Mixed Venous CO2 and Ventilation During Exercise and CO2-Rebreathing in Humans

  • Toru Satoh
  • Yasumasa Okada
  • Yasushi Hara
  • Fumio Sakamaki
  • Shingo Kyotani
  • Takeshi Tomita
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 551)


The physiological mechanism of exercise-induced hyperpnea is an important and long-standing issue in respiratory physiology research.1 However, the precise mechanism of exercise-induced hyperpnea still is not understood. It has been confirmed that neural central command from the hypothalamus plays an important role in respiratory control during exercise.2 Activation of receptors in working muscle3,4 and stimulation of the carotid body by elevated plasma potassium5 have both been shown to contribute to exercise-induced hyperpnea. However, most of the other hypotheses to explain exercise-induced hyperpnea have been based on the observed close relationship between ventilation and the level of metabolic work; these hypotheses include (1) sensing of CO2 by receptors in the pulmonary circulation,6, 7, 8, 9 (2) sensing of arterial CO2 partial pressure (PaCO2) as well as PaCO2 oscillation by the carotid body10,11 and (3) modulation of stretch-sensitive afferent activity by CO2.12,13 Thus, it has been widely assumed that metabolically produced CO2 is the most important element in the mechanism of exercise-induced hyperpnea. Therefore, the relationship between ventilation (Ve) and mixed venous CO2 partial pressure (PvCO2) as well as the relationship between Ve and PaCO2 needs to be fully analyzed in order to understand the contribution of metabolically produced CO2 to exercise-induced hyperpnea. However, most of the previous reports on PvCO2 dynamics during exercise in humans were not based on direct measurement, but rather on the estimation of PvCO2 by CO2 rebreathing,14,l5 and PvCO2 has been directly measured during exercise in humans only in a few studies.16 This is mainly because sampling of mixed venous blood during exercise in humans is technically difficult.


