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1.
Kardiologiia ; 59(12): 44-51, 2019 Dec 11.
Artigo em Russo | MEDLINE | ID: mdl-31849310

RESUMO

Chronic heart failure (CHF) in most cases is due to a decrease in myocardial contractility. In particular, this results in a reduction in the maximum rate of the pressure development in the left ventricle. At the same time the maximal rate of pressure fall at relaxation is also reduced. This is not surprising, since both depend on Ca ++ myoplasmic concentration. But most of cardiac pathologies have been associated with the impairement of myocardial relaxation to a greater extent than the contraction. In the review a new view has been proposed according to which this phenomenon is attributable to restructuring of titin, the sarcomeric protein that connects the ends of myosin filaments with the sarcomeric board, lines Z. A spring-like molecule of titin shrinks at sarcomeric contraction and straightens in parallel with removing of Ca ++ from myofibrils. A reduction of its stiffness, facilitating the filling of the left ventricle, can reduce restoring force of titin and thereby slow relaxation. The survey provides information about the functions of the calcium transport system and titin in the normal heart and in CHF observed both in experimental models and in patients.


Assuntos
Contração Miocárdica , Miocárdio , Coração , Humanos , Miofibrilas , Sarcômeros
2.
Kardiologiia ; 59(6): 35-41, 2019 Jun 25.
Artigo em Russo | MEDLINE | ID: mdl-31242839

RESUMO

The aim of the study was to ascertain whether the use of plastomitin, the mitochondrial antioxidant, can affect the development of systolic dysfunction that occurs in rats after 4 weeks of doxorubicin treatment (2 mg/kg weekly). Materials and methods. Male Wistar rats weighing 320-380 g were used in this work. Echocardiographic study was carried out using Vevo 1100 with linear probe 13-24 MHz frequency. Results. Echocardiographic study of rats through 8 weeks from the beginning of doxorubicin treatment showed the presence of systolic dysfunction with decrease of ejection fraction of the left ventricle (LV) by 32%. Hearts of rats, to which plastomitin (0.32 mg/kg daily) was administered simultaneously with doxorubicin, showed significantly increased ejection fraction and shortening fraction as compared with doxorubicin group, and these values were close to the control. In experiments with simultaneous registration of LV pressure and volume, it was found that the hearts of all rats treated with doxorubicin showed reduced contractility index and stroke work, while maintaining normal cardiac output. Such compensation in experiments with treatment with doxorubicin alone was achieved through significant reduction in the peripheral resistance, slowing of myocardial relaxation, and facilitation of LV diastolic filling during prolonged diastolic pause (the heart rate was slowed by 23%). In experiments with simultaneous application of doxorubicin and plastomitin, the compensation was achieved through preservation of myocardial contractility and relaxability, the heart rate and peripheral resistance. This method of compensation is more beneficial for the body, because it does not restrict the supply of organs and tissues with oxygen, and has significant advantage over doxorubicin group at equal heart rate. Conclusion. The results allow to conclude that the use of plastomitin together with doxorubicin prevents the development of doxorubicin-induced systolic dysfunction.


Assuntos
Cardiomiopatias , Animais , Antioxidantes , Diástole , Doxorrubicina , Masculino , Ratos , Ratos Wistar , Função Ventricular Esquerda
3.
Kardiologiia ; 59(4): 45-51, 2019 Apr 17.
Artigo em Russo | MEDLINE | ID: mdl-31002039

RESUMO

The Aim of the study was a detailed investigation of pressure volume-loop (PV-loop) curves in the rat heart during development of doxorubicin cardiomyopathy. MATERIALS AND METHODS: Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration (2 mg / kg weekly). RESULTS: Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderance of systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressure and volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole, the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development and stroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normal systolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole. CONCLUSIONS: Based on these data, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolonging myofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolic pause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.


