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

  • abnormal cardiac and skeletal muscle Energy metabolism in patients with type 2 diabetes
    Circulation, 2003
    Co-Authors: Michaela Scheuermannfreestone, Stefan Neubauer, George K Radda, Per Lav Madsen, David Neil Manners, Andrew M Blamire, Robin E Buckingham, Peter Styles, K Clarke
    Abstract:

    Background— It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle High-Energy Phosphate metabolism. Methods and Results— We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac High-Energy Phosphate metabolites were measured at rest using 31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle High-Energy Phosphate metabolites, intracellular pH, and oxygenation were measured using 31P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50±0.11, than the healthy volunteers, at 2.30±0.12. The...

  • absolute concentrations of High Energy Phosphate metabolites in normal hypertrophied and failing human myocardium measured noninvasively with 31p sloop magnetic resonance spectroscopy
    Journal of the American College of Cardiology, 2002
    Co-Authors: Meinrad Beer, Kerstin Harre, J Sandstede, Tobias Seyfarth, W Landschutz, Claudia Lipke, Herbert Kostler, Markus Von Kienlin, Dietbert Hahn, Stefan Neubauer
    Abstract:

    Abstract Objectives The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triPhosphate (ATP) in normal, hypertrophied, and failing human heart. Background Conflicting evidence exists on the extent of changes of High-Energy Phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ( 31 P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions. Methods Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by 31 P-MRS with spatial localization with optimum pointspread function. Results Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 ± 1.30 mmol/kg wet weight and 5.69 ± 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 ± 0.33. High-Energy Phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr. Conclusions In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of High-Energy Phosphate levels.

  • mitochondrial creatine kinase is critically necessary for normal myocardial High Energy Phosphate metabolism
    American Journal of Physiology-heart and Circulatory Physiology, 2002
    Co-Authors: Matthias Spindler, M Horn, Reinhard Niebler, Helga Remkes, Titus Lanz, Stefan Neubauer
    Abstract:

    The individual functional significance of the various creatine kinase (CK) isoenzymes for myocardial Energy homeostasis is poorly understood. Whereas transgenic hearts lacking the M subunit of CK (...

  • 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.

  • preservation of left ventricular mechanical function and Energy metabolism in rats after myocardial infarction by the angiotensin converting enzyme inhibitor quinapril
    Journal of Cardiovascular Pharmacology, 1996
    Co-Authors: M Horn, Stefan Neubauer, Stefan Frantz, Stephanie Hugel, Peter Gaudron, Klaus D Schnackerz, Georg Ertl
    Abstract:

    We tested whether angiotensin-converting enzyme (ACE) inhibitor therapy with quinapril prevents the deterioration of mechanical function and High-Energy Phosphate metabolism that occurs in chronically infarcted heart. Rats were subjected to ligation of the left anterior descending coronary artery (LAD) or sham operation. Four groups were studied: sham-operated rats (n = 10), rats with myocardial infarction (MI, n = 9), sham-operated quinapril-treated rats (n = 8), and infarcted quinapril-treated (n = 13) rats. Treated rats received 6 mg/kg/day of the ACE inhibitor quinapril orally, initiated 1 h after MI or sham operation. Eight weeks after LAD ligation or sham operation, hearts were isolated and buffer-perfused isovolumically. High-Energy Phosphate metabolism and intracellular pH were continuously recorded with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hearts were subjected to 15-min control, 30-min hypoxia (95% N2/5% CO2, and 30-min reoxygenation. Left ventricular developed pressure (LVDP) was reduced in infarcted hearts (58 +/- 10 vs. 98 +/- 9 mm Hg in sham, p < 0.05), and this reduction was partially prevented by quinapril (78 +/- 8 mm Hg). ATP content of residual intact myocardium after sham operation or MI was unchanged. Creatine Phosphate was reduced in infarcted hearts (107 +/- 10 vs. 138 +/- 5% of control ATP, p < 0.05), and quinapril prevented this decrease (131 +/- 8%). Therefore, quinapril preserved both function and High-Energy Phosphate metabolism in the chronically infarcted heart. However, when hearts were subjected to acute hypoxia, susceptibility to acute metabolic stress was substantially increased in both quinapril-treated groups: ATP content at end-hypoxia was reduced to 31 +/- 7 and 37 +/- 6% in sham and infarcted quinapril-treated groups, whereas ATP in untreated sham and infarcted hearts was 66 +/- 6 and 66 +/- 3% of baseline values (p < 0.05 untreated vs. quinapril treated). Likewise, recovery of LVDP during reoxygenation was impaired by quinapril treatment (15 +/- 7 and 15 +/- 4 mm Hg in quinapril-treated sham and MI vs. 73 +/- 9 and 46 +/- 9 mm Hg in untreated sham and MI groups, p < 0.05 untreated vs. quinapril treated). The most likely explanation for the unexpected finding of increased susceptibility to acute metabolic stress in the quinapril-treated groups is reduced wall thickness leading to increased wall stress. The preservation of High-Energy Phosphate content in residual intact hearts after MI may contribute to the beneficial effects of ACE inhibitors after MI.

