Impact of Intermittent Hypoxia on Sepsis Outcomes in a Murine Model
Kun-Ta Chou1,2,3,4, Shih-Chin Cheng5,6, Shiang-Fen Huang1,2,7
1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
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.
Insights
Severe intermittent hypoxia (IH), mimicking sleep apnea, worsens sepsis outcomes in mice, leading to increased mortality and inflammation. Mild IH showed minimal impact, and severe IH effects were reversible after normoxic recovery.
Area of Science:
- Physiology
- Pathology
- Sleep Medicine
Background:
- Sleep apnea is linked to various diseases, but its effect on sepsis prognosis is not well understood.
- Intermittent hypoxia (IH) is a key characteristic of sleep apnea.
- Understanding IH's impact on sepsis is crucial for patient outcomes.
Purpose of the Study:
- To investigate the effect of severe and mild intermittent hypoxia (IH) on the outcome of murine sepsis.
- To evaluate the physiological and inflammatory responses to sepsis under IH conditions.
Main Methods:
- Male C57BL6 mice were exposed to severe IH, mild IH, or normoxia for 3 weeks.
- Sepsis was induced using cecal ligation and puncture.
- Survival, bacterial load, inflammatory markers (TNF-α, IL-6), leukocyte count, and organ histopathology were assessed.
Main Results:
- Severe IH significantly increased mortality, bacterial load, and plasma levels of TNF-α and IL-6 compared to normoxic controls.
- Severe IH also led to reduced leukocyte counts and exacerbated inflammatory changes in the lungs, spleen, and intestines.
- Mild IH did not significantly worsen sepsis outcomes, except for a slight increase in IL-6.
- Reversing severe IH with normoxia for 10 days mitigated its adverse effects.
Conclusions:
- Severe intermittent hypoxia, a hallmark of sleep apnea, detrimentally affects sepsis outcomes in mice.
- Mild IH does not appear to significantly impair sepsis outcomes.
- These findings suggest that conditions mimicking sleep apnea can compromise the body's ability to fight sepsis, but this effect may be reversible.
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