Carotid Body Ventilatory Response Respiratory Control Mixed Venous Blood Central Chemoreceptor 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. H. Mateika, and J. Duffin, A review of the control of breathing during exercise, Eur. J. Appl. Physiol. 71, 1–27 (1995).CrossRefGoogle Scholar
  2. 2.
    F. L. Eldridge, D. E. Millhom, and T. G. Waldrop, Exercise hyperpnea and locomotion: parallel activation from the hypothalamus, Science, 211, 844–846 (1981).CrossRefPubMedGoogle Scholar
  3. 3.
    H. V. Forster, and L. G. Pan, Contribution of acid-base changes to control of breathing during exercise, Can. J. Appl. Physiol. 20, 380–394 (1995).PubMedGoogle Scholar
  4. 4.
    D. A. Oelberg, A. B. Evans, M. I. Hrovat, P. P. Pappagianopoulos, S. Patz, and D. M. Systrom, Skeletal muscle chemoreflex and pHi in exercise ventilatory control, J. Appl. Physiol. 84, 676–682 (1998).PubMedGoogle Scholar
  5. 5.
    D. J. Paterson, P. A. Robbins, and J. Conway, Changes in arterial plasma potassium and ventilation during exercise in man, Respir. Physiol. 78, 323–330 (1989).CrossRefPubMedGoogle Scholar
  6. 6.
    K. R. Kollmeyer, and L. I. Kleinman, A respiratory venous chemoreceptor in the young puppy, J. Appl. Physiol. 38, 819–826 (1975).PubMedGoogle Scholar
  7. 7.
    E. A. Phillipson, G. Bowes, E. R. Townsend, J. Duffin, and J. D. Cooper, Role of metabolic CO2 production in ventilatory response to steady-state exercise, J. Clin. Invest. 68, 768–774 (1981).CrossRefPubMedGoogle Scholar
  8. 8.
    M. I. Sheldon, and J. F. Green, Evidence for pulmonary CO2 chemosensitivity: effects on ventilation. J. Appl. Physiol.: Respir. Environ. Exerc. Physiol. 52, 1192–1197 (1982).Google Scholar
  9. 9.
    E. R. Schertel, D. A. Schneider, L. Adams, and J. F. Green, Effect of pulmonary arterial Pco2 on breathing pattern, J. Appl. Physiol. 64, 1844–1850 (1988).PubMedGoogle Scholar
  10. 10.
    B. A. Cross, A. Davey, A. Guz, P. G. Katona, M. MacLean, K. Murphy, S. J. G. Semple, and R. P. Stidwell, The pH oscillations in arterial blood during exercise: a potential signal for the ventilatory response in the dog, J. Physiol. (Lond.) 329, 57–73 (1982).Google Scholar
  11. 11.
    S. A. Ward, Peripheral and central chemoreceptor control of ventilation during exercise in humans, Can. J. Appl. Physiol. 19, 305–333 (1994).PubMedGoogle Scholar
  12. 12.
    J. F. Green, E. R. Schertel, H. M. Coleridge, and J. C. Coleridge, Effect of pulmonary arterial Pco2 on slowly adapting pulmonary stretch receptors, J. Appl. Physiol. 60, 2048–2055 (1986).PubMedGoogle Scholar
  13. 13.
    E. S. Schelegle, and J. F. Green, An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors, Respir. Physiol. 125, 17–31 (2001).CrossRefPubMedGoogle Scholar
  14. 14.
    J. H. Auchincloss, R. Gilbert, M. Kuppinger, and D. Peppi, Mixed venous CO2 tension during exercise, J. Appl. Physiol.: Respir. Environ. Exerc. Physiol. 48, 933–938 (1980).Google Scholar
  15. 15.
    G. Alves da Silva, A. el-Manshawi, G. J. Heigenhauser, and N. L. Jones, Measurement of mixed venous carbon dioxide pressure by rebreathing during exercise, Respir. Physiol. 59, 379–392 (1985).CrossRefPubMedGoogle Scholar
  16. 16.
    R. Casaburi, J. Daly, J. E. Hansen, and R. M. Effros, Abrupt changes in mixed venous blood gas composition after the onset of exercise, J. Appl. Physiol. 67, 1106–1112 (1989).PubMedGoogle Scholar
  17. 17.
    B. F Whipp, and K. Wasserman, Carotid bodies and ventilatory control dynamics in man. Fed. Proc. 39, 2668–2673 (1980).PubMedGoogle Scholar
  18. 18.
    Y. Okada, Z. Chen, and S. Kuwana S, Cytoarchitecture of central chemoreceptors in the mammalian ventral medulla. Respir. Physiol. 291, 13–23 (2001).CrossRefGoogle Scholar
  19. 19.
    G. J. A. Cropp, and J. H. J. Comroe, Role of mixed venous blood Pco2 in respiratory control. J. Appl. Physiol. 16, 1029–1033 (1961).PubMedGoogle Scholar
  20. 20.
    J. T. Sylvester, B. J. Whipp, and K. Wasserman, Ventilatory control during brief infusions of CO2-laden blood in the awake dog. J. Appl. Physiol. 35, 178–186 (1973).PubMedGoogle Scholar
  21. 21.
    J. A. Orr, M. R. Fedde, H. Shams, H. Roskenbleck, and P. Scheid, Absence of CO2-sensitive venous chemoreceptors in the cat. Respir. Physiol. 73, 211–224 (1988).CrossRefPubMedGoogle Scholar
  22. 22.
    Y. Okada, T. Satoh, S. Kuwana, M. Kashiwagi, and T. Kusakabe, Electrical stimulation of the rabbit pulmonary artery increases respiratory output, Respir. Physiol. Neurobiol. 140, 209–217 (2004).CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2004

Authors and Affiliations

  • Toru Satoh
    • 1
    • 3
  • Yasumasa Okada
    • 2
  • Yasushi Hara
    • 1
  • Fumio Sakamaki
    • 1
  • Shingo Kyotani
    • 1
  • Takeshi Tomita
    • 1
  1. 1.Department of MedicineKeio University Shool of MedicineTokyoJapan
  2. 2.Division of Cardiology and Pulmonary Circulation, Department of MedicineNational Cardiovascular CenterSuita, OsakaJapan
  3. 3.Department of MedicineKeio University Tsukigase Rehabilitation CenterShizuokaJapan

Personalised recommendations