Michael Schocke - One of the best experts on this subject based on the ideXlab platform.

  • cardiac High Energy Phosphate metabolism alters with age as studied in 196 healthy males with the help of 31 phosphorus 2 dimensional chemical shift imaging
    PLOS ONE, 2014
    Co-Authors: Regina Esterhammer, Bernhard Metzler, Christian Wolf, Gert Klug, Agnes Mayr, Sebastian J Reinstadler, Hansjosef Feistritzer, Michael Schocke
    Abstract:

    Recently published studies have elucidated alterations of mitochondrial oxidative metabolism during ageing. The intention of the present study was to evaluate the impact of ageing on cardiac High-Energy Phosphate metabolism and cardiac function in healthy humans. 31-phosphorus 2-dimensional chemical shift imaging (31P 2D CSI) and echocardiography were performed in 196 healthy male volunteers divided into groups of 20 to 40 years (I, n = 43), 40 to 60 years (II, n = 123) and >60 years (III, n = 27) of age. Left ventricular PCr/β-ATP ratio, myocardial mass (MM), ejection fraction and E/A ratio were assessed. Mean PCr/β-ATP ratios were significantly different among the three groups of volunteers (I, 2.10 ± 0.37; II, 1.77 ± 0.37; III, 1.45 ± 0.28; all p<0.001). PCr/β-ATP ratios were inversely related to age (r(2)  =  -0.25; p<0.001) with a decrease from 2.65 by 0.02 per year of ageing. PCr/β-ATP ratios further correlated with MM (r =  -0.371; p<0.001) and E/A ratios (r = 0.213; p<0.02). Moreover, E/A ratios (r =  -0.502, p<0.001), MM (r = 0.304, p<0.001), glucose-levels (r = 0.157, p<0.05) and systolic blood pressure (r = 0.224, p<0.005) showed significant correlations with age. The ejection fraction did not significantly differ between the groups. This study shows that cardiac PCr/β-ATP ratios decrease moderately with age indicating an impairment of mitochondrial oxidative metabolism due to age. Furthermore, MM increases, and E/A ratio decreases with age. Both correlate with left-ventricular PCr/β-ATP ratios. The findings of the present study confirm numerous experimental studies showing an impairment of cardiac mitochondrial function with age.

  • High Energy Phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis
    European Journal of Applied Physiology, 2007
    Co-Authors: Andreas Greiner, Christian Kremser, W Jaschke, Regina Esterhammer, Dietmar Bammer, Hubert Messner, Gustav Fraedrich, Michael Schocke
    Abstract:

    It is known that the relevance of a peripheral stenosis for muscle function increases with exercise. Our intention was to investigate the impact of a moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on High-Energy Phosphate (HEP) metabolism during isotonic, incremental calf exercise. Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity-encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten healthy male volunteers. Each leg underwent four increments of calf exercise (2, 3, 4 and 5 W) followed by recovery during separate exercise sessions with and without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution of 10 s. VEPC MRI was performed at the end of each increment during separate sessions. During all increments, we detected significant differences (P < 0.05) in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis between the sessions without and with CS. Regarding the time courses of the PCr, inorganic Phosphate (Pi) and pH level, we observed significant differences (P < 0.002) during exercise and recovery. During both conditions, the end-increment PCr levels as well as blood flow correlated significantly with the mechanical power. The PCr time constants during exercise significantly correlated with the intramuscular pH, but not with blood flow or mechanical power. However, the PCr recovery time constants correlated significantly with blood flow and end-exercise pH. Our study shows that reduction of blood flow due to a peripheral stenosis results in a prolongation of PCr time constants, decreased PCr and pH level as well as increased Pi level during exercise. We believe that 31P MRS during incremental exercise might provide additional information for assessing the relevance of a peripheral stenosis and its impact on muscle function.