Assuntos
Cardiomiopatias , Disfunção Ventricular Esquerda , Animais , Diástole , Ventrículos do Coração , Ratos , Volume Sistólico , Função Ventricular Esquerda
4.
Kardiologiia ; 58(7): 66-74, 2018 07.
Artigo em Russo | MEDLINE | ID: mdl-30081811

RESUMO

AIM: To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. MATERIALS AND METHODS: Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. RESULTS: Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) compared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. CONCLUSION: The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.


Assuntos
Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/toxicidade , Cardiotônicos/farmacologia , Doença Crônica , Doxorrubicina/toxicidade , Interações de Medicamentos , Ecocardiografia , Coração/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Miocárdio/patologia , Coelhos
5.
Kardiologiia ; (4): 36-44, 2018 Apr.
Artigo em Russo | MEDLINE | ID: mdl-29782258

RESUMO

The aim of the study was comparison of contractile function of isolated hearts of rats with doxorubicin-induced myocardial injury which were tentatively divided according to the level of ejection fraction determined by echocardiography in vivo. After 4 weeks of doxorubicin administration (2 mg/kg subcutaneously once a week) about half of animals had normal (86±1 %) and the other half reduced (61±4 %) ejection fraction. The first group was defined as diastolic heart failure (DHF) and the other as systolic (SHF). The maximal pressure developed by the isolated heart in isovolumic mode was reduced in DHF by 13 %, and in SHF by 34 %. The relaxation index in both groups was lowed by 22-24 %. Both groups were characterized by a decline in the ability to raise developed pressure while increasing coronary perfusion pressure, as well as by the loss of the ability of coronary vessels to maintain a stable flow rate while increasing perfusion pressure. The hearts of control animals were able to raise the cardiac work index (the product of developed pressure and heart rate) during prolonged high frequency (7-9 Hz) stimulation, while the two groups treated with doxorubicin reduced the level of this index. The content of basic energy metabolites (ATP, phosphocreatine, creatine) in both groups was reduced by 20-38 %. The results showed that the hearts in DHF and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms.


Assuntos
Contração Miocárdica , Miocárdio , Animais , Ratos , Volume Sistólico
6.
Kardiologiia ; 58(4): 36-44, 2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-30704381

RESUMO

The aim of the study was comparison of contractile function of isolated hearts of rats with doxorubicin-induced myocardial injury which were tentatively divided according to the level of ejection fraction determined by echocardiography in vivo. After 4 weeks of doxorubicin administration (2 mg/kg subcutaneously once a week) about half of animals had normal (86±1%) and the other half reduced (61±4%) ejection fraction. The first group was defined as diastolic heart failure (DHF) and the other as systolic (SHF). The maximal pressure developed by the isolated heart in isovolumic mode was reduced in DHF by 13%, and in SHF by 34%. The relaxation index in both groups was lowed by 22-24%. Both groups were characterized by a decline in the ability to raise developed pressure while increasing coronary perfusion pressure, as well as by the loss of the ability of coronary vessels to maintain a stable flow rate while increasing perfusion pressure. The hearts of control animals were able to raise the cardiac work index (the product of developed pressure and heart rate) during prolonged high frequency (7-9 Hz) stimulation, while the two groups treated with doxorubicin reduced the level of this index. The content of basic energy metabolites (ATP, phosphocreatine, creatine) in both groups was reduced by 20-38%. The results showed that the hearts in DHF and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms.


Assuntos
Coração , Disfunção Ventricular Esquerda , Animais , Contração Miocárdica , Miocárdio , Fosfocreatina , Ratos , Volume Sistólico , Sístole
7.
Kardiologiia ; (1): 59-64, 2017 Jan.
Artigo em Russo | MEDLINE | ID: mdl-28290834

