RESUMO
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. This complex may be used to treat mitochondrial dysfunction under numerous pathologies of cardiovascular system, as well as in ageing.
Assuntos
Envelhecimento/metabolismo , Antioxidantes/farmacologia , Metionina/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Parabenos/farmacologia , Ubiquinona/biossíntese , alfa-Tocoferol/farmacologia , Animais , Metabolismo Energético , Radicais Livres/metabolismo , Peroxidação de Lipídeos , Masculino , Mitocôndrias Cardíacas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/biossíntese , Poro de Transição de Permeabilidade Mitocondrial , Dilatação Mitocondrial/efeitos dos fármacos , Oxirredução , RatosRESUMO
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. All of these can be evidence of effective membranes protective action of C6-analog of vitamin E on CPM.
Assuntos
Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Miocárdio/citologia , Vitamina E/análogos & derivados , Vitamina E/farmacologia , Animais , Membrana Celular/enzimologia , Células Cultivadas , Ácidos Graxos/metabolismo , Radicais Livres , Fosfolipídeos/metabolismo , Coelhos , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-AtividadeRESUMO
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. All these modifications are also accompanied by the activation of free-radical oxidation. All these changes are capable to lie in the basis of physical and chemical properties mechanism modification of membranes: modification of lipid matrix, change of viscosity, ion-transport properties of cardiomyocytes membranes, oppression of Na+, K(+)-ATPase activity.
Assuntos
Miocárdio/citologia , Animais , Membrana Celular/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Radicais Livres , Peroxidação de Lipídeos , Lipídeos de Membrana/metabolismo , Miocárdio/metabolismo , Fosfolipídeos/metabolismo , Coelhos , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Aminoácidos/análise , Antígenos/análise , Sistema de Condução Cardíaco/imunologia , Antígenos/isolamento & purificação , Autoanálise/estatística & dados numéricos , Sistema de Condução Cardíaco/química , Humanos , Peptídeos/análise , Proteínas/análiseRESUMO
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 1.5 times that in patients with IAP (instable angina pectoris). Moreover the AA level in IAP patients exceeded that of normal 1.5 times. In PC (postinfactional cardiosclerosis) patients the MS AA and AC AA tend to the norm. The TM AA contents in PC patients is 1.2 times higher than that in AMI and IAP patients, not differing from the norm in all patient groups. The role of autosensibilization to contrectile proteins in progress of IHD and development of AMI is discussed.
Assuntos
Actinas/metabolismo , Angina Pectoris/metabolismo , Arteriosclerose/metabolismo , Autoanticorpos/metabolismo , Infarto do Miocárdio/metabolismo , Miofibrilas/metabolismo , Miosinas/metabolismo , Tropomiosina/metabolismo , Ensaio de Imunoadsorção Enzimática , HumanosRESUMO
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.
Assuntos
Doenças Autoimunes/imunologia , Isquemia Miocárdica/imunologia , Adulto , Angina Pectoris/imunologia , Angina Instável/imunologia , Aorta/imunologia , Arteriosclerose/imunologia , Autoanticorpos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/imunologia , Miocárdio/imunologia , Esforço FísicoRESUMO
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.
Assuntos
Anemia Hipocrômica/fisiopatologia , Membrana Eritrocítica/fisiologia , Coração/fisiopatologia , Hipóxia/fisiopatologia , Fígado/fisiopatologia , Anemia Hipocrômica/sangue , Anemia Hipocrômica/complicações , Animais , Cálcio/fisiologia , Membrana Celular/fisiologia , Permeabilidade da Membrana Celular/fisiologia , Fenômenos Químicos , Físico-Química , Hipóxia/sangue , Hipóxia/etiologia , Ferro/sangue , Lipídeos de Membrana/análise , RatosRESUMO
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.
Assuntos
Angina Instável/diagnóstico , Adulto , Idoso , Angina Instável/epidemiologia , Angina Instável/reabilitação , Biomarcadores , Quimioterapia Combinada , Seguimentos , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoAssuntos
Doenças Cardiovasculares/radioterapia , Micro-Ondas/uso terapêutico , Adulto , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/radioterapia , Doenças Cardiovasculares/fisiopatologia , Doença das Coronárias/fisiopatologia , Doença das Coronárias/radioterapia , Estudos de Avaliação como Assunto , Hemodinâmica/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física/efeitos da radiaçãoRESUMO
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.
