Conformational changes in myocardial actin in heart failure caused by toxic allergic myocarditis

The fluorescence resonance energy transfer method was used to study myocardial actin in rabbits with severe heart failure caused by toxic allergic myocarditis. It caused changes in orientation and microenvironment and increased excitation lifetime of fluorophores at the labels to Cys374 and Cys10 (subdomain 1), as well as at Lys61 and Tyr69 (subdomain 2). In addition, it increased the distance between Cys374 and Lys61, Cys10, and Tyr69, as well as between Tyr69 and Cys10. This attests to enlargement of the outer actin domain and more exposed and open arrangement of the tertiary structures of the N- and C-terminal regions and subdomain 2, accompanied by reduced conformational mobility. The relationships between actin conformation changes and decrease in contractile force and rate, as well as efficiency of actomyosin contraction are revealed, which agrees with the hypothesis on the leading role of actin in disturbances of contractile activity and energy transduction in the system of contractile proteins in heart failure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 395–399, April, 1999     

Three-dimensional structure of thin myocardial filaments in cardiac insufficiency caused by toxic allergic myocarditis

Diffraction patterns of a single myocardial thin filament and its Mg-paracrystals from normal myocardium and in cardiac insufficiency caused by toxic allergic myocarditis were presented, and three-dimensional reconstruction of normal and pathological filaments was carried out. It was shown that in a rigor solution pathological actin protomers are elongated, while normal filaments are kidney-shaped. It is concluded that changes in the thin myocardial filament helix parameters in heart failure caused by toxic allergic myocarditis are due to the loss of conformational mobility of native actin filaments. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 101–105, January, 1999     

Prognostic value of cardiodynamic indexes with respect to the development of heart failure during massive pulmonary embolism

The cardiodynamics of the right ventricle was studied during the first 30 min of massive pulmonary embolism complicated and uncomplicated by heart failure. Both variants were accompanied by diastolic dysfunction of the right ventricle. Some changes in the cardiodynamics observed during complicated massive pulmonary embolism indicated a lower increase in the contractile activity, decreased myocardial contractility, and more pronounced dilation of the right ventricle. The absolute indexes of mechanical activity including indexes of contractility are not reliable criteria for early diagnostics of heart failure in the acute stage of massive pulmonary embolism, whereas changes in these indexes hold much prognostic value. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 634–637, December, 1999     

Effect of sarcolemmal anion transport system blockers on the development of ischemia-induced myocardial edema and recovery of contractile function during reperfusion

Subtotal 30-min ischemia leads to myoglobin release and increases water content in the heart. Reperfusion partially restores the developed pressure. Addition of furosemide (a Na⁺, K⁺, 2Cl⁻-sumport blocker) or NMA (inhibitor of Na⁺/H⁺-exchange) to perfusate decreases myocardial water content, reduces myoglobin loss, and completely restores myocardial contractile function. The low-rate perfusion of isolated heart and its reperfusion with solutions containing DIOA (inhibitor of K⁺, Cl⁻-co-transport) or IAA-94 (Cl⁻ channel blocker) increases water accumulation and myoglobin release from the myocardium, and deteriorated its contractile function during reperfusion. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 400–403, April, 1999     

Role of Actin and Myosin in the Mechanism of the Decrease of Myocardial Contractility and Efficiency of Energy Transformation by Myocardial Myofibrils in Chronic Heart Failure in Humans

Experiments with hybrid myocardial fibers showed that abnormalities of actin (basic protein of fine sarcomer threads) are responsible for reduced contraction rate, decreased developed force, and low efficiency of cardiomyocyte contraction in chronic heart failure caused by dilatation and ischemic cardiomyopathies and infective allergic myocarditis. Wastefulness of the contractile process in cardiomyocyte under conditions of pronounced energy deficit play a key role in progression of chronic heart failure. Hence, actin hypothesis of reduced contractile activity of myocardial contractile protein system in acute heart failure transforms into the actomyosin concept in chronic heart failure.     

心肌收缩蛋白的结构与功能研究进展

心肌收缩蛋白是心肌产生收缩的物质基础。本文介绍了两种主要心肌收缩蛋白：肌凝蛋白和肌动蛋白的结构，尤为详细地讨论了与其功能相关的部分，就正常与异常心脏中两者的改变作一阐述，以期深化心肌肥大和心力衰竭分子水平上的变化认识。     

Effect of polymerization on thermodynamic parameters of melting and stabilization of F-actin structure in normal and dystrophic canine myocardium

Differential scanning microcalorimetry was used to determine changes in enthalpy, entropy, and free energy of melting of purified myocardial fibrillar (F) actin from normal dogs and dogs with 2–3-month L-thyroxin-induced and athyreotic cardiomyopathy. Polymerization of globular (G) actin stabilizes protomer structure in both pathologies. However, the conformational changes in actin monomer caused by L-thyroxin-induced and, especially, by athyreotic cardiomyopathy decrease the free energy of the bonds between protomers in the synthesized F-actin. Binding energy between actin protomers modified in athyreotic cardiomyopathy (−12 kJ/mol) is 4 times below the control value (−48.7 kJ/mol), while in L-thyroxin-induced cardiomyopathy it little differs from the normal value (−40.8 kJ/mol). Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 182–185, August, 1999     

