Oxidative stress in the external intercostal muscles of patients with obstructive sleep apnoea

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