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Effect of Theophylline on Brain Acid-Base Status during Normoxia and Hypoxia in Humans

  • Masaharu Nishimura
  • Aya Kakinoki
  • Shuichi Kobayashi
  • Makoto Yamamoto
  • Yasushi Akiyama
  • Kenji Miyamoto
  • Yoshikazu Kawakami

Abstract

Theophylline, a methylxanthine, is known to stimulate ventilation and augment the ventilatory response to hypoxia in humans by several proposed mechanisms.1, 2 Since theophylline, an adenosine receptor antagonist, has been shown to substantially reduce cerebral blood flow (CBF) in humans,3, 4 as well as in some animal species,5 these effects may have some relevance to the ventilation-stimulating effect of theophylline. If the acid-base status in the brain is altered as a consequence of changes in CBF, it would affect the activity of the central chemosensitivity and thus the level of ventilation. Since some animal studies have shown that effects of theophylline on CBF are apparent during hypoxia but not during normoxia,6, 7 the effect of theophylline on the PCO2 and acid-base status in the brain may be changeable during normoxia and hypoxia. One approach by which we can approximately estimate what is occurring in the brain in humans is to measure partial gas pressures and pH in the internal jugular vein. With a technique for sampling blood from the internal jugular vein, we have previously shown that PCO2 in the internal jugular vein significantly decreases, by 2 to 3 mmHg, under isocapnic hypoxia,8, 9 which probably reflects hypoxia-induced cerebral vasodilation. The aims of this study are first to evaluate the effect of theophylline on PCO2 and pH in the internal jugular vein for a wide range of arterial PO2 (PaO2) under isocapnic conditions and second to examine the possibility that the augmented ventilatory response to hypoxia caused by theophylline is due to attenuation of hypoxia-induced cerebral vasodilation.

Keywords

Cerebral Blood Flow Internal Jugular Vein Ventilatory Response Severe Hypoxia Adenosine Receptor Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    S. Lakshminarayan, S.A. Sahn, and J.V. Weil, Effect of aminophylline on ventilatory responses in normal man, Am. Rev. Respir. Dis. 117: 33 (1978).PubMedGoogle Scholar
  2. 2.
    EL. Eldridge, D.E. Millhorn, T.G. Waldrop, and J.P. Kiley, Mechanism of respiratory effects of methylxanthines, Respir. Physiol. 53: 239 (1983).PubMedCrossRefGoogle Scholar
  3. 3.
    R.L. Wechsler, L.M. Kleiss, and S.S. Kety, The effects of intravenously administered aminophylline on cerebral circulation and metabolism in man, J. Clin. Invest. 29: 28 (1950).PubMedCrossRefGoogle Scholar
  4. 4.
    U. Gottstein and O.B. Paulson, The effect of intracarotid aminophylline infusion on the cerebral circulation, Stroke 3: 560 (1972).PubMedCrossRefGoogle Scholar
  5. 5.
    S. Morii, A.C. Ngai, K.R. Ko, and H.R. Winn, Role of adenosine in regulation of cerebral blood flow: effects of theophylline during normoxia and hypoxia, Am. J. Physiol. 253: H165 (1987).PubMedGoogle Scholar
  6. 6.
    W.E. Hoffman, R.F. Albrecht, and DJ. Miletich, The role of adenosine in CBF increases during hypoxia in young and aged rats, Stroke 15:124 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    T.E. Emerson Jr and R.M. Raymond, Involvement of adenosine in cerebral hypoxic hyperemia in the dog, Am. J. Physiol. 241: H134 (1981).PubMedGoogle Scholar
  8. 8.
    M. Nishimura, A. Suzuki, Y. Nishiura, H. Yamamoto, K. Miyamoto, F. Kishi, and Y. Kawakami, Effect of brain blood flow on hypoxic ventilatory response in humans, J. Appl. Physiol. 63: 1100 (1987).PubMedGoogle Scholar
  9. 9.
    A. Suzuki, M. Nishimura, H. Yamamoto, K. Miyamoto, F. Kishi, and Y. Kawakami, No effect of brain blood flow on ventilatory depression during sustained hypoxia, J. Appl. Physiol. 66: 1674 (1989).PubMedGoogle Scholar
  10. 10.
    M. Nishimura, A. Suzuki, A. Yoshioka, M. Yamamoto, Y. Akiyama, K. Miyamoto, F. Kishi, and Y. Kawakami, Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive pulmonary disease, Thorax: in print (1992).Google Scholar
  11. 11.
    Y. Kawakami, T. Yoshikawa, Y. Asanuma, and M. Murao, A control system for arterial blood gases, J. Appl. Physiol. 50: 1362 (1981).PubMedGoogle Scholar
  12. 12.
    P.J. Cohen, S.C. Alexander, T.C. Smith, M. Reivich, and H. Wollman, Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man, J. Appl. Physiol. 23: 183 (1967).PubMedGoogle Scholar
  13. 13.
    D.L. Bowton, W.S. Haddon, D.S. Prough, N. Adair, P.T. Alford, and D.A. Stump, Theophylline effect on the cerebral blood flow response to hypoxemia, Chest 94:371 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Javaheri, J.A.M. Evers, and L.J. Teppema, Increase in ventilation caused by aminophylline in the absence of changes in ventral medullary extracellular fluid pH and carbon dioxide tension, Thorax 44: 121 (1989).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Masaharu Nishimura
    • 1
  • Aya Kakinoki
    • 1
  • Shuichi Kobayashi
    • 1
  • Makoto Yamamoto
    • 1
  • Yasushi Akiyama
    • 1
  • Kenji Miyamoto
    • 1
  • Yoshikazu Kawakami
    • 1
  1. 1.First Department of MedicineHokkaido University Scool of MedicineSapporoJapan

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