RESUMO

The anthracycline-induced cardiomyopathy is a frequent and menacing complication of antitumor therapy leading to chronic heart failure. A study of the formation of heart failure can reveal early signs of the development of systolic dysfunction of the heart. In this work in rats we studied cardiac function at different duration of doxorubicin treatment, the most effective anthracycline antibiotic. Cumulative doses of doxorubicin were 8-20 mg/kg, and the term of study lasted from 6 to 20 weeks. The echocardiography and catheterization of the left ventricle (LV) have been use. The ejection fraction and other indicators of LV contractility decreased steadily with increasing dose and duration of the study, in parallel with rat survival. However, the cardiac output related to the unit of body weight, as well as diastolic LV size, remained at a level close to control within 8-10 weeks. Only after 20 weeks when the ejection fraction decreased from 81+/-1 to 49+/-4%, diastolic LV volume increased by 59%. Invasive indicators of myocardial contractility and relaxability significantly decreased by 11 and 19% after doxorubicin dose of 8 mg/kg, while time of preejection and time of systole increased by 18 and 10%. These changes progressed with increasing doses of doxorubicin. At each dose, the relaxation constant declined relatively deeper than contractility index by 8-25%. The results show that: 1) the gradual formation of cardiac insufficiency mobilizes a variety of compensatory mechanisms that retard cardiac dilatation; 2) the development of systolic dysfunction takes place with a predominantly violation of relaxation process; 3) an elongation of the preejection period and duration of systole may serve as noninvasive criteria for the formation of the systolic dysfunction.


Assuntos
Cardiomiopatias , Disfunção Ventricular Esquerda , Animais , Diástole , Doxorrubicina , Coração , Ratos , Volume Sistólico , Sístole
8.
Kardiologiia ; 55(6): 54-62, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26625520

RESUMO

Introduction of isoproterenol (beta-adrenoreceptor agonist) into rats is one of the widespread experimental models of heart failure. It is caused by diffuse ischemic damage of cardiomyocytes, followed by development of substitutive fibrosis. Apelin is a natural regulator of the myocardial contractility. The effects of apelin molecule fragment, apelin-12 and its more stable synthetic analogue, apelin-12-2 on cardiac contractile function of rats with isoproterenol-induced myocardial lesion (IML) and control animals has been studied in this work using invasive (catheterization of the left ventricle) and non-invasive (echocardiography and impedansometry) methods. Infusion of both peptides was made by sequentially increasing rate from 0.5 to 50 µg/kg/min. In the control group, efficacy of apelin-12 was low while apelin-12-2 moderately but significantly increased indices of myocardial contractility and relaxability. These changes were more pronounced in rats with IML and, in addition, the heart rate and LV systolic pressure increased in this group. These results correlate well with echocardiographic studies which showed increases of LV end diastolic volume, stroke volume and ejection fraction by 17-38%. These alterations are probably due to improved Ca2+ transport in cardiomyocytes, as in experiments on isolated cardiomyocytes both apelins have facilitated and improved Ca2+ removal from myoplasma. The results allow to conclude that apelin-12-2 seems to be a promising candidate for further development as a therapeutic agent in heart failure.


Assuntos
Hemodinâmica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Animais , Modelos Animais de Doenças , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Wistar
9.
Kardiologiia ; 55(1): 37-42, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26050488

RESUMO

Prolonged hypotensive effect of oxacom (dinitrosyl iron complexes with ligand glutathione) has been well documented in animals and healthy volunteers, but effect on the heart is not defined. In this work, the blood pressure (BP), and the pressure in the left ventricle (LV) were recorded in rats. Intravenous bolus injection of oxacom (10 mg/kg) caused an immediate average BP decrease by 20-30 mm Hg followed by a slow recovery. The LV systolic and diastolic pressures did not change, but the maximal speed of pressure development, and contractility index at peak action of oxacom increased by 26-33%, while isovolumic relaxation constant fell by 30%. These changes gradually normalized within 10-15 minutes. Effect of oxacom on hearts with isoproterenol-induced diffuse ischemic myocardial lesions and diastolic heart failure was similar to that observed in the control group except the isovolumic relaxation constant rose 1.5-fold while elevated LV diastolic pressure fell. Results suggest that oxacom exerts the positive cardiotropic action especially at heart failure.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Ferro/administração & dosagem , Contração Miocárdica/efeitos dos fármacos , Óxidos de Nitrogênio/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Injeções Intravenosas , Masculino , Ratos , Ratos Wistar
10.
Biochemistry (Mosc) ; 77(11): 1248-57, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23240562