  • High Energy Phosphate metabolism during incremental calf exercise in humans measured by 31 phosphorus magnetic resonance spectroscopy 31p mrs
    Magnetic Resonance Imaging, 2004
    Co-Authors: Michael Schocke, Christian Kremser, W Jaschke, Regina Esterhammer, Gustav Fraedrich, Christian Kammerlander, Anton Rass, Andreas Greiner
    Abstract:

    Several previous 31 phosphorus magnetic resonance spectroscopy ((31)P MRS) studies performing incremental or progressive muscle exercises have observed that a decrease in pH is accompanied with an acceleration in phosphocreatine (PCr) hydrolysis. The purpose of this study was to investigate the relationship between PCr breakdown and pH during isotonic, exhaustive, incremental plantar flexion exercises. We included eight healthy, male volunteers into this study. Using a 1.5 Tesla MR scanner and a self-built exercise bench, we performed serial free induction decay (FID) (31)P MRS measurements with a time resolution of 1 min at rest, isotonic calf muscle exercise, and recovery. The exercise protocol consisted of 5-min intervals with 4.5, 6, 7.5, and 9 W workload followed by 9-min recovery. Changes in PCr and inorganic Phosphate (Pi) were determined as percent changes in comparison to the baseline. In addition, pH values were calculated. This study obtained significant decreases in PCr corresponding to the gradual increases in workload. In each workload level that was succeeded by all volunteers, PCr hydrolysis passed into a steady state. After an early biphasic response, we detected a significant decrease in pH from the first to the second minute of the 6-W workload level followed by a further continuous decrease in pH up to the second minute of the recovery phase. The decrease in pH was not accompanied by acceleration in PCr hydrolysis. In conclusion, this study shows that PCr hydrolysis during incremental plantar flexion exercises passes into a steady state at different workload levels. The observed decrease in pH does not result in acceleration of PCr hydrolysis.

  • impact of aging on cardiac High Energy Phosphate metabolism determined by phosphorus 31 2 dimensional chemical shift imaging 31p 2d csi
    Magnetic Resonance Imaging, 2003
    Co-Authors: Michael Schocke, Bernhard Metzler, Christian Wolf, Peter Steinboeck, Christian Kremser, Otmar Pachinger, W Jaschke, Peter Lukas
    Abstract:

    Previous echocardiographic and experimental animal studies have shown that cardiac function, structure, and metabolism change with age. The aim of this study was to evaluate the impact of age on left ventricular High-Energy Phosphate metabolism. Using a 1.5 Tesla whole-body MR scanner 31P 2D CSI (8 × 8 phase encoding steps, 320 mm field of view) was performed in 76 healthy male volunteers (41.7 ± 13 years) without any history of coronary heart disease. Fourier interpolation, corrections for T1 saturation effects, the nucleus Overhauser effect, and the blood contamination were applied to the spectroscopic data. The volunteers were divided into two groups, younger (n = 37) and older (n = 39) than 41.7 years. In all volunteers, laboratory specimen were sampled, and transthoracal echocardiography was carried out. Significant differences in left ventricular phosphocreatine (PCr) to β-adenosine-triPhosphate (β-ATP) ratios (2.16 vs. 1.83, p < 0.001), fasting serum glucose levels (83.3 vs. 98.7 mg/dl, p < 0.001), E/A (1.51 vs. 1.14 p < 0.001), and ejection fraction (EF, 65.3 vs. 59.9%, p = 0.005) were detected between the two groups of volunteers, younger and older than 41.7 years. Moreover, age correlated moderately to well with left ventricular PCr to β-ATP ratios (r = −0.44), fasting serum glucose levels (r = 0.4), E/A (r = −0.7), left ventricular myocardial mass (r = −0.41), and EF (r = −0.55). In conclusion, our study shows that left ventricular PCr to β-ATP ratios decrease moderately with age, as suggested by previous experimental animal studies. Additionally, age correlates negatively with E/A, left ventricular myocardial mass, and EF, as reported by previous echocardiography studies. The present study is the first to show the impact of age on left ventricular PCr to β-ATP values in humans.

