Phosphorus-31 Two-Dimensional Chemical Shift Imaging in the Myocardium of Patients with Late Onset of Friedreich Ataxia

Wolf, Christian; Boesch, Sylvia; Metzler, Bernhard; Weirich‐Schwaiger, Helga; Trieb, Thomas; Schocke, Michael

doi:10.1007/s11307-007-0119-y

Cited by 4 publications

(2 citation statements)

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“…The pathological cascade in FRDA is not solely restricted to the nervous system. Besides, muscle tissue especially cardiac muscle but also skeletal muscle show decreased frataxin expression and impairment of the respiratory chain [7], [8]. Reduced skeletal muscle adenosine triphosphate (ATP) production and mitochondrial dysfunction could be demonstrated earlier by magnetic resonance spectroscopy (MRS) [9], [10].…”

Section: Introductionmentioning

confidence: 99%

Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by 31P-MRS Before and After Treatment with Recombinant Human Erythropoietin

et al. 2013

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Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO) is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS). Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr) depletion and increased accumulation of inorganic phosphate (Pi) during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.Trial Registration EU Clinical Trials Register 2008-000040-13

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Section: Introductionmentioning

confidence: 99%

Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by 31P-MRS Before and After Treatment with Recombinant Human Erythropoietin

et al. 2013

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“…Previous 31P MRS studies have shown that cardiac PCr/ATP ratios are significantly but unspecifically reduced in ischemic and structural heart diseases [3]–[8] as well as in diabetes and other metabolic disorders [9]–[11]. Furthermore, several previous studies have shown that the cardiac PCr/ATP ratios are clearly reduced in patients suffering from hereditary disorders with mitochondrial involvement [12]–[17].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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 (r2 = −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.

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Idebenone in Friedreich's ataxia

Tonon

Lodi²

2008

Expert Opinion on Pharmacotherapy

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Phosphorus-31 Two-Dimensional Chemical Shift Imaging in the Myocardium of Patients with Late Onset of Friedreich Ataxia

Abstract: In contrast to FRDA patients with early disease onset, our patients collective exhibited a normal, probably compensated cardiac mitochondrial function, whereby IST and EF were mildly altered.

Cited by 4 publications

References 27 publications

Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by 31P-MRS Before and After Treatment with Recombinant Human Erythropoietin

Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by 31P-MRS Before and After Treatment with Recombinant Human Erythropoietin

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

Idebenone in Friedreich's ataxia

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