RESUMO

The rhythm of cardiac beats is generated by pacemaker cells differing from other cardiomyocytes by the presence of slow diastolic depolarization. Consistently activated transmembrane ionic currents provide cyclic excitation of pacemakers, forming the original "membrane clocks". A new concept has been forwarded in the last decade according to which periodic fluctuations in myoplasmic Ca2+ level ("calcium clocks") not only influence a course of "membrane clocks", but they also can serve as independent generators of the rhythm. Transport of Ca2+ in cells is under constant influence of active forms of oxygen and nitrogen. Both superoxide and NO in moderate doses facilitate Ca2+ output from the sarcoplasmic reticulum, accelerating the course of "calcium clocks", but in higher doses they have opposite effect that may be neutralized mainly by reduced glutathione. The control of cardiac rhythm by active forms of oxygen and nitrogen represents a feedback mechanism by which mitochondria and NO-synthases support Ca2+ homeostasis in cells that can be temporarily disturbed under mechanical loads or hypoxia.


Assuntos
Coração/fisiologia , Animais , Relógios Biológicos/fisiologia , Cálcio/metabolismo , Humanos , Miocárdio/metabolismo , Óxido Nítrico Sintase/química , Óxido Nítrico Sintase/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Retículo Sarcoplasmático/metabolismo
11.
Acta Naturae ; 2(4): 82-94, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22649668

RESUMO

Bienzyme conjugate was obtained by the covalent connection of superoxide dismutase with catalase through endothelial glycocalyx glycosaminoglycan - chondroitin sulfate (SOD-CHS-CAT). This SOD-CHS-CAT conjugate has vasoprotective activity in respect to platelet interactions, tonus of the ring arterial fragment of a rat blood vessel, as well as normalization of hemodynamic parameters in rats and rabbits in conditions of oxidative stress caused by the administration of hydrogen peroxide. The SOD-CHS-CAT conjugate had antiplatelet potential due to its antiaggregation action manifested through the combination of enzyme activities and an acquired supramolecular structure. The influence on arterial fragment tonus was equivalent for SOD and CAT in native and conjugated form. Blood pressure and heart rate were significant and effectively normalized with SOD-CHS-CAT conjugate in rats and rabbits (after hydrogen peroxide administration as a perturbance stimulus). We have discovered the possibility of using the antioxidant bienzyme conjugate in chronic prophylaxis. It is important for a real development of the oral form of the SOD-CHS-CAT conjugate. These results indicate that the development of enzyme conjugates can be medically significant, as a promising approach for the creation of new drugs.

12.
Biochemistry (Mosc) ; 73(12): 1288-99, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19120015

RESUMO

Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'-plastoquinonyl) decylrhodamine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 micromol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 micromol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.


Assuntos
Envelhecimento , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Nefropatias/tratamento farmacológico , Mitocôndrias/metabolismo , Plastoquinona/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/metabolismo , Transporte Biológico , Doenças Cardiovasculares/metabolismo , Células Cultivadas , Humanos , Técnicas In Vitro , Nefropatias/metabolismo , Masculino , Mitocôndrias/química , Mitocôndrias/efeitos dos fármacos , Plastoquinona/administração & dosagem , Plastoquinona/química , Plastoquinona/metabolismo , Plastoquinona/uso terapêutico , Ratos , Ratos Wistar , Reperfusão , Rodaminas/química , Rodaminas/metabolismo , Rodaminas/uso terapêutico
13.
Biochemistry (Mosc) ; 70(1): 79-84, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15701052

RESUMO

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium. Changes in the antioxidant status of the myocardium induced by long-term addition of coenzyme Q(10) into food was accompanied by decrease in the negative inotropic effect of H2O2, whereas the levels of superoxide dismutase and glutathione peroxidase after oxidative stress were virtually unchanged. The activities of these enzymes displayed a high positive correlation with the cardiac function. The findings suggest that coenzyme Q(10) should increase resistance of the myocardium to oxidative stress not only by a direct antioxidant mechanism but also indirectly, due to increased protection of antioxidant enzymes.


