Background: On the grounds that in patients with obstructive sleep apnea syndrome (OSAS), the external intercostals are chronically exposed to increased inspiratory loading and to continuous hypoxia-reoxygenation cycles, we hypothesized that oxidative stress levels would be increased in those muscles and that treatment with continuous positive airway pressure (CPAP) would modify those levels and improve muscle dysfunction.
Methods: We conducted both a case-control and a case-case study in which reactive carbonyl groups, both malondialdehyde- and hydroxynonenal- (MDA- and HNE-) protein adducts, antioxidant enzyme levels, 3-nitrotyrosine, and fiber type proportions were detected using immunoblotting and immunohistochemistry in the external intercostals of twelve severe OSAS patients (before and after a six-month treatment period with CPAP) and of six control subjects.
Results: As compared to controls, intercostals of OSAS patients showed higher levels of both protein carbonylation (median values 3.06 and 2.45, respectively, p=0.042) and nitration (median values 1.64 and 1.05, respectively, p=0.019), and type I fiber proportions (median values 57% and 48%, respectively, p=0.035), while exhibiting reduced respiratory muscle endurance (median values 3.2 and 9.5 min, respectively, p=0.001). Among all the OSAS patients, positive correlations were found between both MDA- 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) with the apnea-hypopnea index. Although treatment with CPAP significantly improved apnea-hypopnea index and oxygen desaturations, muscle oxidative stress levels or respiratory muscle endurance were not modified.
Conclusions: This study suggests that inspiratory muscle performance is not completely restored after long-term CPAP treatment.
- protein carbonylation and nitration
- respiratory muscle dysfunction