INFLUENCE OF TRIMETAZIDINE METABOLIC THERAPY ON CONNECTIVE TISSUE METABOLISM IN EXPERIMENTAL DIFFUSE ISCHEMIC NECROTIC CARDIOSCLEROSIS IN RATS WITH DIFFERENT RATES OF HYPOXIA RESISTANCE

Abstract

Background. The change in metabolism of the connective tissue elements of heart is the central chain in pathogenesis of diffuse ischemic necrotic cardiosclerosis (DINC), which occurs after repeated epinephrine injury of myocardial tissues. Objective. This study proves that trimetazidine (TM) metabolic therapy has a protective effect on the development of DINC in rats with different rates of hypoxia resistance. Methods. Male white rats were divided into three groups due to the different rates of hypoxia resistance by means of the method of hypobaric hypoxia: rats with low, middle and high rates of hypoxia resistance. Each group was divided into equal subgroups: a control group, a DINC group (injections of epinephrine hydrotartrate (0,5 mg/kg of body weight) and calcium gluconate (5 mg/kg of body weight) two times), a control group administrated with trimetazidine dihydrochloride (10 mg/kg of body weight), a DINC group treated with TM every day (10 mg/kg of body weight) for all period of observation. Concentration of protein-bound oxyproline in blood serum was evaluated on the 7th, 14th and 30th days after the pathology simulation. Histological examination of Masson trichrome staining of myocardium was performed on the 30th days after the pathology simulation. Results. DINC increased the concentration of protein-bound oxyproline in blood serum on the 7th, 14th and 30th days after the pathology simulation, and followed by metabolic imbalances in diffuse connective tissue elements, which are rich in collagens. DINC+TM increased the concentration of protein-bound oxyproline in blood serum less intensively. Conclusions. The intensity of metabolic imbalances in diffuse connective tissue elements is the highest in the low resistant animals to hypoxia. Those results are confirmed by histological examination of the myocardium of rats with different resistance to hypoxia. Fibrotic regions in myocardium are rich in collagens. It has been revealed that the most pronounced therapeutic effect of TM is observed in animals with low resistance to hypoxia, slight – in animals with medium resistance to hypoxia, and the lowest – in animals with high resistance to hypoxia.