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Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients

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Abstract

Patients with mitochondrial myopathy (MM) have a reduced capacity to perform exercise due to a reduced oxidative capacity. We undertook this study to determine whether skeletal muscle metabolism could be improved with oxygen therapy in patients with MM. Six patients with MM and six controls, matched for age, gender and physical activity, underwent 31P-magnetic resonance spectroscopy (31P-MRS) examination. 31P-MR spectra were collected at rest and in series during exercise and recovery whilst breathing normoxic (0.21 O2) or hyperoxic (1.0 O2) air. At rest, MM showed an elevated [ADP] (18 ± 3 μmol/l) and pH (7.03 ± 0.01) in comparison to the control group (12 ± 1 μmol/l, 7.01 ± 0.01) (P < 0.05) consistent with mitochondrial dysfunction. Oxygen supplementation did not change resting metabolites in either MM or the control group (P > 0.05). Inferred maximal ATP synthesis rate improved by 33% with oxygen in MM (21 ± 3 vs. 28 ± 5 mmol/(l min), P < 0.05) but only improved by 5% in controls (40 ± 3 vs. 42 ± 3 mmol/(l min), P > 0.05). We conclude that oxygen therapy is associated with significant improvements in muscle metabolism in patients with MM. These data suggest that patients with MM could benefit from therapies which improve the provision of oxygen.

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Abbreviations

ATP, [ATP]:

Adenosine triphosphate; cytosolic ATP concentration

ADP, [ADP]:

Adenosine diphosphate; cytosolic ADP concentration

PCr, [PCr]:

Phosphocreatine; cytosolic PCr concentration

CPEO:

Chronic progressive external ophthalmoplegia

\( {{{\text{F}}_{{{\text{IO}}_{{\text{2}}} }} } } \) :

Fraction of inspired oxygen

MELAS:

Mitochondrial encephalopathy lactic acidosis and stroke like episodes

MM:

Mitochondrial myopathy

NIRS:

Near infra-red spectrophotometry

31P-MRS:

Phosphorous magnetic resonance spectroscopy

PCr, [PCr]:

Phosphocreatine; cytosolic PCr concentration

V :

Initial rate of PCr recovery from exercise

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Acknowledgments

MT was supported in part by a Sydney University Nutrition Research Foundation scholarship. This work was supported by a Pacific Healthcare research grant. The authors wish to thank the patients and volunteers for their participation. We would also like to thank Dr. Toos Sachinwalla, Michelle Luong David Walton, and Anita Kipf-Orr for assistance in acquiring MR data.

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Authors and Affiliations

  1. Department of Neurogenetics, Kolling Institute for Medical Research, Sydney, Australia

    Michael I. Trenell & Carolyn M. Sue

  2. School of Molecular and Microbial Bioscience, University of Sydney, Sydney, Australia

    Michael I. Trenell

  3. Department of Medicine, Flinders University of South Australia, Adelaide, SA, Australia

    Campbell H. Thompson

  4. Division of Metabolic and Cellular Medicine, University of Liverpool, Liverpool, UK

    Graham J. Kemp

  5. Newcastle Magnetic Resonance Centre, School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK

    Michael I. Trenell

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  1. Michael I. Trenell
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  2. Carolyn M. Sue
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  3. Campbell H. Thompson
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  4. Graham J. Kemp
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Correspondence to Michael I. Trenell.

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Trenell, M.I., Sue, C.M., Thompson, C.H. et al. Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients. Eur J Appl Physiol 99, 541–547 (2007). https://doi.org/10.1007/s00421-006-0372-9

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