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V I Veksler

Publications and source records attributed to V I Veksler.

At least 37 records · Page 2Linked to original sources
PubMed1988

Functional state of myofibrils, mitochondria and bound creatine kinase in skinned ventricular fibers of cardiomyopathic hamsters.

Functional states of cardiac contractile apparatus and mitochondria were studied in hereditary cardiomyopathic hamsters (CHF 146) and control golden hamsters using cardiac fibers skinned by two different techniques. The Triton X-100 skinned fibers obtained from diseased animals of 175 to 200 days old, or from control animals, demonstrated the same resting and maximal Ca-activated tensions, the same stiffness, the same rate of tension recovery after quick stretch; the fibers from cardiomyopathic animals differed only by a slightly increased calcium sensitivity. Functional activity of myofibrillar creatine kinase in cardiomyopathy was decreased as indicated by a smaller shift in the pMgATP/rigor tension curve to lower [MgATP] in the presence of phosphocreatine and by a slower rate of the tension recovery after quick stretch in the presence of phosphocreatine and ADP (without ATP). The saponin-skinned fibers allow evaluation of the respiration properties of the total tissue mitochondria. Data obtained in the preparations isolated from diseased animals of two ages (75 to 100 and 175 to 200 days) showed that the ratio of maximal ADP-stimulated respiration rate to the respiration rate in the absence of ADP (an analog of respiration control index) was unchanged in myopathy as compared with age-matched controls. However stimulation of respiration after an addition of creatine at submaximal ADP concentration was observed to be respectively 1.45 times and 3.5 times less in the preparations from younger and older myopathic animals as compared with their respective controls, thus indicating the impairment of functional coupling between mitochondrial creatine kinase reaction and oxidative phosphorylation. These results suggest that hereditary cardiomyopathy is associated with alterations in myocardial creatine kinase system, while myofilaments and mitochondria preserve their basic functional properties.

Adenosine Diphosphate↗
PubMed1988

The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency.

Rats were fed a diet containing beta-guanidinopropionic acid (GP), an inhibitor of creatine transport. After 6 to 8 weeks of feeding the myocardial creatine (Cr) and phosphocreatine (PCr) stores were severely depleted while ATP content was normal. Hearts of GP-treated rats perfused according to Neely's working heart model revealed clear cardiac contractile failure: the maximal work capacity at a stepwise increase in resistance as well as the maximal oxygen consumption were 32 to 40% less in the GP group. The cardiac failure in GP-treated working hearts was associated with a rise in the left ventricular diastolic pressure, which could cause a diminished cardiac output probably due to impaired LV filling. The extent of the contractile failure was found to depend on functional load and on the degree of Cr (PCr) substitution. The energy fluxes through creatine kinase measured by the 31P-NMR saturation transfer technique were diminished by a factor of two after substitution of 90% of creatine, but still exceeded the rate of ATP turnover. The results are compatible with the concept of phosphocreatine pathway for intracellular energy transport and show that PCr is an important high energy phosphate compound for cardiac contractile function.

Animals↗
PubMed1987

Mitochondrial respiratory parameters in cardiac tissue: a novel method of assessment by using saponin-skinned fibers.

Respiratory parameters of cardiac mitochondria were determined in the bundles of cardiac fibers skinned by using saponin that specifically removed sarcolemma, but left intracellular structures intact. In the assay medium which simulated the ion composition of cardiac cytoplasm maximal value of state 3 oxygen consumption per mol cytochromes aa3 was close to that value for isolated mitochondria. Ischemia and isopreterenol treatment were found to affect respiratory parameters of mitochondria in saponin-skinned fibers, among them creatine-stimulated respiration decreased most significantly, (3-4)-times under these conditions. The method described can be easily applied for determination of the mitochondrial respiratory parameters in small (5-10 mg) biopsy samples from human heart.

Animals↗
PubMed1987

[Contractile properties and creatine kinase activity of myofilaments after ischemia and reperfusion of the rat heart].

