TRANSLATION MODEL OF ALCOHOLIC CARDIOMYOPATHY

DOI: https://doi.org/None

S.A. Kryzhanovskii, I.B. Tsorin, L.G. Kolik, V.N. Stolyaruk, M.B. Vititnova, E.O. Ionova, A.V. Sorokina, A.D. Durnev, S.B. Seredenin Research Zakusov Institute of Pharmacology, Baltiyskaya st., 8, Moscow, 125315, Russian Federation

The aim of the study – the development of translational models of the alcoholic cardiomyopathy in rats to search and study the action mechanism of new original drugs for the treatment of this pathology. Methods. The complex of echocardiographic, electrophysiological, morphological and biochemical studies was used, which allowed to evaluate and differentiate the stages of formation and intensity of alcoholic cardiomyopathy. Results. Dynamic echocardiographic study showed that alcoholic cardiomyopathy simptoms (reduced inotropic function of the heart) appeared with the end of the 20th week of continuous forced alcoholisation of animals with 10% ethanol, and dilated alcoholic cardiomyopathy was formed to the end of the 24th week of alcoholisation. The results of echocardiography was confirmed by morphometric studies of myocardium, which revealed dilatation of the right and left heart ventricles to the end of 24 week of ethanol consumption. Thus, if an area cavity of the left and right ventricles in intact rats were on an average, 4,23±0,44 and 2,95±0,18 mm2 respectively, in the animals with established alcoholic cardiomyopathy, these values were 12,55±0,18 mm2 (p≈0,008) and 4,87±0,62 mm2 (p≈0,033), respectively. In the same time histological studies indicated the fatty infiltration presence that was pathognomonic for alcoholic cardiomyopathy. Electrophysiological studies have shown that in rats with established alcoholic cardiomyopathy the threshold of electrical fibrillation of the heart is almost 2 fold (p≈0,009) lowered, that indicated the progression of myocardium electrical instability. These observations have a good correlation with clinical data that demonstrate the high risk of sudden death in patients suffering from alcoholic cardiomyopathy. Conclusion. A new translation model of alcoholic cardiomyopathy in rats was offered. It is shown that by the end of the 24th week of continuous alcoholisation (daily average consumption of ethanol 5,0–6,5 g/kg) in rats the dilated heart failure cardiomyoliposis and reduced electrical stability of cardiomyocytes develops, that well confirmed by clinical picture of alcoholic cardiomyopathy.
Keywords: 
translation model, rats, alcoholic cardiomyopathy, echocardiography, morphology, electrophysiology, sudden death

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