Assuntos
Antioxidantes/metabolismo , Antioxidantes/farmacologia , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Animais , Coenzimas , Peróxido de Hidrogênio , Contração Miocárdica/efeitos dos fármacos , Miocárdio/enzimologia , Oxidantes , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar
14.
Biochemistry (Mosc) ; 69(5): 520-6, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15193126

RESUMO

Ubiquinone Q(10) (coenzyme Q) is an important component of the mitochondrial electron transport chain and an antioxidant. The purpose of this work was to find out whether an increase in the level of coenzyme Q in the heart changes its maximal working capacity and resistance to oxidative stress. Male Wistar rats were treated with coenzyme Q (10 mg/kg body weight per day) for six weeks, and this increased its content in the myocardium by 63%. The myocardial content of malonic dialdehyde and activities of key antioxidant enzymes were unchanged, except nearly 2.5-fold decrease in the activity of superoxide dismutase. The maximal working capacity of the isolated isovolumic heart did not change, but under conditions of oxidative stress induced by 45-min infusion of hydrogen peroxide (70 micro M) into coronary vessels the contractile function of these hearts decreased significantly more slowly. This was associated with less pronounced lesions in the ultrastructure of cardiomyocytes and lesser disorders in the oxidative metabolism of mitochondria that suggested increased antioxidant protection of the myocardium.


Assuntos
Coração/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Miocárdio/metabolismo , Estresse Oxidativo , Ubiquinona/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Citoproteção , Isoproterenol/farmacologia , Masculino , Mitocôndrias/metabolismo , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miocárdio/ultraestrutura , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Ubiquinona/metabolismo
15.
Exp Clin Cardiol ; 6(4): 188-94, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-20428257

RESUMO

BACKGROUND: Precise estimation of the cellular water content presupposes a correct definition of the water fraction in tissue extracellular space. Low molecular weight markers (LMM), such as sulphate ion and sucrose, are widely used to define extracellular space size despite indications that they penetrate the cell. In contrast, inulin, with molecular weight of about 5000, is commonly regarded as a cell impermeable extracellular marker. OBJECTIVES: To compare LMM with inulin as markers in determining extracellular space size. ANIMALS AND METHODS: The size of extracellular space in guinea pig hearts perfused with crystalloid solution (hydrated hearts) was determined morphometrically and by mathematical model analysis of washout kinetics of LMM ((35)SO(4), (14)C-sucrose) or (3)H-inulin. RESULTS: Morphometrically, the sizes of vascular and interstitial spaces in the hydrated hearts were estimated to be 102+/-8 mL/kg wet mass (wm) and 452+/-17 mL/kg wm, respectively. Comparable data were obtained from model simulation of tracer washout: 67 mL/kg wm for vascular space and 439 to 462 mL/kg wm for interstitial space. Tracer penetration into cellular water, as shown by model analysis, was 28% for LMM and, reported here for the first time, 18% for inulin. The observed edema was probably due entirely to fluid accumulation in the interstitial space. CONCLUSION: Intracellular penetration of LMM must be taken into account, especially in modern nuclear magnetic resonance spectroscopic methods of cellular water monitoring in isolated perfused hearts.

