[To the potential use of alcoholic cardiomyopathy echocardiography assessment of forming].

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.

[Peculiarities of myocardial remodeling in the acutest phase of experimental myocardial infarction in rats].

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.

[Effects of afobasol in the reperfusion arrhythmia model].

Afobasol caused insignificant dose-related decrease of main parameters of cardiac activity in narcotized animals and was similar to pulse-decelerating calcium antagonists in terms of hemodynamic effects. Reperfusion after acute regional myocardial ischemia induced malignant cardiac rhythm disorders and progressive impairment of cardiac pump function. These changes combined with increased peripheral resistance created conditions for the development of cardiac insufficiency. Afobasol administered 5 min before the onset of reperfusion significantly reduced the frequency and intensity of cardiac rhythm disturbances and thereby prevented cardiac insufficiency. It is conjectured that cardioprotectice action of afobasol in these conditions was due to its ability to activate sigma-1 receptors in cardiomyocytes and thereby protected heart cells from excessive accumulation of Ca2+ ions.

[Afobasol antifibrillation activity in animals with the intact and denervated myocardium].

The influence of afobasol on threshold electrical fibrillation of the heart was studied in experiments on narcotized cats. It significantly elevated the cardiac fibrillation threshold in animals with intact myocardium and resembled class 1B anti-arrhythmic drug lidocaine in terms of this activity. Similar results were obtained using cats with denervated myocardium. These observations indicate that in the model of electrical fibrillation of the heart afobasol has marked antifibrillation action mediated through cardiomyocytes. This inference was confirmed by the studies of afobasol effects on cardiac rhythm variability in rats with acute myocardial ischemia. It is supposed that afobasol prevents cardiac fibrillation acting as an agonist of cytosolic sigma-1 receptors in cardiomyocytes

[Afobasol efficacy in a model of vagotonic atrial fibrillation].

The new anxiolytic agent afobasol (Russia) was introduced into clinical practice by V. V. Zakusov Research Institute of Pharmacology. When administered to cats with vagotonic atrial fibrillation afobasol (7.5 mg/kg v/v) exhibited anti-arrhythmic activity at least as high as that of class 1 and III anti-arrhythmic agents (etacisin and cardiocyclide respectively) (Vaughan Williams classification). However, duration of its action was much smaller. These experimental findings were confirmed in clinical studies involving patients with severe psychosomatic pathology associated with paroxysmal flutter. It is supposed that afobasol activates cytosolic sigma-1 receptors in cardiomyocytes and may be used to manage psychoasthenic conditions accompanied by cardioneuroses and/or cardiophobias with disturbed rhythmic activity of the heart.