  • decreased High Energy Phosphate ratios in the myocardium of men with diabetes mellitus type i
    Journal of Cardiovascular Magnetic Resonance, 2003
    Co-Authors: Bernhard Metzler, Michael Schocke, Christian Wolf, Peter Steinboeck, Peter Lukas, Werner Judmaier, Monika Lechleitner, Otmar Pachinger
    Abstract:

    Aims / hypothesis: To investigate whether alterations in High-Energy Phosphates occur in the myocardium of persons with diabetes mellitus type I.Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial High-Energy Phosphates have been shown to be reduced by ischemia, and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. Methods: The present study involved 34 male patients (mean age 35.5±10.1) with diabetes mellitus type I and 35 healthy male volunteers (mean age 36±8.6) as age-matched controls. Phosphorus-31 magnetic resonance spectroscopic imaging of the heart was performed in all subjects using a 1.5‐T whole-body magnetic resonance scanner. The ratios of phosphocreatine (PCr) to β-adenosine-triPhosphate (β-ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. Results: The myocardium of patients with diabetes mellitus type I show...

Robert G Weiss - One of the best experts on this subject based on the ideXlab platform.

  • quantification of human High Energy Phosphate metabolite concentrations at 3 t with partial volume and sensitivity corrections
    NMR in Biomedicine, 2013
    Co-Authors: Abdel Monem M Elsharkawy, Robert G Weiss, Refaat E Gabr, Michael Schar, Paul A Bottomley
    Abstract:

    Practical noninvasive methods for the measurement of absolute metabolite concentrations are key to the assessment of the depletion of myocardial metabolite pools which occurs with several cardiac diseases, including infarction and heart failure. Localized MRS offers unique noninvasive access to many metabolites, but is often confounded by nonuniform sensitivity and partial volume effects in the large, poorly defined voxels commonly used for the detection of low-concentration metabolites with surface coils. These problems are exacerbated at Higher magnetic field strengths by greater radiofrequency (RF) field inhomogeneity and differences in RF penetration with heteronuclear concentration referencing. An example is the 31P measurement of cardiac adenosine triPhosphate (ATP) and phosphocreatine (PCr) concentrations, which, although central to cardiac energetics, have not been measured at field strengths above 1.5 T. Here, practical acquisition and analysis protocols are presented for the quantification of [PCr] and [ATP] with one-dimensionally resolved surface coil spectra and concentration referencing at 3 T. The effects of nonuniform sensitivity and partial tissue volumes are addressed at 3 T by the application of MRI-based three-dimensional sensitivity weighting and tissue segmentation. The method is validated in phantoms of different sizes and concentrations, and used to measure [PCr] and [ATP] in healthy subjects. In calf muscle (n = 8), [PCr] = 24.7 ± 3.4 and [ATP] = 5.7 ± 1.3 µmol/g wet weight, whereas, in heart (n = 18), [PCr] = 10.4 ± 1.5 and [ATP] = 6.0 ± 1.1 µmol/g wet weight (all mean ± SD), consistent with previous reports at lower fields. The method enables, for the first time, the efficient, semi-automated quantification of High-Energy Phosphate metabolites in humans at 3 T with nonuniform excitation and detection. Copyright © 2013 John Wiley & Sons, Ltd.

  • exercise induced decrease in myocardial High Energy Phosphate metabolites in patients with chagas heart disease
    Journal of Cardiac Failure, 2013
    Co-Authors: Ana Maria Betim Paes Leme, Robert G Weiss, Vera Maria Cury Salemi, Jose R Parga, Barbara Maria Ianni, Charles Mady, Roberto Kalilfilho
    Abstract:

    Abstract Background The influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. Methods and Results Changes in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with 31 P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac 31 P-MRS. The myocardial phosphocreatine to [β-Phosphate]adenosine triPhosphate ratio (PCr/β-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc–sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/β-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P P P  = NS) in group C. Mean cardiac PCr/β-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P P P Conclusions Myocardial High-Energy Phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac High-Energy Phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.

