Nizhenkovskaya I. Biochemical and membrane mechanisms of myocardial injury under experimental cardiac insufficiency and its correction by physiologically active substances of metabolic nature.

It was shown that under rubomycin intoxication the severe biochemical, ultrastructural and functional alterations inside cardiomyocytes develop that are manifested by the mitochondrial oxidative reactions damage, nicotinamide coenzymes NAD+ and NADP+ as well as principal cardiac metabolic energy resources glycogen, creatine phosphate, ATP content and creatine kinase activity decrease. The rubomycin induced cardiac cells lesion also results in the oxidative stress development displayed by significant rise of lipoperoxidative processes that leads to the profound changes in polyunsaturated fatty acids composition, especially in arachidonic acid content, and glutathione antioxidant system functional activity decrease. Introduction to the cardiac insufficiency rats of metabolic nature cardiotonics Sufan, succinate and tryptophan derivative, and crown-ether Сarbicyl, which is uracyl derivative, results in considerable amelioration of rubomycin induced cardiomyocytes metabolic and ultrastructural lesion. Under Suphan and Carbicyl treatment, essential correction of cellular bioenergetics, peroxidative reactions in membrane lipid matrix and glutathione antioxidant system activity takes place. To elucidate the molecular mechanisms of Sufan and Carbicyl cardiac membranes protective efficiency, the physicochemical interactions between cardiotonic compounds and model phospholipid membranes were studied. The surface activity of L-, D- and D,L-Sufan was investigated, and the ability of Sufan isomers to monolayers formation was shown. The energy parameters of intermolecular complexes between Suphan, crown-ether derivatives and biomolecules, namely L-aminoacids and membrane phospholipids, were calculated. Interactions between myocardial sarcolemma membrane lipids and proteins and metabolic cardiotonics are thought to be of primary importance for the cardiotonic pharmacological activities of the latter.