The state of myofibril creatinkinase and contractile properties of chemically skinned myocardial fibers of rat after 70-90 min ischemia and 15-30 min reperfusion was studied. In spite of sharp fall in the total creatinkinase activity in the tissue, the enzyme activity in myofibrils does not change greatly. Ischemia does not change the functional abilities of myofibril creatinkinase as well as characteristics of Ca-activated contraction of skinned fibers. The results show that irreversible loss of myocardial contractile activity after prolonged ischemia and reperfusion is not connected with violation of myofilament characteristics or deterioration of functional association between myofibril creatinkinase and ATPase.

Actin Cytoskeleton↗
PubMed1987

[Changes in the contractile function and energy metabolism of the isolated heart in chronic adriamycin damage to the myocardium].

4-week administration of adriamycin (20 mg/kg) to rats resulted in the death of approximately one third of the animals, the minute volume of isolated hearts of the surviving animals was less than half of the normal value and the level of phosphocreatine was decreased by one third. The hearts of the rats receiving the same dose of the drug over 10 weeks maintained the same pump function and contained the same amount of macroergic phosphates as those of the control animals. In both series of experiments there was an increase of the end-diastolic pressure and the diastolic elasticity of the left ventricle. In the isovolumic regime the hearts of the rats receiving adriamycin over 10 weeks were able to develop the same pressure only if the rate of coronary blood flow was increased by approximately 1.5 times. Myofibril sensitivity to phosphocreatine deficiency in fibers with destroyed sarcolemma was decreased. The results point to considerable compensatory resources of the heart in chronic adriamycin damage to the myocardium.

Animals↗
PubMed1987

[Calcium binding by chemically stripped fibers of the rat myocardium during force development].

The aim of the study was to measure calcium binding by chemically skinned fibers of rat myocardium during force development at different concentrations of free Ca2+. Fiber fascicles were incubated in the solution with EGTA and 1% X-100 triton for 48 hours to achieve the maximal possible withdrawal of the sarcolemma and intracellular membrane structures. Ca2+ binding was determined using two markers. The fibers started developing a considerable isometric force at pCa 6.2-6.0, the maximal force was registered at pCa 5.0-4.8. At pCa 5.0 the fibers bound 3.59 +/- 0.21 nM of Ca/mg of protein, while at pCa greater than 6 less than one third of this amount was bound. When [Ca2+] was increased to over 1 microM the curve of Ca2+ binding became much steeper and coincided with the curve of force development. The results suggest that Ca2+ binding by myofibrils is evidently cooperative and depends on mechanic tension.

Animals↗
PubMed1986

Heart mitochondria in physiological salt solution: not ionic strength but salt composition is important for association of creatine kinase with the inner membrane surface.

In physiological salt solution (PSS) which mimicks the cardiac cells cytoplasm and contains 120 mM K-MES, 10 mM NaCl, 20 mM imidazole, pH 7.2, 20 mM taurine, 15 mM creatine, 15 mM Na2phosphocreatine, 5 mM Na2ATP, 8 mM MgCl2, 5 mM K2HPO4, 3 mM glutamate, 3 mM malate, 0.5 mM dithiothreitol and 10 mg/ml of bovine serum albumine both isolated mitochondria and intracellular structures in skinned fibers stay intact. In PSS mitochondrial creatine kinase remains firmly attached to the inner membrane surface. CKmi-mi is extracted from cardiac mitoplasts in 0.125 M KCl solution, but addition of 10 mM sodium borate to this KCl solution completely inhibits dissociation of CKmi-mi. Therefore, not ionic strength but ion composition is important for association of CKmi-mi with mitochondrial membrane. Functional and structural studies using antibodies against CKmi-mi showed that in PSS CKmi-mi is bound to the inner mitochondrial membrane in spatially close relationship to adenine nucleotide translocase (ANT). Thus, under physiological conditions CKmi-mi is structurally and functionally coupled to ANT in cardiac mitochondria and functions to catalyze almost complete utilization of mitochondrial ATP for aerobic phosphocreatine synthesis.

