Enhanced Release of Superoxide from Polymorphonuclear Neutrophils in Obstructive Sleep Apnea

TLDR

Obstructive sleep apnea is linked to higher cardiovascular morbidity and mortality, and oxidative free radicals are thought to contribute to cardiovascular disease. The study aimed to test whether heightened oxidative stress underlies the OSA–cardiovascular disease connection. Neutrophil superoxide production was quantified in 18 OSA patients and two control groups using fMLP and A23 stimulation and SOD‑inhibitable cytochrome‑c reduction, with samples taken before and after CPAP therapy and follow‑up. OSA patients exhibited markedly increased neutrophil superoxide release, which was rapidly and almost completely reversed by effective CPAP therapy, indicating neutrophil priming that may drive cardiovascular risk.

Abstract

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Free oxygen radicals have been implicated in the pathogenesis of cardiovascular disorders. Therefore, we aimed to test the hypothesis that increased oxidative stress constitutes one underlying mechanism for the connection between OSA and cardiovascular disease. In 18 patients with OSA the release of superoxide from polymorphonuclear neutrophils was determined after stimulation with the bacterial tripeptide formylmethionylleucylphenylalanine (fMLP) and the calcium ionophore A23. Superoxide production was measured as superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were obtained before and after two nights of CPAP therapy and after 4.8 ± 0.6 mo of follow-up. Ten healthy young volunteers and 10 lung cancer patients without OSA but a similar spectrum of comorbidity served as controls. Before CPAP, neutrophil superoxide generation was markedly enhanced in OSA when compared with both control groups. Effective CPAP therapy led to a rapid and long-lasting decrease of superoxide release in OSA. In conclusion, OSA is linked with a “priming” of neutrophils for enhanced respiratory burst. The increased superoxide generation, which might have major impact on the development of cardiovascular disorders, is virtually fully reversed by effective CPAP therapy.