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Russell S Richardson - One of the best experts on this subject based on the ideXlab platform.

Jeanine J Prompers - One of the best experts on this subject based on the ideXlab platform.

Stefan Neubauer - One of the best experts on this subject based on the ideXlab platform.

  • effects of catecholamine stress on diastolic function and myocardial energetics in obesity
    Circulation, 2012
    Co-Authors: Oliver J Rider, Jane M Francis, Mohammed K Ali, Cameron J Holloway, Tammy J Pegg, M D Robson, Damian J Tyler, James P Byrne, Kieran Clarke, Stefan Neubauer
    Abstract:

    Background—Obesity is characterized by impaired cardiac energetics, which may play a role in the development of diastolic dysfunction and inappropriate shortness of breath. We assessed whether, in obesity, derangement of energetics and diastolic function is further altered during acute cardiac stress. Methods and Results—Normal-weight (body mass index, 22±2 kg/m2; n=9–17) and obese (body mass index, 39±7 kg/m2; n=17–46) subjects underwent assessment of diastolic left ventricular function (cine magnetic resonance imaging volume-time curve analysis) and cardiac energetics (Phosphocreatine/ATP ratio; 31P-magnetic resonance spectroscopy) at rest and during dobutamine stress (heart rate increase, 65±22% and 69±14%, respectively; P=0.61). At rest, obesity was associated with a 22% lower peak filling rate (P<0.001) and a 15% lower Phosphocreatine/ATP ratio (1.73±0.40 versus 2.03±0.28; P=0.048). Peak filling rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio, and Phosphocreatine/ATP ...

  • high energy phosphate metabolism in normal hypertrophied and failing human myocardium
    Heart Failure Reviews, 1999
    Co-Authors: Stefan Neubauer
    Abstract:

    This chapter examines the role of cardiac high-energy phosphate metabolism in normal, hypertrophied and failing human myocardium. Myocardial biopsies allow analysis of ATP, total adenine nucleotides, creatine kinase activity and total creatine content, while non-invasive 31P-magnetic resonance spectroscopy can be used to determine Phosphocreatine/ATP ratios and, most recently, absolute levels of ATP and Phosphocreatine. The failing human myocardium is characterized by reduced Phosphocreatine and total creatine levels, normal or slightly reduced ATP levels and reduced creatine kinase activity. These changes are consistent with, but do not prove, a role of high-energy phosphate metabolism as a contributing factor in heart failure. An answer to the precise functional role of high-energy phosphate metabolism necessitates analysis of free ADP levels, free energy change of ATP hydrolysis and creatine kinase reaction velocity; these measurements may become feasible in coming years. However, analysis of energy metabolism in a compartmentalized manner, i.e., in the compartments relevant for contractile function such as the perimyofibrillar space, will remain elusive for the foreseeable future.

  • effects of chronic dietary creatine feeding on cardiac energy metabolism and on creatine content in heart skeletal muscle brain liver and kidney
    Journal of Molecular and Cellular Cardiology, 1998
    Co-Authors: M Horn, Stefan Frantz, Helga Remkes, Anne Laser, Bert Urban, Andreas Mettenleiter, Klaus D Schnackerz, Stefan Neubauer
    Abstract:

    Little is known about the regulation of total creatine concentration in heart, skeletal muscle, brain, liver and kidney in response to increased dietary creatine intake. The phosphorylated fraction of intracellular creatine (Phosphocreatine) remain relatively constant, and therefore, higher intracellular creatine levels may increase the energy reserve of the heart [Phosphocreatine and phosphoryl transfer via creatine kinase (CK)] and of other organs. To test the effect of supplying exogenous creatine on the myocardial energy reserve and on creatine content of various organs, rats were given chow containing 0 (Untreated), 1, 3, 5, or 7% (of diet weight) creatine for ;40 days. Thereafter, hearts were perfused and left ventricular developed pressure and heart rate were recorded. High-energy phosphate concentrations were determined with 31P-NMR spectroscopy, CK reaction velocity by 31P-magnetization transfer. Total creatine was determined in heart, skeletal muscle, brain, liver, kidney and serum by high-performance liquid chromatography (HPLC). Creatine feeding increased serum creatine by 73% (1% creatine), 142% (3%), 166% (5%) and 202% (7%). In the heart, increased serum creatine levels did not affect mechanical function; ATP, Phosphocreatine, inorganic phosphate, CK reaction velocity and total creatine were all unchanged. Total creatine also remained constant in brain and skeletal muscle, while creatine content increased 4.6-fold in the liver and 1.9-fold in the kidney. We conclude that myocardial energy reserve via CK cannot be increased by exogenous creatine treatment.