16.
Exp Clin Cardiol ; 6(1): 41-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-20428444

RESUMO

The collagen network, part of the myocardial extracellular matrix (EM), and other EM proteins transmit mechanical forces generated by cardiomyocytes to cardiac cavities. Network rearrangement and enlargement - fibrosis - is an essential component of cardiac remodelling at various pathological stages. In particular, similarly abundant fibrosis occurs in dilated, hypertrophic and restrictive cardiomyopathy, and it is unclear how this relates to respective changes in ventricular cavities and size. Recent studies of hereditary forms have provided evidence that, in hypertrophic cardiomyopathy, the primary changes occur within cardiomyocytes that are subjected to either necrosis or mutations in genes that code for contractile proteins, while gene mutations of EM proteins have not been found. In contrast, in dilative cardiomyopathy, gene mutations of dystrophin, merosin and other proteins connecting the collagen matrix to cardiomyocyte membranes and actin filaments have been found. A distortion of the mechanical link between the contractile apparatus and the collagen matrix may disturb force transmission in both directions and lead to decreased developed pressure and increased end-systolic volume, provoking cardiac dilation. Profound alterations in the EM have also been induced acutely by alcohol, adriamycin or a high pacing rate, resulting in the development of dilative cardiomyopathy. Thus, EM alterations may be the primary factor in the pathogenesis of dilative cardiomyopathy.

17.
J Cardiovasc Pharmacol ; 36(5): 669-75, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11065228

RESUMO

The purpose of the study was to explore effects of prolonged caffeine administration on the contractile function and myocardial energy metabolites of the isolated rat heart. Caffeine treatment for 1 week (10 mg/kg, i.p., twice a day) was followed by unchanged pump function of the isolated heart, but reduced maximal left ventricular (LV) systolic pressure by 14% (p < 0.05). Caffeine consumption during 8-9 weeks (0.1% water solution) was also followed by unchanged maximal pump function but increased maximal double product (LV developed pressure multiplied by heart rate) by 23% (p < 0.05). The hearts of caffeine-consumed rats also maintained a higher level of the pump function at a high rate of atrial electrostimulation. The myocardial content of adenosine triphosphate (ATP), creatine phosphate, as well as creatine was slightly but insignificantly increased after caffeine consumption. Results show that in the course of prolonged caffeine treatment, the maximal myocardial contractile function first decreases and then increases, showing adaptation of the heart.


Assuntos
Cafeína/farmacologia , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estimulação Elétrica , Injeções Intraperitoneais , Masculino , Fosfocreatina/metabolismo , Ratos , Ratos Wistar
18.
Am J Physiol ; 275(3): C766-71, 1998 09.
Artigo em Inglês | MEDLINE | ID: mdl-9730960

RESUMO

With the aim of estimating interstitial levels and the breakdown process of ATP, cardiac microdialysis was performed in the left ventricular wall of in situ control and postinfarcted as well as of isolated, Langendorff-perfused rat hearts. With the use of a bioluminescence technique for dialysate ATP measurement, the baseline interstitial fluid ATP concentration in in situ hearts was estimated to be 38 +/- 8 nM. Regional ischemia induced an early peak increase in interstitial fluid ATP to 373 +/- 73 nM that correlates with the maximal incidence of ventricular arrhythmias. During continuous infusion of individual adenine nucleotides (50 microM ATP, ADP, or AMP), the dialysate samples were analyzed for adenine nucleotides, nucleosides, and bases using HPLC with ultraviolet detection. The patterns of catabolites were consistent with the major pathway of metabolism, that is, sequential dephosphorylation catalyzed by a chain of separate ecto-nucleotidases. In in situ postinfarcted hearts as well as in perfused hearts, a reduced catabolism rate of extracellular adenine nucleotides was observed. In conclusion, in in situ rat hearts, ATP can be released in substantial amounts in the interstitium where it readily undergoes enzymatic degradation. Dephosphorylation occurs sequentially and faster in in situ control hearts than in in situ postinfarcted or in perfused hearts.


