Abstract
Sleep apnea has been associated with a variety of diseases, but its impact on sepsis outcome remains unclear. This study investigated the effect of intermittent hypoxia [IH]–the principal feature of sleep apnea–on murine sepsis. 5-week-old male C57BL6 mice were assigned to groups receiving severe IH (O2 fluctuating from room air to an O2 nadir of 5.7% with a cycle length of 90 seconds), mild IH (room air to 12%, 4 minutes/cycle), or room air for 3 weeks. Sepsis was induced by cecal ligation and puncture and survival was monitored. Sepsis severity was evaluated by murine sepsis scores, blood bacterial load, plasma tumor necrosis factor-α [TNF-α]/interleukin-6 [IL-6] levels and histopathology of vital organs. Compared with normoxic controls, mice subjected to severe IH had earlier mortality, a lower leukocyte count, higher blood bacterial load, higher plasma TNF-α and IL-6 levels, more severe inflammatory changes in the lung, spleen and small intestine. Mice subjected to mild IH did not differ from normoxic controls, except a higher IL-6 level after sepsis induced. The adverse impact of severe IH was reversed following a 10-day normoxic recovery. In conclusion, severe IH, not mild IH, contributed to poorer outcomes in a murine sepsis model.
Highlights
Obstructive sleep apnea (OSA) is characterized by frequent pauses in breathing during sleep due to pharyngeal airway collapse
We aimed to investigate whether Intermittent hypoxemia (IH)–the principal component of OSA contributes to poorer outcomes in a murine sepsis model
Prior to Cecal ligation and puncture (CLP), IH1-treated mice had a lower leucocyte count, higher plasma IL-6 and tumor necrosis factor-α (TNF-α) levels compared to controls (p < 0.05, Fig. 3A–C)
Summary
Obstructive sleep apnea (OSA) is characterized by frequent pauses in breathing during sleep due to pharyngeal airway collapse. It affects an estimated 26% of the adult population[1] and has been well-known for its linkage to cardiovascular comorbidities, such as hypertension, coronary artery disease, heart failure and arrhythmia[2,3]. We previously reported that OSA patients have a higher risk of pneumonia[9] and poorer outcomes when confronting sepsis[10]. We aimed to investigate whether IH–the principal component of OSA contributes to poorer outcomes in a murine sepsis model
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