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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]

Chronic alcohol abuse leads not only to a significant human psychic and social degradation, but also promotes the alcoholic cardiomyopathy formation, that is one of the leading causes of high mortality of alcoholics. However, to date in clinic there are no unified approaches in the prevention and treatment of alcoholic cardiomyopathy, first of all, due to the lack of the adequate model in the experimental pharmacology, which can assess the stages of formation of alcoholic cardiomyopathy objective and in real time, and thus create the basis for the search and study the mechanisms of action of drugs for the treatment of this serious disease. Studing the possibility of echocardiography using in experiments with rats exposed to prolonged forced alcoholism is one of the approaches to solve this problem. It was shown that the significant changes of intracardiac echocardiography hemodynamics corresponding to the known from the clinic, begining to form from the 20th week of systematic consumption of alcohol by rats. At this time interval the reduction in inotropic function of the heart in alcoholized rats compared to control is observed: fraction shortening (FS) is 41.9% (40.3-42.2) and 51.3% (48.8-59.1) respectively, and ejection fraction (EF) 78.8 (77.4-79.2) and 87.5% (84.6-92.4) respectively, p = 0.0215. The dilated heart failure develops in the rats from the 24 week of regular alcohol consumption, as evidenced not only by dynamic reducing of FS and FV, but also by the dilatation ofthe heart. For example, the end-systolic size of the left ventricle in animals consuming alcohol compared with control increased more than 2 times (4.31 mm (3.80-4.41) and 2.0 mm (1.85-2.36); p = 0.0008, and the end-diastolic dimension was 5.95 mm (5.13-6.37) and 4.52 mm (3.85-4.90) respectively; p = 0.0171. Thus, the echocardiographic picture characteristic for alcoholic dilated cardiomyopathy is formed by the end of the 24th week of chronic alcoholiation.

Features of early postischemic cardiac remodeling is well studied both in the clinic and in the experiment. However, the data for this process in the first 60 minutes after occlusion of the coronary vessel in the literature are absent practically. In experiments in rats in which acute myocardial ischemia was reproduced by the simultaneous ligation of the left coronary artery, with the help of echocardiography it is shown that in the first minutes of ischemia in left ventricular systolic function of the heart sharp drops: so, at the 20th minute of ejection fraction (EF) is reduced up 84.5 (79.3-89.2) to 51.7 (50.2-54.4)% - P < 0.05; fraction shortening (FS) is decreased up 52.6 (47.8-59 and 3) to 26.5 (25.9-28.1)% - P < 0.05; a end-systolic dimension (ESD) of the left ventricle is increased up 1.90 (1.70-2.26) to 3.80 (3.50-4.10) mm - P < 0.05, whereas the sham animals were not observed any statistically significant violations of left ventricular systolic function during the observation period (60 minutes). In the period up 20 to 60 min of ischemia is noted a gradual improvement of the relative systolic heart function. At the 60th minute of ischemia all recorded echocardiographic parameters were significantly (P < 0.05) different from those reported in the period from 10 to 20 min of ischemia - EF 62.4 (59.0-64.3)%, FS 33, 7 (31.1-35.2)%, ESD 3.10 (2.80-3.40) mm, etc. Analysis of the results suggests that noted in our experiments the maximum reduction in left ventricular ejection time coincides with the peak of arrhythmogenesis, i.e. with a maximum risk of sudden cardiac death.