  • High Energy Phosphate transfer in human muscle diffusion of phosphocreatine
    American Journal of Physiology-cell Physiology, 2011
    Co-Authors: Refaat E Gabr, Abdel Monem M Elsharkawy, Robert G Weiss, Michael Schar, Paul A Bottomley
    Abstract:

    The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a sp...

  • altered High Energy Phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure overload hypertrophy mice
    American Journal of Physiology-heart and Circulatory Physiology, 2007
    Co-Authors: Mikhail Y Maslov, V P Chacko, Matthias Stuber, An L Moens, David A Kass, Hunter C Champion, Robert G Weiss
    Abstract:

    To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and 31P magnetic resonance s...

  • human cardiac High Energy Phosphate metabolite concentrations by 1d resolved nmr spectroscopy
    Magnetic Resonance in Medicine, 1996
    Co-Authors: Paul A Bottomley, Ergin Atalar, Robert G Weiss
    Abstract:

    We have developed a method that can measure High-Energy Phosphate metabolite concentrations in humans with 1D resolved surface-coil NMR spectroscopy. The metabolites are measured by phosphorus (31P) NMR spectroscopy, and the tissue water proton (1H) resonance from the same volume serves as an internal concentration reference. The method requires only the additional acquisition of a 1H data set, and a simple calibration, performed separately, to determine the ratio of the signal per proton to the signal per phosphorus nucleus. The quantification method is particularly useful for human cardiac spectroscopy, where it eliminates image-based tissue volumetry and the corrections for signal sensitivity and phase nonuniformity necessary in prior approaches. Corrections are introduced to account for blood and fat contributions to the spectra. The method was validated on phantoms of Phosphate of varying concentrations and on the human calf muscle. In calf, the adenosine triPhosphate (ATP) and phosphocreatine (PCr) concentrations were 5.6 +/- 1.6 (mean +/- SD) and 26 +/- 4 mmol/kg wet wt, respectively. In normal heart, [ATP] was 5.8 +/- 1.6 and [PCr] was 10 +/- 2 mmol/kg wet wt. These values are in excellent agreement with prior NMR studies and biopsy data. The protocol is easily accommodated within existing 1D cardiac patient protocols, and the same approach is advantageous for eliminating tissue volumetry and sensitivity corrections when measuring concentrations by 2D and 3D resolved spectroscopy.

Paul A Bottomley - One of the best experts on this subject based on the ideXlab platform.

  • fatigability exercise intolerance and abnormal skeletal muscle energetics in heart failure
    Circulation-heart Failure, 2017
    Co-Authors: Kilian Weiss, Paul A Bottomley, Gary Gerstenblith, Michael Schar, Gurusher Panjrath, Yi Zhang, Kavita Sharma, Asieh Golozar, Angela Steinberg, Stuart D Russell
    Abstract:

    Background Among central and peripheral factors contributing to exercise intolerance (EI) in heart failure (HF), the extent to which skeletal muscle (SM) Energy metabolic abnormalities occur and contribute to EI and increased fatigability in HF patients with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively) are not known. An energetic plantar flexion exercise fatigability test and magnetic resonance spectroscopy were used to probe the mechanistic in vivo relationships among SM High-Energy Phosphate concentrations, mitochondrial function, and EI in HFrEF and HFpEF patients and in healthy controls. Methods and Results Resting SM High-Energy Phosphate concentrations and ATP flux rates were normal in HFrEF and HFpEF patients. Fatigue occurred at similar SM energetic levels in all subjects, consistent with a common SM energetic limit. Importantly, HFrEF New York Heart Association class II–III patients with EI and High fatigability exhibited significantly faster rates of exercise-induced High-Energy Phosphate decline than did HFrEF patients with low fatigability (New York Heart Association class I), despite similar left ventricular ejection fractions. HFpEF patients exhibited severe EI, the most rapid rates of High-Energy Phosphate depletion during exercise, and impaired maximal oxidative capacity. Conclusions Symptomatic fatigue during plantar flexion exercise occurs at a common energetic limit in all subjects. HFrEF and HFpEF patients with EI and increased fatigability manifest early, rapid exercise-induced declines in SM High-Energy Phosphates and reduced oxidative capacity compared with healthy and low-fatigability HF patients, suggesting that SM metabolism is a potentially important target for future HF treatment strategies.