Assuntos
Envelhecimento/fisiologia , Cálcio/metabolismo , Doença das Coronárias/fisiopatologia , Coração/fisiopatologia , Reperfusão Miocárdica , Miocárdio/metabolismo , Animais , Transporte Biológico , Circulação Coronária , Creatina Quinase/metabolismo , Feminino , Frequência Cardíaca , Técnicas In Vitro , Contração Miocárdica , Ratos , Ratos EndogâmicosRESUMO
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.
Assuntos
Envelhecimento/fisiologia , Cálcio/metabolismo , Circulação Coronária/fisiologia , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Animais , Transporte Biológico/fisiologia , Técnicas In Vitro , Perfusão/instrumentação , Perfusão/métodos , Ratos , Ratos EndogâmicosRESUMO
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. The fact should be taken into account in clinics.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Preservação de Sangue/métodos , Medula Óssea , Criopreservação/métodos , Tromboplastina/farmacologia , Extratos de Tecidos/farmacologia , Animais , Coagulação Sanguínea/fisiologia , Técnicas In Vitro , CoelhosRESUMO
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.
Assuntos
Envelhecimento/fisiologia , Cálcio/metabolismo , Contração Miocárdica , Miocárdio/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Transporte Biológico , Gatos , Cães , Estimulação Elétrica , Hemodinâmica , Técnicas In Vitro , Músculos Papilares/fisiologia , Coelhos , Ratos , Sódio/metabolismoRESUMO
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. an increase in the rate of Na+-Ca2+ exchange and passive Ca2+ transport across sarcolemma and a decrease in its Ca2+-binding capacity and a decrease in Ca2+ accumulation by sarcoplasmic reticulum and mitochondria (Ca2+ uptake). The experiments revealed a decrease in the Ca2+ ATPase myosin activity in the myocardium of aged animals and absence of age changes in the K+ ATPase activity. The findings obtained suggest that the development in the cardiac contractile function disorders in ageing largely depends on the age-related changes in the Ca2+ transport system.
Assuntos
Envelhecimento/fisiologia , Cálcio/metabolismo , Contração Miocárdica , Miocárdio/metabolismo , Envelhecimento/metabolismo , Animais , Transporte Biológico , ATPases Transportadoras de Cálcio/metabolismo , Gatos , Cães , Hemodinâmica , Técnicas In Vitro , Mitocôndrias Cardíacas/metabolismo , Músculos Papilares/fisiologia , Coelhos , Ratos , Sarcolema/metabolismo , Retículo Sarcoplasmático/metabolismoRESUMO
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. Alterations in lipid structure, phospholipid composition of membranes and accumulation of free fatty acids appear to be responsible for the phenomenon observed. The increased rate of calcium ions transport found may occur due to alterations in the sarcolemma structure.
Assuntos
Cálcio/metabolismo , Doença das Coronárias/metabolismo , Miocárdio/metabolismo , Sarcolema/metabolismo , Sódio/metabolismo , Doença Aguda , Animais , Transporte Biológico Ativo , Doença das Coronárias/fisiopatologia , Metabolismo dos Lipídeos , Contração Miocárdica , CoelhosRESUMO
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. The found shifts may underlie disturbances in energy supply and a decrease in the contractile myocardium function with ischemia.
Assuntos
Cálcio/metabolismo , Doença das Coronárias/metabolismo , Miocárdio/metabolismo , Absorção , Animais , ATPases Transportadoras de Cálcio/metabolismo , Doença das Coronárias/induzido quimicamente , Membranas Intracelulares/metabolismo , Mitocôndrias Cardíacas/metabolismo , Coelhos , Retículo Sarcoplasmático/metabolismo , VasopressinasRESUMO
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. Changes in erythrocyte calcium concentrations were the greatest in those patients whose myocardial function was disordered considerably.
Assuntos
Doença das Coronárias/fisiopatologia , Contração Miocárdica , Adulto , Cálcio/sangue , ATPases Transportadoras de Cálcio/sangue , Doença das Coronárias/sangue , Eletrocardiografia , Membrana Eritrocítica/enzimologia , Teste de Esforço , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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. A decrease in potassium and an increase in intracellular sodium content as well as a marked decrease in the ratio Ki/Ke were noted. Content of Ca2+ was simultaneously increased 2-2.5-fold in myocardium. These alterations might be responsible for impairment of normal ratios of systole/diastole cycles as well as for a decrease in the contractile functions of myocardium in ischemia.