Assuntos
Trifosfato de Adenosina/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Adenosina/metabolismo , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Animais , Coração/fisiologia , Coração/fisiopatologia , Hipoxantina/metabolismo , Técnicas In Vitro , Inosina/metabolismo , Líquido Intracelular/metabolismo , Masculino , Microdiálise , Contração Miocárdica , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Wistar , Fatores de Tempo , Xantina/metabolismo
19.
Clin Exp Pharmacol Physiol ; 25(1): 10-6, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9493552

RESUMO

1. Metabolic and functional effects of two protocols of preconditioning were compared in rat isolated hearts subjected to 20 min global ischaemia (37 degrees C) and reperfusion (30 min Langendorff + 15 min working). Prior to the ischaemic period, hearts were perfused according to Langendorff (control group) or were preconditioned by three 5 min cycles or two 10 min cycles of ischaemia and reperfusion (PC-I and PC-II groups, respectively). 2. There was no difference in the contractile function between the two preconditioned groups at the onset of sustained ischaemia, although the PC-II group showed enhanced release of adenosine (Ado), inosine, hypoxanthine and xanthine into the interstitium accompanied by losses of tissue adenine nucleotides (sigmaAN = ATP + ADP + AMP), total creatine (sigmaCr = phosphocreatine + creatine) and activation of glycolysis following the preconditioning period. During reperfusion, the PC-I group showed enhanced functional recovery, higher contents of sigmaAN and sigmaCr, and the smallest lactate dehydrogenase release compared with these indices in the control and PC-II groups. Postischaemic myocardial dysfunction was similar in the control and PC-II groups. 3. Functional recovery of hearts in both preconditioned groups was positively correlated with myocardial contents of ATP, sigmaAN and sigmaCr at the end of reperfusion, but not with pre-ischaemic Ado release into the interstitium. The results suggest that pre-ischaemic disturbances of energy metabolism, rather than activation of Ado receptors or stunning, may contribute to efficacy of multiple preconditioning in the rat isolated heart.


Assuntos
Metabolismo Energético , Precondicionamento Isquêmico Miocárdico , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Animais , Espaço Extracelular , Técnicas In Vitro , Precondicionamento Isquêmico Miocárdico/efeitos adversos , L-Lactato Desidrogenase/metabolismo , Masculino , Monitorização Fisiológica , Isquemia Miocárdica/enzimologia , Perfusão , Ratos , Ratos Wistar
20.
Mol Cell Biochem ; 163-164: 131-6, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8974048

RESUMO

The contractile function of the isolated rat heart and high energy phosphate content were evaluated under conditions of depressed energy supply caused by disturbances either in mitochondrial ATP production or ATP-phosphocreatine transformation. Amytal (0.3 mM), an inhibitor of mitochondrial respiration, or iodoacetamide (IAA, 0.1 mM) reducing in this dose creatine kinase activity to 19% of the initial level, were used, respectively. Myocardial ATP content remained unaffected in both groups and PCr content decreased to 37% only in amytal-treated group. Very similar alterations in cardiac pump function during volume load were observed in both treated groups; maximal cardiac output was significantly less by 30%, cardiac pressure-volume work by 38-40%, left ventricular (LV) systolic pressure by 24-29%, and LV +dP/dt by 36-39%. In contrast, the extent of decreased LV distensibility was different, a curve relating LV filling volume and end-diastolic pressure was shifted up and to the left much more prominently after IAA treatment. Heart rate was decreased by 24% only in amytal-treated group. Results indicate that a decreased myocardial distensibility is a dominating feature in the acute cardiac pump failure caused by an inhibition of myocardial creatine kinase. Isoproterenol (0.1 microM) substantially increased heart rate and pressure-rate product in IAA-treated hearts but failed to increase cardiac work probably due to its inability to improve myocardial distensibility.


Assuntos
Amobarbital/farmacologia , Metabolismo Energético , Coração/fisiologia , Iodoacetamida/farmacologia , Isoproterenol/farmacologia , Contração Miocárdica/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Ratos
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