36 research outputs found
Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate
The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGpo′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2 mM/s). Model analyses including Monte Carlo simulation approaches and metabolic control analysis (MCA) showed that this problem could not be amended by model re-parameterization, but instead required reformulation of ADP and Pi feedback control or introduction of additional control mechanisms (feed forward activation), specifically at respiratory Complex III. Both hypotheses were implemented and tested against time course data of phosphocreatine (PCr), Pi and ATP dynamics during post-exercise recovery and validation data obtained by 31P MRS of sedentary subjects and track athletes. The results rejected the hypothesis of regulation by feed forward activation. Instead, it was concluded that feedback control of respiratory chain complexes by inorganic phosphate is essential to explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle throughout its full dynamic range
Muscle Metabolic Responses During Dynamic In-Magnet Exercise Testing : A Pilot Study in Children with an Idiopathic Inflammatory Myopathy
Rationale and Objectives: The clinical utility of supine in-magnet bicycling in combination with phosphorus magnetic resonance spectroscopy (31P MRS) to evaluate quadriceps muscle metabolism was examined in four children with juvenile dermatomyositis (JDM) in remission and healthy age- and gender-matched controls. Materials and Methods: Two identical maximal supine bicycling tests were performed using a magnetic resonance-compatible ergometer. During the first test, cardiopulmonary performance was established in the exercise laboratory. During the second test, quadriceps energy balance and acid/base balance during incremental exercise and phosphocreatine recovery were determined using 31P MRS. Results: During the first test, no significant differences were found between patients with JDM and their healthy peers regarding cardiopulmonary performance. The outcomes of the first test indicate that both groups attained maximal performance. During the second test, quadriceps phosphocreatine and pH time courses were similar in all but one patient experiencing idiopathic postexercise pain. This patient demonstrated faster phosphocreatine depletion and acidification during exercise, yet postexercise mitochondrial adenosine triphosphate synthesis rate measured by phosphocreatine recovery kinetics was approximately twofold faster than control (time constant 23 seconds vs 43 ± 7 seconds, respectively). Conclusions: These results highlight the utility of in-magnet cycle ergometry in combination with 31P MRS to assess and monitor muscle energetic patterns in pediatric patients with inflammatory myopathies
Muscle Metabolic Responses During Dynamic In-Magnet Exercise Testing:A Pilot Study in Children with an Idiopathic Inflammatory Myopathy
Rationale and Objectives: The clinical utility of supine in-magnet bicycling in combination with phosphorus magnetic resonance spectroscopy (P-31 MRS) to evaluate quadriceps muscle metabolism was examined in four children with juvenile dermatomyositis (JDM) in remission and healthy age- and gender-matched controls. Materials and Methods: Two identical maximal supine bicycling tests were performed using a magnetic resonance-compatible ergometer. During the first test, cardiopulmonary performance was established in the exercise laboratory. During the second test, quadriceps energy balance and acid/base balance during incremental exercise and phosphocreatine recovery were determined using P-31 MRS. Results: During the first test, no significant differences were found between patients with JDM and their healthy peers regarding cardiopulmonary performance. The outcomes of the first test indicate that both groups attained maximal performance. During the second test, quadriceps phosphocreatine and pH time courses were similar in all but one patient experiencing idiopathic postexercise pain. This patient demonstrated faster phosphocreatine depletion and acidification during exercise, yet postexercise mitochondrial adenosine triphosphate synthesis rate measured by phosphocreatine recovery kinetics was approximately twofold faster than control (time constant 23 seconds vs 43 +/- 7 seconds, respectively). Conclusions: These results highlight the utility of in-magnet cycle ergometry in combination with P-31 MRS to assess and monitor muscle energetic patterns in pediatric patients with inflammatory myopathies
MRI image with CSI dataset.
<p>T<sub>1</sub> weighted gradient echo image with the measured 2D CSI dataset. The selected voxel in the vastus lateralis muscle with the related <sup>31</sup>P spectrum is shown in yellow.</p
<sup>31</sup>P spectra from a trained and an untrained subject.
