Keywords
Abstract
Recently, in connection with the spread of alcoholic cardiomyopathy among the employable population of industrialized countries, an urgent need is the search for new drugs with a strictly targeted effect, taking into account the complex mechanisms of the damaging effect of ethyl alcohol on the myocardium. In this regard, the combination of L-arginine with thiotriazolin (developed by NPO Farmatron), as well as Mildronate, Mexidol and Thiotriazolin are of interest. Alcoholic cardiomyopathy (AC) was caused by intragastric administration with a metal probe of a 20 % ethanol solution at a dose of 8 g/kg for 90 days. All animals with AC were divided into 5 groups of 10 animals each. The studied drugs were administered intraperitoneally for 30 days – the proposed drug (L-arginine 100 mg/ml + thiotriazolin 25 mg/ml (4:1) – 200 mg/kg (in terms of L-arginine); Mildronate (Grindeks, Latvia) – 250 mg/kg; Mexidol (NPK Farmasoft, Russia) – 200 mg/kg, Thiotriazolin (Galichfarm, Ukraine) – 50 mg/kg. The control and intact groups received physiological saline. At the end of the experiment, animals were removed from the experiment 2–4 min after injection of sodium etaminal (40 mg/kg) (until the straightening reflex is lost) in order to minimize neurometabolic disorders. Morphometric analysis of cardiomyocytes was performed on an Axioskop microscope (Ziess, Germany) using a COHU-4922 video camera (USA) and introduced into the VIDAS-386 digital image analysis system (Kontron Elektronic, Germany). The following indicators were determined: the area of the nuclei of cardiomyocytes (μm2); the concentration of RNA in the nuclei of cardiomyocytes in optical density units; the concentration of RNA in the cytoplasm of cardiomyocytes in optical density units; cardiomyocyte nucleus density as an indicator of the number of cell nuclei per 1 mm2 of myocardial tissue area; nuclear cytoplasmic coefficient as an indicator of the total area of cardiomyocyte nuclei per 1 mm2 of myocardial tissue. As a result of the studies, it was found that on the 30th day after finishing of 90-day alcoholization in animals alcoholic cardiomyopathy is formed. A significant decrease of the nuclear cytoplasmic coefficient by 26,2 % and nuclear density by 19,1 % was observed in animals of the control group compared with intact animals, which reflects the presence of pathological myocardial hypertrophy, apoptosis and death of cardiomyocytes. Also, in animals of this group, an increase in the area of the nuclei of cardiomyocytes by 10,5 % was observed with a parallel decrease in the concentration of RNA in the nuclei by 24,0 % and in the cytoplasm of cardiomyocytes by 26,6 %. It was experimentally proved that the strength of the cardioprotective effect (the effect on the area and density of the nuclei of cardiomyocytes; the concentration of RNA in the nuclei and cytoplasm of cardiomyocytes, the nuclear cytoplasmic coefficient) the combined medicine of L-arginine/thiotriazolin significantly exceeds the reference drugs Mildronate, Mexidol and Thiotriazolin.