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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the relative roles of creatine kinase (CK) and adenylate systems in cardiac energy turnover, the effect of CK inhibitor, iodoacetamide- (IAA, 0.5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depletion of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect contractile parameters of the isovolumic heart. However, an augmentation of cardiac work induced by isoproterenol addition was feeble and transient in IAA-treated hearts while the response of DOG-treated hearts was well preserved. The cardiac failure after IAA treatment was associated with irreversible fall in myocardial ATP content as evidenced by 31P-NMR technique. Furthermore, these hearts were unable to perform cardiac pump function due to insufficient cardiac filling and distensibility. The DOG-treated hearts exhibited 50% reduction in the pump function and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function.
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PMID:[Functional significance of 2 pathways of energy transport in cardiomyocytes]. 140 43

The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i, namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol-treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i, namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9-month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6-month-old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose-6-phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate-pressure-product, and a decrease in end-diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P-NMR studies, isoproterenol or isoproterenol + digoxin improved the over-all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate-pressure-product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end-diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts.
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PMID:Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts. 162 50

There is some evidence that exercise intolerance in chronic heart failure is linked to the activity of compensatory mechanisms, including neurohumoral factors. However, there is a lack of correlation between exercise capacity and the degree of LV-dysfunction in this setting. Impaired skeletal muscle perfusion during exercise appears to be involved in reduced exercise capacity in patients with heart failure. The peripheral vasoconstriction mediated by increased sympathetic tone and activated plasma renin-angiotensin-aldosterone system (RAAS) may act primarily for short-term control and its short-term inhibition does not restore exercise capacity. The effects of the vascular RAS, impaired flow-dependent endothelium-mediated dilation (e.g. due to chronically reduced flow) and structural alterations of the vessel wall only slowly emerge over time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased flow to skeletal muscle, because (1) the reversal of the above delineated peripheral alterations develops slowly over time; such agents given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability, (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure; e.g. due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and NMR-spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced exercise tolerance in chronic heart failure and its relationship to neurohumoral factors. 168 Jun 84

Systemic vasoconstriction is a hallmark in chronic heart failure and due to several compensatory mechanisms such as neural, humoral and local vascular factors. Peripheral vasoconstriction mediated by increased sympathetic tone and activated plasma renin-angiotensin system (RAS) may act primarily for short-term control. The effects of the vascular RAS, impaired endothelium-mediated dilation (possibly due to chronically reduced flow) and structural alterations of the vessel wall slowly emerge over time. In addition, fluid and sodium retention may contribute to increase vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropic agents appears to exert redistribution of blood flow without improving blood flow to working muscle during exercise. Even if such agents do improve blood flow to the exercising skeletal muscle with short-term administration, oxygen utilization of the skeletal muscle is not immediately increased because intrinsic abnormalities of skeletal muscle exist in chronic heart failure; e.g. due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle as suggested by ultrastructural analysis and NMR-spectroscopy. The reversal of the above delineated peripheral alterations develop slowly over time. Chronically increased flow may improve impaired endothelium-dependent relaxation of the vessel wall and the oxidative capacity may increase, in part, due to a training effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Peripheral adaptation in chronic heart failure: therapeutic implications]. 182 Mar 1

To address the hypothesis that impaired ATP synthesis rates caused by changes in the creatine kinase system is an important mechanism underlying cardiac failure, we measured total creatine kinase activity, isoenzyme composition and creatine content in two animal models of hypertrophy with cardiac dysfunction, the spontaneously hypertensive rat in the transition to failure and the creatine-depleted hyperthyroid rat heart challenged by hypoxia. During the transition from stable compensated hypertrophy to failure characterized by decreased functional capacity, we found that total creatine kinase activity and particularly mitochondrial creatine kinase activity decreased. The decrease in functional capacity, the further increase in heart size and the derangements in the creatine kinase system did not occur if these animals were treated for 6 months with the antihypertensive agents, guanethidine or hydralazine. These results suggest that changes in the creatine kinase system occur coordinately with the transition to failure. To assess whether the changes in the creatine system may be causally linked to decreased functional capacity, we used 31P NMR spectroscopy of isolated perfused hearts to define the high energy phosphate content and cardiac performance of creatine-depleted (approximately 50%) hypertrophied hearts challenged by hypoxia. These hearts displayed greater susceptibility to hypoxic injury with regard to both systolic and diastolic function during and following hypoxia. We also measured total creatine kinase activity in right ventricular biopsy specimens from patients with various forms of cardiomyopathy and low ejection fractions, and found a positive correlation between total creatine kinase activity and ejection fraction. Taken together, these results support the hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure.
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PMID:Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. 214 77