A preliminary course of transauricular electrostimulation mitigates impairment of cardiac contractile function in rats with myocardial infarction

A course of transauricular electrostimulation (TES) consisting of 10 sessions was administered to rats before the induction of myocardial infarction by Selye's method and to rats that were left intact. In the latter anirnals, the electrostimulation did not influence cardiac contractile function at rest (as judged by heart rate, developed pressure, and Katz's index), but exerted beneficial chronotropic and inotropic effects during the maximum isometric tension produced by compression of the ascending aorta. In the TES-pretreated rats with a 2-day-old myocardial infarct, cardiac contractile function was depressed significantly less, both at rest and during isometric tension, than in infarcted rats not exposed to TES. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 568–571, December, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Morphological manifestations of hereditary hypertrophic cardiomyopathy in W/SSM rats

A W/SSM strain of rats with hereditary hypertrophic cardiomyopathy has been created by inbreeding Wistar rats selected for an increased, sensitivity to the cataractogenic effect of high doses of galactose. It is shown that myocardial hypertrophy attended by a diffuse stroma collagenization, focal sclerotic changes, and signs of, chronic heart failure spontaneously develops in these animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 203–207, August, 1994     

Identification,partial sequence and genetic analysis of mlpA,a novel gene encoding a myosin-related protein in Physarum polycephalum

Studies of motility in Physarum polycephalum have concentrated on the well-defined actomyosin system in plasmodia. It is clear from recent genetic studies in lower eukaryotes that myosin is involved in a number of physiological processes in addition to the contractile functions previously asciibed to the classical type II myosins. Moreover, the myosin protein family has proved to be more complex than anticipated, with an increasing number of reported specialized isoforms. Although a myosin type II activity has been identified in both amoebae and plasmodia of P. polycephalum, and it has been inferred that these proteins undergo a phasespecific isoform switch during development, this phenomenon has not been analysed genetically. In an effort to understand the putative developmental expression of actomyosin-associated proteins, we isolated a 180-kDa protein from amoebae which is highly enriched, along with actin and myosin, in actomyosin preparations in the presence of mM concentrations of Mg⁺⁺ ions and 10 mM of ATP. Using polyclonal antisera raised against pl80 we have cloned and sequenced a partial cDNA encoding a protein whose predicted amino-acid sequence indicates some similarity with the Dictyostelium discoideum myosin heavy-chain tail domain. Southern-blot and RFLP analyses indicate that the gene involved, designated mlpA (myosin-like protein), occurs in a single copy in the genome, is a novel Physarum gene and is expressed during amoebal and plasmodial growth and in the dormant forms of both these cell types.     

Changes in rhythmoinotropic reactions of the myocardium in chronic ischemia: Pathology or adaptation?

Changes in the organization of the Ca⁺-transporting systems but not disturbances in the contractile apparatus of cardiomyocytes are shown to occur in chronic coronary heart disease. During a certain stage of CHD the change in rhythmoinotropic relations may reflect adaptive changes induced by functioning of the myocardium under conditions of ischemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 457–459, May, 1994     

Skeletal muscle disorders in heart failure

Heart failure is associated with reduction of exercise capacity that cannot be solely ascribed to reduced maximal oxygen uptake (V˙O_2max). Therefore, research has focused on changes in skeletal muscle morphology, metabolism and function. Factors that can cause such changes in skeletal muscle comprise inactivity, malnutrition, constant or repeated episodes of inadequate oxygen delivery and prolonged exposure to altered neurohumoural stimuli. Most of these factors are not specific for the heart failure condition. On the other hand, heart failure is more than one clinical condition. Congestive heart failure (CHF) develops gradually as a result of deteriorating contractility of the viable myocardium, myocardial failure. Is it possible that development of this contractile deficit in the myocardium is paralleled by a corresponding contractile deficit of the skeletal muscles? This question cannot be answered today. Both patient studies and experimental studies support that there is a switch to a faster muscle phenotype and energy metabolism balance is more anaerobic. The muscle atrophy seen in many patients is not so evident in experimental studies. Few investigators have studied contractile function. Both fast twitch and slow twitch muscles seem to become slower, not faster as might be expected, and this is possibly linked to slower intracellular Ca²⁺ cycling. The neurohumoural stimuli that can cause this change are not known, but recently it has been reported that several cytokines are increased in CHF patients. Thus, the changes seen in skeletal muscles during CHF are partly secondary to inactivity, but the possibility remains that the contractility is altered because of intracellular changes of Ca²⁺ metabolism that are also seen in the myocardium.     

