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We developed a translation model of alcoholic cardiomyopathy in rats. By the end of forced alcoholization (the rats received 10% ethanol solution as the only source of fluid for 24 weeks; mean daily ethanol consumption was 5.0-6.5 g/kg), the rats developed dilated heart failure. Echocardiography and morphometric study of the myocardium revealed a decrease in inotropic function of the heart and dilatation of the right and left ventricles. Fatty degeneration of the myocardium (pathognomonic sign of alcoholic cardiomyopathy) and decrease in electrical stability of cardiomyocytes reliably reproduce the clinical pattern of alcoholic cardiomyopathy.

Dynamic echocardiographic monitoring in rats subjected to forced alcoholization showed the formation of disorders in intracardiac hemodynamics characteristic of ethanol cardiomyopathy formed by the end of 24-week continuous ethanol consumption. The results of echocardiographic monitoring were confirmed by histological and morphometric studies demonstrating fatty infiltration of the myocardium pathognomonic for this condition and bifocal dilatation of cardiac ventricles. These results persuasively demonstrate that echocardiographic studies on small animals are valid and can be used for search for cardiotropic drugs and studies of the mechanisms of their activities.

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole. [ABSTRACT FROM AUTHOR]