitochondrial degeneration, dehiscence of intercalated discs, and dilatation of intercellular spaces. The average force velocity curve was shifted downward and to the left in afterloaded contractions with a significant depression of Vmax (p less than 0.01). Both calcium binding and calcium uptake of mitochondria and sarcoplasmic reticulum were inhibited. These results suggest that a disorder in the generation of energy and a defect in calcium binding by subcellular membranes may be the determinant events leading to impaired myocardial function in the course of chronic alcoholism.
D000227:Adenine Nucleotides / Q000378:metabolism; D000437:Alcoholism / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000648:ultrastructure; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D007521:Isocitrate Dehydrogenase; D002118:Calcium