INFLUENCE OF TRIMETAZIDINE METABOLIC THERAPY ON CONNECTIVE TISSUE METABOLISM IN EXPERIMENTAL DIFFUSE ISCHEMIC NECROTIC CARDIOSCLEROSIS IN RATS WITH DIFFERENT RATES OF HYPOXIA RESISTANCE
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.
Lopez AD, Mathers CD. Measuring the global burden of disease and epidemiological transitions: 2002–2030. Ann Trop Med Parasitol. 2006; 100(5–6): 481–499.
Salemi VM, Leite JJ, Picard MH et al. Echocardiographic predictors of functional capacity in endomyocardial fibrosis patients. Eur J Echocardiogr 2009; 10(3): 400–405.
Iglezias SD, Benvenuti LA, Calabrese F. et al. Endomyocardial fibrosis: pathological and molecular findings of surgically resected ventricular endomyocardium. Virchows Arch 2008; 453(3); 233–241.
Ito A, Yamagiwa H, Sasaki RJ. Effects of aging on hydroxyproline in human heart muscle. Am Geriatr Soc. 1980; 28(9): 398–404.
Hoerstrup SP, Zünd G, Ye Q, et al. Tissue engineering of a bioprosthetic heart valve: stimulation of extracellular matrix assessed byhydroxyproline assay. ASAIO J. 1999; 45(5): 397–402.
Saturska HS. Peculiarities of cardioprotective effect of trimetazidine at experimental cardiosclerosis in rats with different sensitivity to hypoxia. Vestnik of Vitebsk State Medical University 2015; 14(1): 34–40. (in Russian).
Sharaev PN. Method for determination of free and bound hydroxyproline in serum. Lab business 1981; 5: 283–285. (in Russian).
Merkulov GA. Course of histological techniques. – L . : Medicine, 1969; 422 p. (in Russian).
Orlov АI. Mathematics cases: probability and statistics – the basic facts: a tutorial. M. : M-Press, 2004; 100 p. (in Russian).
Detry JM, Sellier P, Pennaforte S, et al. Trimetazidine: a new concept in the treatment of angina: comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. Br J Clin Pharmacol 1994; 37: 279–288.
Gupta R, Sawhney JP, Narain VS. Treatment of stable angina pectoris with trimetazidine modified release in Indian primary-care practice. Am J Cardiovasc Drugs. 2005; 5(5): 325–329.
Marzilli M, Klein WW. Efficacy and tolerability of trimetazidine in stable angina: a metaanalysis of randomized, double-blind, controlled trials. Coron Artery Dis 2003; 14: 171–179.
Sellier P, Broustet JP. Assessment of antiischemic and antianginal effect at trough plasma concentration and safety of trimetazidine MR 35mg in patients with stable angina pectoris: a multicenter, double-blind, placebo-controlled study. Am J Cardiovasc Drugs 2003; 3: 361–369.
Szwed H, Sadowski Z, Pachocki R, et al. Antiischaemic efficacy and tolerability of trimetazidine in elderly patients with angina. Clin Drug Invest 2000; 19: 1–8.
Szwed H, Sadowski Z, Pachocki R, et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J 2001; 22: 2267–2274.
Szwed H, Sadowski Z, Pachocki R, et al. The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients: a substudy from TRIMPOL 1. Cardiovasc Drugs Ther 1999; 13: 217–222.
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