Hypoxic Ventilatory Depression May be Due to Central Chemoreceptor Cell Hyperpolarization

  • John W. Severinghaus
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 393)

Abstract

This paper concerns the possible relationship of the acid secretion found to be localized primarily over the medullary ventral surface CO2 chemosensitive regions to the phenomenon of hypoxic ventilatory depression, HVD, or “roll-off”. HVD occurs between the 5th and 25th minutes of acute steady isocapnic hypoxia in normal man at sea level, eliminating about half of the hypoxic ventilatory stimulus without reducing the slope of the CO2 response curve or central response to a constant stimulus from peripheral chemoreceptors [1–4], recovery requiring similar times [5]. We have demonstrated hypoxic ventilatory depression (HVD) of subjects breathing ambient air, with SaO2-80–90% [6,7]. After 25 min at SpO2 = 75%, when ventilation was apparently depressed by HVD, subjects had normal or above-normal HVR (computed as the differential slope) when SpO2 was rapidly lowered from 75% to 65%.

Keywords

Depression Respiration Adenosine Pyruvate Naloxone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Van Beek, J.H.G.M., A. Berkenbosch, J. DeGoede and C.N. Olievier. Effects of brain stem hypoxaemia on the regulation of breathing. Respiration Physiol 57:171–188, 1984.CrossRefGoogle Scholar
  2. 2.
    Melton, J.E., J. A. Neubauer and N.H. Edelman. CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression. J Appl Physiol 65: 736–743, 1988.PubMedGoogle Scholar
  3. 3.
    Kiwull-Schöene, H and P. Kiwull. Hypoxic modulation of central chemosensitivity. In: Central Neurone Environment, edited by M.E.Schläfke, H.P.Köpfchen and W.R. See. Berlin: Springer Verlag, p.88–95, 1983.Google Scholar
  4. 4.
    Georgopoulos, D., S. Walker, and N. R. Anthonisen. Effect of sustained hypoxia on ventilatory response to CO2 in normal adults. J Appl Physiol 68:891–896, 1990.PubMedGoogle Scholar
  5. 5.
    Easton, P.A., L.J. Slykerman, and N.R. Anthonisen. Recovery of the ventilatory response to hypoxia in normal adults. J Appl Physiol 64:521–528, 1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Sato, M., J.W. Severinghaus, F.L. Powell, F.D. Xu, and M.J. Spellman, Jr. Augmented hypoxic ventilatory response in men at altitude. J Appl Physiol 73: 101–107, 1992.PubMedGoogle Scholar
  7. 7.
    Sato, M, J.W.Severinghaus and P. Bickler. Time course of augmentation and depression of hypoxic ventilatory responses at altitude. J Appl Physiol 76:313–316, 1994.Google Scholar
  8. 8.
    Kagawa, S, M.J.Stafford, T.B.Waggener and J.W.Severinghaus. No effect of naloxone on hypoxia-induced ventilatory depression in adults. J Appl Physiol 52: 1030–1034, 1982.PubMedGoogle Scholar
  9. 9.
    Georgopoulos D, S.G. Holtby, D.Berezanski and N.R.Anthonisen. Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults. J Appl Physiol 67: 1150–1156, 1989.PubMedGoogle Scholar
  10. 10.
    Melton, J.E., J.A. Neubauer and N.H. Edelman. GABA antagonism reverses hypoxic respiratory depression in the cat. J Appl Physiol 69: 1296–1301, 1990.PubMedGoogle Scholar
  11. 11.
    Neubauer J.A., A. Simone and N.H.Edelman. Role of brain lactic acid in hypoxic depression of respiration. J Appl Physiol 65:1324–1331, 1988.PubMedGoogle Scholar
  12. 12.
    Sato M, J.W.Severinghaus, A.I.Basbaum. Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry. J Appl Physiol 73: 96–100, 1992.PubMedGoogle Scholar
  13. 13.
    Xu, F., M.J. Spellman,Jr, M. Sato, J.E. Baumgartner, S. F. Ciricillo and J.W.Severinghaus. Anomalous hypoxic acidification of medullary ventral surface. J. Appl Physiol 71: 221–2217, 1991.Google Scholar
  14. 14.
    Xu, F., M. Sato, M.J. Spellman, Jr, R. A. Mitchell, and J.W. Severinghaus. Topography of cat medullary ventral surface hypoxic acidification. J Appl Physiol 73: 2631–2637, 1992.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • John W. Severinghaus
    • 1
  1. 1.Department of Anesthesia and Cardiovascular Research InstituteUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations