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Instability of parasympathetic nerve function evaluated by instantaneous time–frequency analysis in patients with obstructive sleep apnea


The purpose was to determine whether the instability of parasympathetic nerve (PN) function is associated with fragmentation of sleep and the instability can be improved by CPAP treatment in obstructive sleep apnea (OSA). Fifty-three OSA and 50 non-OSA subjects were examined by full-PSG and pulse rate variability (PRV) was recorded simultaneously using a photoplethysmograph and evaluated by instantaneous time–frequency analysis using the complex demodulation method. PN and sympathetic nerve (SN) activity were assessed by the mean high-frequency (HF) amplitude and ratio of low-frequency (LF) and HF amplitude (LF/HF ratio), respectively. Furthermore, the shift in central frequency (CF) of the main HF peak over time was monitored continuously. The relative times over which the same main HF peak was sustained for at least 20 s and 5 min in total recording time (%HF20s and %HF5min) were considered as markers of PN stability. Twenty-two of 53 patients with OSA also examined under the treatment with continuous positive airway pressure (CPAP). A significant increase in mean LF/HF ratio and decrease in HF amplitude were observed in severe OSA. Furthermore, both %HF20s and %HF5min were significantly decreased not only in mild-to-moderate OSA but also in severe OSA, and %HF20s was the strongest independent determinant for arousal index. Treatment with

CPAP significantly decreased the LH/HF ratio and increased both %HF20s and %HF5min. These findings suggest that the stability of PN function is impaired by arousal due to repeated apnea and hypopnea in OSA, and that CPAP therapy improves SN activity and PN dysfunction.

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  1. 1.

    Somers VK. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–904.

    CAS  Article  Google Scholar 

  2. 2.

    Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993;103:1763–8.

    CAS  Article  Google Scholar 

  3. 3.

    Abboud F, Kumar R. Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity. J Clin Invest. 2014;124:1454–7.

    CAS  Article  Google Scholar 

  4. 4.

    Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–84.

    CAS  Article  Google Scholar 

  5. 5.

    Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J. 2006;28:596–602.

    CAS  Article  Google Scholar 

  6. 6.

    Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med. 2005;172:1447–51.

    Article  Google Scholar 

  7. 7.

    Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046–53.

    Article  Google Scholar 

  8. 8.

    Young T, Finn L, Peppard PE, Szkio-Coxe M, Austin D, Nieto FJ, Stubbs R, Hla KM. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31:1071–8.

    Article  Google Scholar 

  9. 9.

    Jurysta F, van de Borne P, Miqeotte PF, Dumont M, Lanquart JP, Deqaute JP, Linkowski P. A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men. Clin Neurophysiol. 2003;114:2146–55.

    CAS  Article  Google Scholar 

  10. 10.

    Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482–92.

    CAS  Article  Google Scholar 

  11. 11.

    Tobaldini E, Nobili L, Strada S, Casali KR, Braghiroli A, Montano N. Heart rate variability in normal and pathological sleep. Front Physiol. 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Szollosi I, Krum H, Kaye D, Nauqhton MT. Sleep apnea in heart failure increases heart rate variability and sympathetic dominance. Sleep. 2007;30:1509–14.

    Article  Google Scholar 

  13. 13.

    Guilleminault V, Connolly S, Winkle R, Melvin K, Tilkian A. Cyclical variation of the heart rate in sleep apnoea syndrome. Mechanisms, and usefulness of 24 h electrocardiography as a screening technique. Lancet. 1984;1:126–31.

    CAS  Article  Google Scholar 

  14. 14.

    Shiomi T, Guilleminault C, Sasanabe R, Hirota I, Maekawa M, Kobayashi T. Augmented very low frequency component of heart rate variability during obstructive sleep apnea. Sleep. 1996;19:370–7.

    CAS  Article  Google Scholar 

  15. 15.

    Keyl C, Lemberqer P, Pfeifer M, Hochmuth K, Geisler P. Heart rate variability in patients with daytime sleepiness suspected of having sleep apnoea syndrome: a receiver-operating characteristic analysis. Clin Sci. 1997;92:335–43.

    CAS  Article  Google Scholar 

  16. 16.

    Berger RD, Saul JP, Cohen RJ. Transfer function analysis of autonomic regulation, 1: canine atrial rate response. Am J Physiol. 1989;256:H142–52.

    CAS  Article  Google Scholar 

  17. 17.

    Jo JA, Blasi A, Valladares E, Juarez R, Baydur A, Khoo MC. Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep. Am J Physiol Heart Circ Physiol. 2005;288:H1103–12.

    CAS  Article  Google Scholar 

  18. 18.

    Chapleau MW, Sabharwal R. Methods of assessing vagus nerve activity and reflexes. Heart Fail Rev. 2011;16:109–27.

    Article  Google Scholar 

  19. 19.

    Hayano J, Taylor JA, Yamada A, Mukai S, Hori R, Asakawa T, Yokoyama K, Watanabe Y, Takata K, Fujinami T. Continuous assessment of hemodynamic control by complex demodulation of cardiovascular variability. Am J Physiol. 1993;264:H1229–38.