<p><sup>31</sup>P spectra from a trained and an untrained subject, after a 3 Hz Lorentzian window function was applied. The Pi<sub>2</sub> intensity is higher in the trained subject. Spectra are scaled to the PCr resonance peak. Peaks visible: two signals for inorganic phosphate (Pi<sub>1</sub> and Pi<sub>2</sub>), glycerol phosphocholine (GPC), glycerol phosphoethanolamine (GPE), phosphocreatine(PCr), γ-adenosine triphosphate (γ-ATP). The inset shown the two signals for inorganic phosphate (Pi<sub>1</sub> and Pi<sub>2</sub>) in the trained and untrained subjects in more detail.</p
Endogenous assessment of diffuse myocardial fibrosis in patients with T1ρ -mapping
PURPOSE: Recently, it was shown that a significantly higher T1ρ is found in compact myocardial fibrosis after chronic myocardial infarction. In this study, we investigated the feasibility of native T1ρ -mapping for the detection of diffuse myocardial fibrosis in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: T1ρ -mapping was performed on three explanted hearts from DCM patients at 3 Tesla (T). Histological fibrosis quantification was performed, and compared with the T1ρ -relaxation times in the heart. Furthermore, twenty DCM patients underwent an MRI at 1.5T. Native T1ρ -maps, native T1 -maps, and extracellular volume (ECV)-maps were acquired. Additionally, eight healthy volunteers were scanned for reference values. RESULTS: A significant correlation (Pearson r = 0.49; P = 0.005) was found between ex vivo T1ρ -values and fibrosis fraction from histology. Additionally, a significantly higher T1ρ -relaxation time (55.2 ± 2.7 ms) was found in DCM patients compared with healthy control subjects (51.5 ± 1.2 ms) (P = 0.0024). The relation between in vivo T1ρ -values and ECV-values was significant (Pearson r = 0.66). No significant relation was found between native T1 - and ECV-values in this study (P = 0.89). CONCLUSION: This study showed proof of principle for the endogenous detection of diffuse myocardial fibrosis with T1ρ -MRI. Ex vivo and in vivo experiments showed promising results that T1ρ -MRI can be used to measure the extent of diffuse myocardial fibrosis in the myocardium
Endogenous assessment of diffuse myocardial fibrosis in patients with T1ρ -mapping
PURPOSE: Recently, it was shown that a significantly higher T1ρ is found in compact myocardial fibrosis after chronic myocardial infarction. In this study, we investigated the feasibility of native T1ρ -mapping for the detection of diffuse myocardial fibrosis in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: T1ρ -mapping was performed on three explanted hearts from DCM patients at 3 Tesla (T). Histological fibrosis quantification was performed, and compared with the T1ρ -relaxation times in the heart. Furthermore, twenty DCM patients underwent an MRI at 1.5T. Native T1ρ -maps, native T1 -maps, and extracellular volume (ECV)-maps were acquired. Additionally, eight healthy volunteers were scanned for reference values. RESULTS: A significant correlation (Pearson r = 0.49; P = 0.005) was found between ex vivo T1ρ -values and fibrosis fraction from histology. Additionally, a significantly higher T1ρ -relaxation time (55.2 ± 2.7 ms) was found in DCM patients compared with healthy control subjects (51.5 ± 1.2 ms) (P = 0.0024). The relation between in vivo T1ρ -values and ECV-values was significant (Pearson r = 0.66). No significant relation was found between native T1 - and ECV-values in this study (P = 0.89). CONCLUSION: This study showed proof of principle for the endogenous detection of diffuse myocardial fibrosis with T1ρ -MRI. Ex vivo and in vivo experiments showed promising results that T1ρ -MRI can be used to measure the extent of diffuse myocardial fibrosis in the myocardium
Bar plot Pi<sub>2</sub>/Pi<sub>1</sub> ratio trained/untrained.
<p>Bar plot of Pi<sub>2</sub>/Pi<sub>1</sub> ratio with a significant higher Pi<sub>2</sub>/Pi<sub>1</sub> in the endurance trained athletes (0.07 ± 0.01) compared to the normal physical active group (0.03 ± 0.01) (P < 0.05).</p
Bar plot of PCr recovery rate trained/untrained.
<p>Bar plot of PCr recovery rate with a significant faster τ<sub>PCr</sub> in the endurance trained athletes (12 ± 3 s) compared to the normal physical active group (24 ± 5 s) (P < 0.05).</p