Estimation of Changes in Chemoreflex Gain and ‘Wakefulness Drive’ During Abrupt Sleep-Wake Transitions

  • Steve S. W. Koh
  • Richard B. Berry
  • Jang-Won Shin
  • Michael C. K. Khoo


It is generally accepted that the ventilatory sensitivity to CO2 is decreased during non-rapid eye-movement (NREM) sleep, although the degree of this reduction has varied considerably among studies[1],[2]. In all these studies, the ventilatory response to hypercapnia (HCVR) was measured under steady-state conditions in quiet wakefulness and, subsequently, in one or more stable stages of NREM sleep. In sleep-disordered breathing, however, sleep is constantly punctuated by transient arousals, which are generally associated with brief periods of hyperpnea[3],[4]. Thus, the standard procedures of estimating steady-state chemoresponsiveness may not produce measures that appropriately capture the changes in chemoreflex control that accompany such abrupt state changes. This may partially account for the lack of any consistent relationship between the steady-state HCVR and breathing pattern stability or instability[5].


Ventilatory Response NREM Sleep Central Sleep Apnea Periodic Breathing Mask Pressure 
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  1. 1.
    Phillipson, E.A., and G. Bowes. Control of breathing during sleep. In: Handbook of Physiology, Section 3: The Respiratory System II, Part 2, edited by N.S. Cherniack and J.G. Widdicombe. Bethesda, MD: American Physiological Society, 1986, p.649–690.Google Scholar
  2. 2.
    Stradling, J.R. Handbook of sleep-related breathing disorders. Oford: Oxford Univ. Press, 1993, p. 17–19.Google Scholar
  3. 3.
    Xie, A., B. Wong, E.A. Phillipson, A.S. Slutsky, and T.D. Bradley. Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea. Am. J. Respir. Crit. Med. 150:489–495, 1994.Google Scholar
  4. 4.
    Khoo, M.C.K., J.D. Anholm, S.W. Ko, R. Downey III, A.C.P. Powles, J.R. Sutton, and C.S. Houston. Dynamics of periodic breathing and arousal during sleep at extreme altitude. Respir. Physiol. 103(1): 1–11, 1996.CrossRefGoogle Scholar
  5. 5.
    Chapman, K.R., E.N. Bruce, B. Gothe, and N.S. Cherniack. Possible mechanisms of periodic breathing during sleep. J. Appl. Physiol. 64:1000–1008, 1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Read D.J.C. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann. Med. 16:20–32, 1967.PubMedGoogle Scholar
  7. 7.
    Berthon-Jones, M. and C.E. Sullivan. Ventilation and arousal response to hypercapnia in normal sleeping humans. J. Appl. Physiol. 57: 59–67, 1984.PubMedGoogle Scholar
  8. 8.
    Douglas, N.J., D.P White, J.V. Weil, Cheryl K.P., and C.W. Zwillich. Hypercapnic ventilatory response in sleeping adults. Am. Rev. Respir. Dis. 126:758–762, 1982.PubMedGoogle Scholar
  9. 9.
    Koh S., J.W. Shin, R.B. Berry and M.C.K. Khoo, Assessment of state-chemical drive interaction during abrupt sleep-to-wake transition. Am. J. Respir. Crit. Med. 151:A637, 1995.Google Scholar
  10. 10.
    Shiavi, R. Introduction to Applied Statistical Signal Analysis. Homewood, IL: Aksen, 1991.Google Scholar
  11. 11.
    White, D.P. Occlusion pressure and ventilation during sleep in normal humans. J.Appl. Physiol. 61:1279–1287, 1986.PubMedGoogle Scholar
  12. 12.
    Berry, R.B., K.G. Kouchi, J.L. Bower and R.W. Light. Effect of upper airway anesthesia on obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 151:1857–1861, 1995.PubMedGoogle Scholar
  13. 13.
    Read, D.J.C., and J. Leigh. Blood-brain tissue PCO2 relationships and ventilation during rebreathing. J. Appl. Physiol. 23:53–70, 1967.PubMedGoogle Scholar
  14. 14.
    Hirshman, CA., R.E. McCullough, and J.V. Weil. Normal values for hypoxic and hypercapnic drives in man. J. Appl. Physiol. 38:1095–1098, 1975.PubMedGoogle Scholar
  15. 15.
    Pedley, T.J., R.C. Schroter, and M.F. Sudlow. Gas flow and mixing in the airways. In: Bioengineering Aspects of the Lung, edited by J.B. West. New York: Marcel Dekker, 1977, pp. 163–265.Google Scholar
  16. 16.
    Gleeson, K., C.W. Zwillich and D.P. White. The influence of increasing ventilatory effort on arousal from sleep. Am. Rev. Resp. Dis. 142:295–300, 1990.PubMedGoogle Scholar
  17. 17.
    Khoo, M.C.K., S.S.W. Koh, J.J.W. Shin, PR. Westbrook, and R.B. Berry. Ventilatory dynamics during transient arousal from NREM sleep: Implications for respiratory control stability. J. Appl. Physiol. 80, 1996 80:1475–1484, 1996.PubMedGoogle Scholar
  18. 18.
    Khoo. M.C.K., A. Gottshalk and A.I. Pack. Sleep-induced periodic breathing and apnea: a theoretical study. J. Appl. Physiol. 70: 2014–2024, 1991.PubMedGoogle Scholar
  19. 19.
    Bellville, J.W., W.S. Howland, J.C. Seed, and R.W. Houde. The effect of sleep on the respiratory response to carbon dioxide. Anesthesiology 20:628–634, 1959.PubMedCrossRefGoogle Scholar
  20. 20.
    Khoo, M.C.K. Understanding the dynamics of state-respiratory interaction during sleep: A model-based approach. In: Bioengineering Approaches to Pulmonary Physiology and Medicine, edited by M.C.K. Khoo. New York: Plenum Press, 1996, chap. 1.Google Scholar
  21. 21.
    Berkenbosch, A., J.G. Bovill, A. Dahan, J. DeGoede, and I.C.W. Olievier. The ventilatory CO2 sensitivies from Read’s rebreathing method and the steady state method are not equal in man. J. Physiol. (Lond.) 411:367–377, 1989.Google Scholar
  22. 22.
    Dahan, A., A. Berkenbosch, J. DeGoede, I.C.W. Olievier, and J.G. Bovill. On a pseudo-rebreathing technique to assess the ventilatory sensitivity to carbon dioxide in man. J. Physiol. (Lond.) 423:615–629, 1990.Google Scholar
  23. 23.
    Bellville, J.W., B.J. Whipp, R.D. Kaufmann, G.D. Swanson, K.A. Aqleh, and D.M. Wiberg. Central and peripheral chemoreflex loop gain in normal and carotid body-resected subjects. J. Appl. Physiol. 46:843–853, 1979.PubMedGoogle Scholar

Copyright information

© Plenum Press 1996

Authors and Affiliations

  • Steve S. W. Koh
    • 1
    • 2
  • Richard B. Berry
    • 1
    • 2
  • Jang-Won Shin
    • 1
    • 2
  • Michael C. K. Khoo
    • 1
    • 2
  1. 1.Biomedical Engineering DepartmentUniversity of Southern CaliforniaLos Angeles
  2. 2.Department of MedicineV.A. Medical CenterLong Beach

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