Adenosine Diphosphate↗
PubMed1985

[Effect of phosphate and acidosis on the calcium sensitivity of the cardiac myofibrils].

The treatment of the bundles of rat myocardial fibers with ethyleneglycol-bis(beta-aminoethyl ether)-N,N-tetraacetate (EGTA) made the sarcolemma permeable for ions and small molecules. At the incubation medium pH 7.0 the EGTA-treated fibers developed a half-maximal tension at pCa 5.4, and the maximal tension at pCa 4.8. Inorganic phosphate (10 mM) reduced the maximal tension by 18 +/- 3% and decreased the calcium sensitivity of the myofibrils so that there was a shift of the pCa/tension curve by 0.3 unit to the right. Acidosis (pH 6.6) also decreased significantly the calcium sensitivity, while the presence of 10 mM phosphate produced additional depression of the calcium sensitivity. It is concluded that phosphate accumulation by the ischemic myocardium combined with acidosis may depress the contractility not only due to depletion of the free calcium concentration in the myoplasm but also as a result of the reduced calcium sensitivity of myofibrils.

Acidosis↗
PubMed1984

Creatine kinase in regulation of heart function and metabolism. II. The effect of phosphocreatine on the rigor tension of EGTA-treated rat myocardial fibers.

Bundles of rat cardiac fibers were treated with EGTA to increase the permeability of the sarcolemma to ions and small molecules. In the medium without calcium, the EGTA-treated fibers developed rigor tension dependent on the concentration of MgATP in the bathing solution: half-maximal tension was recorded at 2.5 mM MgATP and maximal tension at 0.1 mM MgATP in the medium. However, in the presence of 15 mM phosphocreatine without added creatine kinase a decrease of MgATP concentration to 0.1 mM did not result in any development of rigor tension. Phosphocreatine prevented rigor tension development in the absence of added MgATP when MgADP was added. In the presence of MgADP, phosphocreatine decreased rigor tension more rapidly and to a higher extent than added MgATP. At 5 mM MgADP, half-maximal rigor tension was observed in the presence of 2 mM phosphocreatine which is close to the Km value for phosphocreatine in the creatine-kinase reaction. These results demonstrate that the intact creatine kinase in the EGTA-treated fibers with increased sarcolemmal permeability is able to ensure rapid replenishment of MgATP in the myofibrillar compartment at the expense of phosphocreatine. The data obtained conform completely to the concept of adenine-nucleotide compartmentation in cardiac cells and of energy channelling by the phosphocreatine-creatine shuttle mechanism.

Adenosine Diphosphate↗
PubMed1979

[pH changes and the K+ and Na+ concentration in the blood of the coronary vein in experimental myocardial infarct complicated and not complicated by ventricular fibrillation].

It was found that following occlusion of the coronary artery in dogs, the rate of increase in K+ concentration in blood plasma draining directly from the focus of ischemia is greater in cases complicated by ventricular fibrillation. Fibrillation always occurs against the background of a decrease in pH and an increase in the K+ level in blood plasma draining from the focus of ischemia. It is suggested that inhibition of the development of disorders of acid-base and ion equilibrium in the myocardium would be an effective means of preventing ventricular fibrillation in the acute stage of myocardial infarction.

Acid-Base Imbalance↗
PubMed1979

[Characteristics of the changes in the intra- and extracellular K+ and Na+ concentrations and the intra- and extracellular pH in the area of cardiac ishemia in experimental myocardial infarct complicated by ventricular fibrillation].

Localized ischemia of the heart complicated by ventricular fibrillation is characterized by a tendency to a higher rate of decrease in intra- and extracellular K+ gradient and intracellular pH in the myocardium as compared to cases without fibrillation. The higher rate of K+ escape from the ischemic cells may be linked with a sharper intracellular oxidation, evidence of which is the correlative dependence between the severity of disorders of K+ balance and decrease in intracellular pH in the myocardium in ischemia.