Disorders in the structural and metabolic organization of liver acini in systemic endotoxemia

Injection ofEscherichia coli lipopolysaccharide to dogs caused pronounced structural and metabolic changes of liver acini, characterized by the development of compensatory reactions to the endotoxin followed by their failure. In addition to hypoxia, depressed activity of hepatocyte dehydrogenases and diaphorases with impairment of the intraacinar gradient of their activity, leading to the development of hepatocellular insufficiency, appears to underlie the involvement of the liver in systemic endotoxemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 643–646, December, 1995 Presented by V. V. Kupriyanov, Member of the Russian Academy of Medical Sciences     

Peritoneal endotoxicosis,morphology, and morphogenesis of biosystem involvement in experimental animals

Experimental acute peritonitis was induced by single and repeated injections of 1.5–3% fecal autosuspension in the abdominal cavity of white rats. The blood content of medium-weight molecular proteins, which increases 1.5-2-fold during the course of entry of toxic products into the blood over 1–3 days, was measured. Examination of the vascular system and parenchymatous elements of many organs helped reveal three morphogenetic mechanisms of their injury: hyperfunction of cells, followed by their depletion and death; the direct action of toxic products on membranous structures of cells due to severe impairment of the histohematic barrier at the level of the microcirculation; the destructive effect of hypoxia due to the development of the disseminated intravascular coagulation syndrome. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 636–639, December, 1994 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

Systolic and diastolic functions of the right ventricle during massive pulmonary embolism

Massive pulmonary embolism is accompanied by a sharp increase in the contractile activity of the right ventricle. Cardiodynamics during the first 30 min was characterized as subcompensated with impaired relaxation and then progressed to a compensated state (the next 6 h). The initial stage after a sharp increase in right ventricular afterload under massive pulmonary embolism is a critical period in relation to the development of heart failure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 175–181, August, 1999     

Principal forms of acute damage to cardiomyocytes according to polarization microscopy data

The principal forms of acute cardiomyocyte damage of metabolic and ischemic genesis are accompanied by changes in the contractile apparatus, which is reflected in double refraction of myofibrils. Thus, polarization microscopy is the most sensitive method allowing one to detect the early stages of cardiomyocyte damage. Individual types of cardiomyocyte lesions are identified on the basis of parallel histological studies and polarization and electron microscopy of prenecrotic alterations and myocardial infarction using experimental and autopsy material. They are: I, II, and III degree myofibrillar contracture, intracellular myocytolysis, primary lumpy degradation of myofibrils, and cytolysis. These types of damage form the morphological basis of acute myocardial pathology with a possible outcome of coagulative or colliquative necrosis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 4–13, January, 1996     

Histochemical study of myocardial metabolism in experimental massive pulmonary embolism

The period immediately following massive pulmonary embolism largely determines its further course, that is, whether compensation will occur or whether heart failure will ensue. Prognostically favorable or unfavorable histochemical characteristics of myocardial metabolism during this period are revealed in this study. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 647–650, December, 1995 Presented by V. S. Savel'ev, Member of the Russian Academy of Medical Sciences     

Neisseria gonorrhoeae porin, P.IB, causes release of ATP from yeast actin

Neisserial porins may play a role in the invasion of the host cell by the bacterium. The protein translocates to the host cell membrane and then to the cytosol during the invasive process, and we have shown it interacts with actin in vitro. Here, we have examined the nucleotide-dependence of the interaction of Neisseriaporin, P.IB, with fluorescently labeled yeast G actin. Increasing free ATP between 0 to 0.5 mM retards complex formation between the two proteins. The ATP effect probably results from binding of the nucleotide to actin rather than to porin. Complex formation results in a biphasic release of bound nucleoside triphosphate from actin in the absence of free nucleotide at a rate slower than that of complex formation, but it does not induce hydrolysis of the actin-bound nucleotide. ATP prevents the porin-induced distortion of F-actin structure, and addition of ATP to the complex formed in the absence of free nucleotide induces actin polymerization indicating that P.IB stabilizes nucleotide-free G-actin. Our results suggest that P.IB causes an actin conformation change leading to the production of a polymerization-competent nucleotide-free protein. This revised version was published online in July 2006 with corrections to the Cover Date.     

Measurement of dehydrogenase activity in hepatocytes in massive pulmonary embolism

Experimental massive pulmonary embolism in dogs induces structural and metabolic changes in the liver. The severity of these changes depends on the duration of the postembolization period and the development of heart failure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 635–637, June, 1999     

Na+/H+ countertransport and calcium exchange in peripheral blood cells of healthy subjects and patients with chronic heart failure

A comparative study is performed of Na⁺/H⁺ exchange and Ca²⁻ mobilization in erythrocytes and platelets of patients with stage I–II chronic heart failure caused by dilative cardiomyopathy and ischemic heart disease. A significant rise in the Na⁺/H⁺ exchange rate is found in the cells of chronic heart failure patients, which correlates with an elevated erythrocyte and platelet concentration of Ca²⁺ and an increased “calcium” response of platelets to inductors. The findings testify to a certain functional relationship between various cation-transporting cellular systems whose change in properties upon chronic heart failure can play an important pathogenic role. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 572–575, December, 1994