Publications by authors named "Mkhitarian L"

Our research demonstrate that ageing leads to changes in activity of electron-transporting enzyme complexes in myocardial mitochondria of old rats and to increased sensitivity of mitochondrial permeability transition pore to inductors of its opening--Ca2+ and phenylarsine oxide. We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (alpha-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) we observed the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensivity of lipid and protein free-radical peroxidation in the heart and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening.

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The results of study of influence of C6-analog of alpha-tocopherol on the structural and functional state of cardiomyocytes plasma membranes (CPM) in vitro are given. Under condition of incubation of CPM of intact animals the level of phospholipids was decreased, the level of fatty acids was increased, intensity of processes of free-radical oxidation (FRO) was significantly increased and activity of Na+, K(+)-ATPase was decreased in control samples of CPM. The analog of vitamin E supplementation at a concentration of 10 mg/ml of the medium significantly prevented the development of these changes.

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The results of research conducted on the cardiomyocytes plasma membranes structural and functional state under the experimental stress and atherosclerosis are displayed in this article. These experimental pathology is determined to be accompanied by some stereotypic quantitative and qualitative modifications occurred in the lipid matrix of the cardiomyocytes plasma membranes--increase of cholesterol content, decrease of phospholipids, accumulation of lisophospholipids and fatty acid. There are demonstrated results that the experimental stress has an atherogenic effect on the plasma membranes of cells by imputting the cholesterol into the membrane even in the intact animals with normal lipid metabolism.

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Amino acid composition of proteins from antigen preparations of the human heart conduction system has been studied. Differences in amino acid composition and relative affinity of the structure of two groups were found: between the sinus and atrioventricular nodes, the His bundle and contractile myocardium.

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An indirect ELISA method has been used to study formation of autoantibodies (AA) to myocardial myofibrillar proteins in patients with different clinical IHD forms. Purified myosin (MS), actin (AC) and tropomyosin (TM) of the intact human myocardium acted as antigens. The highest level of AA to MS and AC was found in patients with AMI (acute myocardial infarct): it exceeded twice that of the norm and 1.

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A study of autoimmune processes in 286 patients with different clinical forms of ischemic heart disease revealed a high frequency of antibodies to "healthy myocardium" antigen in patients with non-stable stenocardia and acute myocardial infarction that may indicate acquirement of antigenic properties of the healthy myocardium. Patients with unstable stenocardia also show an increased antibody titer to vascular antigens that indicates the possible role of activation of autoimmune reactions in the mechanisms of destabilization of the clinical course of ischemic heart disease.

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The lipid structure and Ca2+ permeability of red blood cell, hepatocyte and cardiomyocyte membranes were determined while investigating the effect of hypoxia caused by iron deficiency anemia upon the structural and functional state of biological membranes. The lipid composition and barrier characteristics of membranes change under conditions of hypoxia caused by experimental iron deficiency anemia. Quantitative changes in the cell membrane lipids may be considered as an important molecular mechanism of Ca2+ transport disorder in membranes, increase of Ca2+ permeability producing its surplus in the cells and subsequent metabolic homeostatic disturbances.

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With the purpose of preventing the development of acute clinical ischemic lesions of the myocardium, and their further progression, regression of coronary atherosclerosis the authors followed up for more than one year 250 patients with unstable stenocardia and singled out two groups of these patients, each group having important differences as to coronary reserve, functional state of the myocardium, lipid spectrum, dynamics of vasoactive substances, immunological reactivity, thrombocytic activity. Early detection of groups with an unfavourable course of IHD in patients with unstable stenocardia will allow to optimize treatment and avoid development of acute coronary catastrophies.

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Experiments on isolated hearts from adult and old rats have proved an age-dependent decrease in the resistance of contractile function and cardiac rhythm to ischemia and reperfusion. The restriction of coronary flow by 70% produced significant changes in various links of the Ca2+ transport system (an increase in sarcolemmal permeability for Ca2+ and a decrease in Ca(2+)-accumulating capacity of sarcoplasmic reticulum included). These changes, more marked in old animals, seemed to play an important role in the mechanisms of disturbances in cardiac function following coronary insufficiency.

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In experiments on isolated rat heart, it has been shown that in old animals the sensitivity to restriction of the coronary perfusion increases whereas the resistance of the heart to this restriction decreases. It was established that incomplete reversible ischaemia causes significant changes in different steps of Ca2(+)-transporting system of the myocardium which are more evident in older animals and which presumably account for the increased sensitivity of cardiac muscle to ischaemia.

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Status of thromboplastin, antiheparin and antithrombin characteristics of the native and cryopreserved bone marrow was studied experimentally on 12 rabbits. It is found that both the native and cryopreserved bone marrow possesses a pronounced and dilution resistant thromboplastin activity, whereas antithrombin and heparin activities were statistically unauthentic. In that connection the bone marrow injected into blood circulation may have different effects depending on the initial state of the recipient blood coagulation.

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Experiments with different species of animals and different models (in situ heart, isolated perfused heart, isolated papillary muscle) revealed a reduction of functional capacity of ageing heart. A decrease of Ca2+ uptake by sarcoplasmic reticulum and mitochondria and diverse age-dependent shifts were found in sarcolemma. The data obtained suggest that the development of the cardiac contractile function disorders in ageing largely depends of the age-related changes in the Ca2+ transport system.

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Experiments with animals with various species-specific life span (rats, rabbits, cats, dogs) and different models (in situ heart, isolated perfused heart, isolated papillary muscle) have proved the reduction of functional capacity of the ageing heart. Diversely directional age-dependent shifts have been established involving myocardial Ca2+ transport system, i.e.

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Ion transport properties and some components of lipid structure in myocardial sarcolemma were studied under conditions of short-term acute ischemia simulated in rabbits by means of intravenous administration of vasopressin at a dose of 0.2 U/kg. The acute coronary insufficiency was accompanied by distinct alterations in the parameters specific for calcium metabolism and transport: activity of Na+, K+-ATPase and the rate of Na+Ca2+ turnover were decreased, while 45Ca-binding ability and content of Ca2+ were increased in the myocardial sarcolemma.

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Disturbances in properties of the sarcoplasmic reticulum (SR) Ca-pump are found under conditions of experimental coronary insufficiency and confirmed by a decrease in the Ca2+-ATPase activity and in ability to the 45Ca uptake by SR membranes. Simultaneously the Ca2+ uptake by mitochondria increases. It is established that a rise in the total Ca content in the myocardium tissue is accompanied by its redistribution between the subcellular membrane structures and its accumulation in mitochondria.

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The area of exercise-associated ischemia in coronary patients was shown to depend on both total heart arterial damage and functional status of the myocardium. Stress related electrocardiographic ST depression in a limited number of leads was associated with satisfactory myocardial function. Generalized exercise-induced ischemia developed where left-ventricular myocardial function was disturbed significantly.

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After local restriction by 70% and 90% of coronary circulation the properties of calcium pump were altered in myocardial sarcoplasmic reticulum (SR), since the activity of Ca2+-dependent ATPase and binding of 45Ca2+ by the SR membranes in the ischemic zone and out of it were decreased. Increase in the ischemic state made these alterations more distinct. Under conditions of the experiment content of ATP decreased and the metabolism of electrolytes was altered.

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