Animals↗
PubMedDate not supplied

Mitochondrial respiration in myocardial biopsy samples as a criterion of postischemic recovery of the cardiac contractility.

Isolated perfused guinea pig hearts were arrested by a high K+ cardioplegic solution containing (PG group) or lacking (control group) 10 mM phosphocreatine + 15 mM glutamate. Total normothermic ischemia lasted 45 min followed by 30 min reperfusion. Mitochondrial respiration in the absence and presence of different concentrations of ADP and creatine was studied in biopsy samples (6-8 mg) after saponin treatment. The samples were taken before and after ischemia, as well as after the reperfusion period. A slightly better relative recovery of developed pressure (RRDP) in PG group was associated with higher mitochondrial acceptor control ratio after reperfusion (5.74 +/- 0.32 vs. 4.54 +/- 0.21 in PG and control groups, resp., p less than 0.01). When the results obtained in both groups were treated together, tight correlations between the pre- or postischemic mitochondrial state and RRDP were revealed. Higher values of RRDP were found for the hearts with lower preischemic values of (low ADP + creatine)-stimulation of mitochondrial respiration (r = -0.57, p less than 0.01). Relative changes in this mitochondrial parameter during ischemic period were in a good correlation with the RRDP (r = 0.82, p less than 0.001). The data suggest that the study of the mitochondrial function in myocardial biopsy samples before ischemia and reperfusion could provide a useful information for the prognosis of cardiac function recovery.

Adenosine Diphosphate↗
PubMedDate not supplied

[Adrenergic stimulation of the heart during inhibition of phosphocreatine or adenylate pathways of energy transfer in cardiomyocytes].

Functional and metabolic response of an isovolumically perfused heart of a rat to isoproterenol (0.1 microM) has been studied. A heart with the normal content of adenine nucleotides (AN) and phosphocreatine (PCr) as well as that with the 5-fold reduced AN content (with 2-deoxyglucose treatment) significantly increased cardiac work index (PRP), maximal contraction rate (MCR) and maximal relaxation rate (MRR) (by 50, 30-40 and 100-150%, respectively). The effect was preserved for all the period of the hormone action (30 min) and was followed by a temporary decrease in the PCr content. The heart with an inhibited unidirectional flux of metabolites through creative kinase (CK) and normal level of AN responded to the hormone by the slower and decelerated growth of the function and in the heart with almost completely iodoacetamide (IAAm)-blocked CK the functional response was minimal and transient. In the latter a significant and irreversible decline in PCr and ATP content and a concomitant rise of inorganic phosphate took place. Both basal and isoproterenol-stimulated adenylate cyclase activity remained unchanged after IAAm treatment. An increase in PRP correlated with the elevation of the cytosolic ADP concentration, however, correlation was not uniform for different experimental groups. These data show significance of the creatine kinase system not only for maintenance of maximal work but also for a rapid functional response to the catecholamine stimulation.

Adenine Nucleotides↗
PubMedDate not supplied

Calcium-dependent changes of the myocardial contractile function at chronic adriamycin treatment.

The contractile function of hearts and atria isolated from rats treated with adriamycin (ADM, total cumulative dose 16-20 mg/kg for 8-10 weeks) was moderately lower as compared to control preparations. However, the former exhibited a relatively higher positive inotropic response to an elevation of Ca++ concentration in the perfusate of isolated hearts or paired pulse stimulation of atria so that maximally attainable values were similar in both groups. On the contrary, the depression of ADM-treated atrial contractile amplitude became even more prominent at moderate increase in stimulation rate and was associated with the apparent incomplete relaxation. Chemically skinned fibers from ADM-treated hearts began to develop force at lower Ca++ concentration and exhibited higher Ca++-sensitivity in pCA range 5.8-5.4. Results suggest that long-term ADM-treatment may be associated with a functional deficiency of Ca++-transporting mechanisms in myocardial cells which may contribute to the depression of the cardiac contractile function.

Animals↗