  • quantification of human High Energy Phosphate metabolite concentrations at 3 t with partial volume and sensitivity corrections
    NMR in Biomedicine, 2013
    Co-Authors: Abdel Monem M Elsharkawy, Robert G Weiss, Refaat E Gabr, Michael Schar, Paul A Bottomley
    Abstract:

    Practical noninvasive methods for the measurement of absolute metabolite concentrations are key to the assessment of the depletion of myocardial metabolite pools which occurs with several cardiac diseases, including infarction and heart failure. Localized MRS offers unique noninvasive access to many metabolites, but is often confounded by nonuniform sensitivity and partial volume effects in the large, poorly defined voxels commonly used for the detection of low-concentration metabolites with surface coils. These problems are exacerbated at Higher magnetic field strengths by greater radiofrequency (RF) field inhomogeneity and differences in RF penetration with heteronuclear concentration referencing. An example is the 31P measurement of cardiac adenosine triPhosphate (ATP) and phosphocreatine (PCr) concentrations, which, although central to cardiac energetics, have not been measured at field strengths above 1.5 T. Here, practical acquisition and analysis protocols are presented for the quantification of [PCr] and [ATP] with one-dimensionally resolved surface coil spectra and concentration referencing at 3 T. The effects of nonuniform sensitivity and partial tissue volumes are addressed at 3 T by the application of MRI-based three-dimensional sensitivity weighting and tissue segmentation. The method is validated in phantoms of different sizes and concentrations, and used to measure [PCr] and [ATP] in healthy subjects. In calf muscle (n = 8), [PCr] = 24.7 ± 3.4 and [ATP] = 5.7 ± 1.3 µmol/g wet weight, whereas, in heart (n = 18), [PCr] = 10.4 ± 1.5 and [ATP] = 6.0 ± 1.1 µmol/g wet weight (all mean ± SD), consistent with previous reports at lower fields. The method enables, for the first time, the efficient, semi-automated quantification of High-Energy Phosphate metabolites in humans at 3 T with nonuniform excitation and detection. Copyright © 2013 John Wiley & Sons, Ltd.

  • High Energy Phosphate transfer in human muscle diffusion of phosphocreatine
    American Journal of Physiology-cell Physiology, 2011
    Co-Authors: Refaat E Gabr, Abdel Monem M Elsharkawy, Robert G Weiss, Michael Schar, Paul A Bottomley
    Abstract:

    The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a sp...

  • human cardiac High Energy Phosphate metabolite concentrations by 1d resolved nmr spectroscopy
    Magnetic Resonance in Medicine, 1996
    Co-Authors: Paul A Bottomley, Ergin Atalar, Robert G Weiss
    Abstract:

    We have developed a method that can measure High-Energy Phosphate metabolite concentrations in humans with 1D resolved surface-coil NMR spectroscopy. The metabolites are measured by phosphorus (31P) NMR spectroscopy, and the tissue water proton (1H) resonance from the same volume serves as an internal concentration reference. The method requires only the additional acquisition of a 1H data set, and a simple calibration, performed separately, to determine the ratio of the signal per proton to the signal per phosphorus nucleus. The quantification method is particularly useful for human cardiac spectroscopy, where it eliminates image-based tissue volumetry and the corrections for signal sensitivity and phase nonuniformity necessary in prior approaches. Corrections are introduced to account for blood and fat contributions to the spectra. The method was validated on phantoms of Phosphate of varying concentrations and on the human calf muscle. In calf, the adenosine triPhosphate (ATP) and phosphocreatine (PCr) concentrations were 5.6 +/- 1.6 (mean +/- SD) and 26 +/- 4 mmol/kg wet wt, respectively. In normal heart, [ATP] was 5.8 +/- 1.6 and [PCr] was 10 +/- 2 mmol/kg wet wt. These values are in excellent agreement with prior NMR studies and biopsy data. The protocol is easily accommodated within existing 1D cardiac patient protocols, and the same approach is advantageous for eliminating tissue volumetry and sensitivity corrections when measuring concentrations by 2D and 3D resolved spectroscopy.

