Article Text

Oxidative stress in the external intercostal muscles of patients with obstructive sleep apnoea
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  1. Esther Barreiro1,
  2. Adam Nowinski2,
  3. Joaquim Gea1,
  4. Pawel Sliwinski2
  1. 1
    Muscle and Respiratory System Research Unit and Respiratory Medicine Department, IMIM-Hospital del Mar, Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), Experimental Sciences and Health Department (CEXS), Universitat Pompeu Fabra, PRBB, Barcelona, Catalonia, Spain
  2. 2
    Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
  1. Dr Esther Barreiro, Muscle and Respiratory System Research Unit, IMIM-Hospital del Mar, Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), Experimental Sciences and Health Department (CEXS), Universitat Pompeu Fabra, PRBB, C/Dr Aiguader 88, E-08003 Barcelona, Spain; ebarreiro{at}imim.es

Abstract

Background: The external intercostal muscles are chronically exposed to increased inspiratory loading and to continuous hypoxia-reoxygenation cycles in patients with obstructive sleep apnoea syndrome (OSAS). It was therefore hypothesised that oxidative stress levels would be increased in these muscles, and that treatment with continuous positive airway pressure (CPAP) would modify the oxidative stress levels and improve muscle dysfunction.

Methods: A case-control study and a case-case study were conducted on the external intercostal muscles of 12 patients with severe OSAS (before and after 6 months of treatment with CPAP) and 6 control subjects. Reactive carbonyl groups, malondialdehyde (MDA)-protein and hydroxynonenal (HNE)-protein adducts, antioxidant enzyme levels, 3-nitrotyrosine and fibre type proportions were measured using immunoblotting and immunohistochemistry.

Results: Compared with controls, the intercostal muscles of patients with OSAS had higher levels of protein carbonylation (median values 3.06 and 2.45, respectively, p = 0.042), nitration (median values 1.64 and 1.05, respectively, p = 0.019) and proportions of type I fibres (median values 57% and 48%, respectively, p = 0.035) and reduced respiratory muscle endurance (median values 3.2 and 9.5 min, respectively, p = 0.001). Positive correlations were found between MDA-protein and HNE-protein adducts (r = 0.641, p = 0.02 and r = 0.594, p = 0.05, respectively) and 3-nitrotyrosine (r = 0.625, p = 0.03) and the apnoea-hypopnoea index (AHI) in all the patients with OSAS. Although treatment with CPAP significantly improved the AHI and oxygen desaturation, muscle oxidative stress levels and respiratory muscle endurance were not affected.

Conclusions: This study suggests that inspiratory muscle performance is not completely restored after long-term treatment with CPAP.

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Footnotes

  • This study was supported by the European Network for the study of clinical and biological implications of Respiratory Muscle failure in patients with Chronic Obstructive Pulmonary Disease (ERESMUS in COPD) (BMTH4-CT98-3406) (EU) and RESPIRA (RTIC C03/11) (Spain).

  • Competing interests: None.

  • Abbreviations:
    AHI
    apnoea-hypopnoea index
    COPD
    chronic obstructive pulmonary disease
    CPAP
    continuous positive airway pressure
    DNP
    2-4 dinitrophenylhydrazone
    ESS
    Epworth sleepiness scale
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    HNE
    hydroxynonenal
    HRP
    horseradish peroxidase
    MDA
    malondialdehyde
    OD
    optical density
    OSAS
    obstructive sleep apnoea syndrome
    PVDF
    polyvinylidene difluoride
    ROS
    reactive oxygen species
    Sao2
    arterial oxygen saturation
    SOD
    superoxide dismutase