  • myocardial Phosphocreatine to atp ratio is a predictor of mortality in patients with dilated cardiomyopathy
    Circulation, 1997
    Co-Authors: Stefan Neubauer, M Horn, Thomas Pabst, Kerstin Harre, Monika Cramer, John B Newell, Werner Peters, Georg Ertl, Dietbert Hahn, Joanne S Ingwall
    Abstract:

    Background In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial Phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the Phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. Methods and Results Thirty-nine patients with dilated cardiomyopathy were followed up for 928±85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac Phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal Phosphocreatine-to-ATP ratio (>1.60; mean±SE, 1.98±0.07; n=19; healthy volunte...

G K Radda - One of the best experts on this subject based on the ideXlab platform.

  • skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood
    Annals of Neurology, 1995
    Co-Authors: Graham J Kemp, D J Taylor, P R J Barnes, Janet A Wilson, G K Radda
    Abstract:

    Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in Phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of Phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of Phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

  • skeletal muscle mitochondrial function studied by kinetic analysis of postexercise Phosphocreatine resynthesis
    Journal of Applied Physiology, 1995
    Co-Authors: Campbell H Thompson, Graham J Kemp, A L Sanderson, G K Radda
    Abstract:

    To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study Phosphocreatine (PCr) recovery in rat leg muscle a...

  • cellular energetics in hypothyroid muscle
    European Journal of Clinical Investigation, 1992
    Co-Authors: D J Taylor, B Rajagopalan, G K Radda
    Abstract:

    . Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of Phosphocreatine/ATP and inorganic phosphate/ATP, while Phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of Phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.

Graham J Kemp - One of the best experts on this subject based on the ideXlab platform.

  • comparing localized and nonlocalized dynamic 31 p magnetic resonance spectroscopy in exercising muscle at 7t
    Magnetic Resonance in Medicine, 2012
    Co-Authors: Graham J Kemp, Martin Meyerspeer, Simon Robinson, Christine Nabuurs, Tom W J Scheenen, Adrian Schoisengeier, Ewald Unger, Ewald Moser
    Abstract:

    By improving spatial and anatomical specificity, localized spectroscopy can enhance the power and accuracy of the quantitative analysis of cellular metabolism and bioenergetics. Localized and nonlocalized dynamic 31P magnetic resonance spectroscopy using a surface coil was compared during aerobic exercise and recovery of human calf muscle. For localization, a short echo time single-voxel magnetic resonance spectroscopy sequence with adiabatic refocusing (semi-LASER) was applied, enabling the quantification of Phosphocreatine, inorganic phosphate, and pH value in a single muscle (medial gastrocnemius) in single shots (TR = 6 s). All measurements were performed in a 7 T whole body scanner with a nonmagnetic ergometer. From a series of equal exercise bouts we conclude that: (a) with localization, measured Phosphocreatine declines in exercise to a lower value (79 ± 7% cf. 53 ± 10%, P = 0.002), (b) Phosphocreatine recovery shows shorter half time (t1/2 = 34 ± 7 s cf. t1/2 = 42 ± 7 s, nonsignificant) and initial postexercise Phosphocreatine resynthesis rate is significantly higher (32 ± 5 mM/min cf. 17 ± 4 mM/min, P = 0.001) and (c) in contrast to nonlocalized 31P magnetic resonance spectroscopy, no splitting of the inorganic phosphate peak is observed during exercise or recovery, just an increase in line width during exercise. This confirms the absence of contaminating signals originating from weaker-exercising muscle, while an observed inorganic phosphate line broadening most probably reflects variations across fibers in a single muscle. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

  • skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood
    Annals of Neurology, 1995
    Co-Authors: Graham J Kemp, D J Taylor, P R J Barnes, Janet A Wilson, G K Radda
    Abstract:

    Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in Phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of Phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of Phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

  • skeletal muscle mitochondrial function studied by kinetic analysis of postexercise Phosphocreatine resynthesis
    Journal of Applied Physiology, 1995
    Co-Authors: Campbell H Thompson, Graham J Kemp, A L Sanderson, G K Radda
    Abstract:

    To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study Phosphocreatine (PCr) recovery in rat leg muscle a...