  • myocardial High Energy Phosphate metabolism and allograft rejection in patients with heart transplants
    Radiology, 1991
    Co-Authors: Paul A Bottomley, Christopher J Hardy, Robert G Weiss, William A Baumgartner
    Abstract:

    To determine whether myocardial High-Energy Phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triPhosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic Phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart).

Matcheri S Keshavan - One of the best experts on this subject based on the ideXlab platform.

  • High Energy Phosphate abnormalities normalize after antipsychotic treatment in schizophrenia a longitudinal 31p mrs study of basal ganglia
    Psychiatry Research-neuroimaging, 2010
    Co-Authors: P N Jayakumar, Matcheri S Keshavan, B N Gangadhar, Ganesan Venkatasubramanian, Sunali Desai, Latha Velayudhan, Dattathreya Subbakrishna
    Abstract:

    Abstract We reported increased High-Energy Phosphate metabolism in the basal ganglia of antipsychotic-naive schizophrenia patients using 31 P Magnetic Resonance Spectroscopy (MRS). These patients were followed up for 1 year and and reassessed using 31 P MRS. Fourteen (8 males) patients with DSM-IV schizophrenia and 14 (11 males) healthy controls underwent 31 P MRS of sub-cortical structures (predominantly basal ganglia) twice (mean±S.D. interscan interval 1.15±0.17year) on a 1.5T scanner. Total scores on the Positive and Negative Syndrome Scale (PANSS) decreased significantly after treatment in schizophrenia patients. Patients had significantly lower mean PCr/ATP ratios than healthy controls at baseline but not during the follow-up. In patients, there was a significant positive correlation between the magnitude of improvement in PANSS total scores and the extent of change in the PCr/ATP ratio. Findings support the hypothesis that reduction of Energy demand or induction of decreased Energy-demanding processes might underlie the mechanism of action of antipsychotics in schizophrenia.

  • basal ganglia High Energy Phosphate metabolism in neuroleptic naive patients with schizophrenia a 31 phosphorus magnetic resonance spectroscopic study
    American Journal of Psychiatry, 2004
    Co-Authors: B N Gangadhar, P N Jayakumar, Dattathreya Subbakrishna, N Janakiramaiah, Matcheri S Keshavan
    Abstract:

    OBJECTIVE: This study used 31-phosphorus magnetic resonance spectroscopy (31P MRS) to investigate basal ganglia abnormalities in neuroleptic-naive patients with schizophrenia. METHOD: Nineteen schizophrenia patients and 31 age- and sex-matched healthy comparison subjects underwent 31P MRS. RESULTS: The phosphocreatine/total phosphorus and phosphocreatine/total ATP ratios in both basal ganglia were significantly lower in patients. CONCLUSIONS: Schizophrenia patients showed features of increased metabolism in the basal ganglia consistent with impaired activity of the frontostriatal pathways.

  • alterations in brain High Energy Phosphate and membrane phospholipid metabolism in first episode drug naive schizophrenics a pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy
    Archives of General Psychiatry, 1991
    Co-Authors: Jay W. Pettegrew, Kanagasabai Panchalingam, Matcheri S Keshavan, Sandra Strychor, David Kaplan, Marjorie Tretta, Maureen Allen
    Abstract:

    • In this pilot study, membrane phospholipid and High-Energy Phosphate metabolism were studied in the dorsal prefrontal cortex of 11 drug-naive, first-episode schizophrenic patients and compared with those of 10 healthy control volunteers comparable in age, education, and parental education. The schizophrenic patients had significantly reduced levels of phosphomonoesters and inorganic orthoPhosphate and significantly increased levels of phosphodiesters and adenosine triPhosphate compared with the controls. The levels of phosphocreatine and adenosine diPhosphate did not differ in the two subject groups. The adenosine triPhosphate and inorganic orthoPhosphate findings suggest functional hypoactivity of the dorsal prefrontal cortex. The phosphomonoester and phosphodiester findings are compatible with either premature aging or an exaggeration of normal programmed regressive events occurring in the neural systems sampled.