To study the mechanism of dobutamine on end-stage heart failure, we assessed hemodynamic responses, high-energy phosphates (31P-NMR), and free intracellular calcium ([Ca2+]i) transients (surface fluorometry) during perfusion with 10(-6) mol/L dobutamine in Syrian cardiomyopathic hamsters with severe heart failure. These results were compared to perfusion of the heart with 10(-6) mol/L norepinephrine and 10(-6) mol/L isoproterenol. With the positive inotropic agents the rate-pressure product increased immediately (p less than 0.01 with dobutamine, norepinephrine; p less than 0.003 with isoproterenol); after 10 to 15 minutes of perfusion the rate-pressure product remained relatively stable with norepinephrine and isoproterenol but decreased with dobutamine (p = NS vs control values). [Ca2+]i-transients increased significantly in all groups. The end-diastolic [Ca2+]i decreased continuously with norepinephrine and isoproterenol (p less than 0.008; p less than 0.005) but increased during dobutamine by 19%. Alterations in coronary flow, pHi, high-energy phosphates, and the phosphorylation potential were not significantly different among the three catecholamines. In conclusion, in contrast to norepinephrine and isoproterenol, dobutamine depressed myocardial performance and increased end-diastolic [Ca2+]i in late heart failure.
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PMID:Influence of positive inotropic agents on intracellular calcium transients. Part II. Cardiomyopathic hamster hearts. 258 64

Now that both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have reached their decadic majority, appropriate questions may be asked as to their accomplishments and prognostications for the future. This article emphasizes the approach of the metabolic biologists/physiologists to magnetic resonance biochemistry as indicated by the currently available multinuclear localized approaches. The viewpoint is emphasized that MRS is a critical care instrument where precipitious changes of oxidative metabolism lead to the well-known stroke, heart failure, liver failure, kidney failure, etc. Generally, the gradation between the classical metabolic steady state of life and the pathway leading to cell death is a narrow one and magnetic resonance in some cases is too finely tuned to delineate the gradations of stability and instability of cell metabolism. To this point, magnetic resonance can be supplemented by other modalities that sense tissue distress. An example of a most useful and predictive measure of hypoxic stress is optical spectrophotometry which uses time resolved ranging methods to measure optical path lengths to quantitate hemoglobin deoxygenation in tissues. With such a complement, the two methods emerge as one of general importance in diagnostic procedures.
NMR Biomed 1989 Dec
PMID:What are the goals of magnetic resonance research? 270 5

Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure (peak VO2, 15.4 +/- 4.7 ml/kg/min; ejection fraction, 20 +/- 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers (normal subjects, 22.7 +/- 10.1; heart failure, 33.1 +/- 11.1%; p less than 0.05), atrophy of type IIa (normal subjects, 5,477 +/- 1,109; heart failure, 4,239 +/- 1,247 microns 2; p less than 0.05) and type IIb fibers (normal subjects, 5,957 +/- 1,388; heart failure, 4,144 +/- 945 microns 2; p less than 0.01), and decreased activity of beta-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 +/- 1.44; heart failure, 3.67 +/- 1.68 mol/kg protein/hr; p less than 0.05). No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. 280 70

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.
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PMID:The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency. 321 3

Skeletal muscle bioenergetics of dystrophic hamsters (DH) were studied by in vivo 31P-NMR in order to evaluate possible metabolic impairment. 31P-NMR data were obtained during rest, during muscle work that was induced by nerve stimulation at 3 frequencies (0.2, 0.4 and 1.0 Hz) and during postexercise recovery. At rest, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) was significantly (P less than 0.02) lower in adult DH (5.3 +/- 1.1; +/- 2 SD) compared with control hamsters (6.55 +/- 0.5). An increased PCr depletion was found in DH muscle during nerve stimulation and the steady-state PCr/Pi was significantly (P less than 0.05) lower at 0.4 and 1.0 Hz. Slow PCr/Pi recovery was observed in DH (0.5 +/- 0.2 units per min compared with 1.42 +/- 0.28 for control, +/- 2 SD, P less than 0.02). These findings suggest a significant in vivo mitochondrial malfunction in DH muscle that may result from either mitochondrial abnormalities or cardiac insufficiency or a combination of both.
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PMID:In vivo phosphorus nuclear magnetic resonance (31P-NMR) study of dystrophic hamster muscle. 322 Dec 38


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