    CAS  PubMed  Google Scholar 

  20. 20.

    Hayano J, Taylor JA, Mukai S, Okada A, Watanabe Y, Takata K, Fujinami T. Assessment of frequency shifts in R-R interval variability and respiration with complex demodulation. J Appl Physiol. 1994;77:2879–88.

    CAS  Article  Google Scholar 

  21. 21.

    Yamaguchi K, Ohki N, Kobayashi M, Satoya N, Inoue Y, Onizawa S, Maeda Y, Sekiguchi H, Suzuki M, Tsuji T, Aoshiba K, Nagai A. Estimation of parasympathetic nerve function during sleep in patients with obstructive sleep apnea by instantaneous time-frequency analysis. Sleep Med. 2014;15:33–41.

    Article  Google Scholar 

  22. 22.

    American Academy of Sleep Medicine: International Classification of Sleep Disorders, 3rd edn. Darien, IL, American Academy of Sleep Medicine, 2014.

    Google Scholar 

  23. 23.

    Hayano J, Barros AK, Kamiya A, Ohte N, Yasuma F. Assessment of pulse rate variability by the method of pulse frequency demodulation. Biomed Eng Online 2005, 4:62

  24. 24.

    Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The American academy sleep medicine manual for the scoring of sleep and associated events, rules, terminology and technical specifications. Westchester, IL: American Academy Sleep Medicine; 2007.

    Google Scholar 

  25. 25.

    Hayano J, Yasuma F. Hypothesis: respiratory sinus arrhythmia is an intrinsic resting function of cardiopulmonary system. Cardiovasc Res. 2003;58:1–9.

    CAS  Article  Google Scholar 

  26. 26.

    Roche F, Gaspoz JM, Court-Fortune I, Minini P, Pichot V, Duverney D, Costes F, Lacour JR, Barthelemy JC. Screening of obstructive sleep apnea syndrome by heart rate variability analysis. Circulation. 1999;100:1411–5.

    CAS  Article  Google Scholar 

  27. 27.

    Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;213:220–2.

    CAS  Article  Google Scholar 

  28. 28.

    Task Force of the European Society of Cardiology and the North American Spociety of Pacing Electrophysiology. Circulation. 1996; 93:1043–65.

    Article  Google Scholar 

  29. 29.

    Scholz UJ, Bianchi AM, Cerutti S, Kubicki S. Vegetative background of sleep: spectral analysis of the heart rate variability. Physiol Behav. 1997;62:1037–43.

    CAS  Article  Google Scholar 

  30. 30.

    Werner GG, Ford BQ, Mauss IB, Schabus M, Blechert J, Wilhelm FH. High cardiac vagal control is related to better subjective and objective sleep quality. Biol Physiol. 2015;106:79–85.

    Google Scholar 

  31. 31.

    Yang AC, Tsai SJ, Yang CH, Kuo CH, Chen TJ, Hong CJ. Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia. J Affect Disord. 2011;131:179–85.

    Article  Google Scholar 

  32. 32.

    Gong X, Huang L, Liu X, Li C, Mao X, Liu W, Huang X, Chu H, Wang Y, Wu W, Lu J. Correlation analysis between polysomnography diagnostic indices and heart rate variability parameters among patients with obstructive sleep Apnea Hypopnea syndrome. PLoS One. 2016. Accepted 2 Jun 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Jurysta F, Lanquart JP, van de Borne P, Migeotte PF, Dumont M, Degaute JP, Linkowski P. The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1165–71.

    CAS  Article  Google Scholar 

  34. 34.

    Stein PK, Pu Y. Heart rate variability, sleep and sleep disorders. Sleep Med Rev. 2012;16:47–66.

    Article  Google Scholar 

  35. 35.

    Roche F, Court-Fortune I, Pichot V, Duverney D, Costes F, Emonot A, Vergnon JM, Geyssant A, Lacour JR, Barthélémy JC. Reduced cardiac sympathetic autonomic tone after long-term nasal continuous positive airway pressure in obstructive sleep apnoea syndrome. Clin Physiol. 1999;19:127–34.

    CAS  Article  Google Scholar 

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We thank Toshiro Momose and Haruka Suzuki, polysomnography technicians, and students (Aoki M, Kitagawa M, and Harada M) of the Shinshu University School of Health Sciences for their help and support. This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.


This study did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Keisaku Fujimoto.

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Conflict of interest

The authors did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors, and report no conflicts of interest in this work.

Ethical approval

This study was conducted in accordance with the International Conference on Harmonisation-Good Clinical Practice and the Declaration of Helsinki (2008), and was approved by the institutional research ethics committee of Shinshu University School of Medicine (No. 2099).

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All subjects were given an adequate explanation of the study and provided written informed consent.

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Fujimoto, K., Ura, M., Yamazaki, H. et al. Instability of parasympathetic nerve function evaluated by instantaneous time–frequency analysis in patients with obstructive sleep apnea. Sleep Biol. Rhythms 16, 323–330 (2018).

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  • Autonomic nerve function
  • Obstructive sleep apnea
  • Heart rate variability
  • Photoplethysmograph
  • Continuous positive airway pressure (CPAP)