Abstract
Background and objective
Obstructive sleep apnea (OSA) and heart failure (HF) are common coexisting diseases. Intermittent hypoxia (IH), caused by repeated apnea/hypopnea events, accompanied by increased systemic inflammation, might contribute to the promotion of HF.
Methods
To assess the hypothesis, rats were exposed to IH or normal air condition 4 weeks on the basis of normal heart function or pre-existing HF, which was induced by pressure overload caused by abdominal aortic constriction surgery performed 12 weeks earlier. Echocardiography was performed before and after IH exposure to evaluate left ventricular (LV) function. Serum concentrations of pro-inflammatory cytokines TNF-α and IL-6 were detected by enzyme-linked immunosorbent assay. Flow cytometric analysis was used to determine the apoptotic rate of polymorphonuclear neutrophils (PMNs).
Results
The echocardiographic study showed a significant decrease in LV fractional shortening (FS) and ejection fraction (EF) as well as an increase in the LV relative wall thickness (RWT) index in HF rats, which was aggravated by further exposure to IH compared with single-handed HF-only and sham-IH and sham-control groups. A reduced PMN apoptotic rate was observed in HF-IH rats compared with HF-only, sham-IH, and sham-control rats. Serum concentrations of TNF-α and IL-6 were also increased in HF-IH rats, accompanied by delayed PMN apoptosis, indicating significant systemic inflammation induced by IH.
Conclusion
The results of this study demonstrated that IH aggravates LV remodeling and heart dysfunction in rats with pre-existing HF. Delayed neutrophil apoptosis, which was revealed in HF rats following exposure to IH, contributed to the exacerbation of myocardial damage and progression of heart dysfunction.
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Acknowledgments
This study was supported by the grants from National Natural Science Foundation of China (No. 30800507, 30770934, 30900656)
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None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
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Shuo Li and Jing Feng contributed equally to this work.
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Li, S., Feng, J., Wei, S. et al. Delayed neutrophil apoptosis mediates intermittent hypoxia-induced progressive heart failure in pressure-overloaded rats. Sleep Breath 20, 95–102 (2016). https://doi.org/10.1007/s11325-015-1190-2
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DOI: https://doi.org/10.1007/s11325-015-1190-2