Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

  • E. Magosso
  • M. Ursino
Special Section: Modelling and simulation in biomedicine


The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO2) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O2 extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO2 of approximately 45 mmHg.


Cardiovascular regulation Blood flow redistribution High altitude Oxygen venous concentration Oxygen consumption 


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  1. Abboud, F. M., andThames, M. D. (1983): ‘Interaction of cardiovascular reflexes in circulatory control’ inShepherd, J. T., Abboud, F. M., andGeiger, S. R. (Eds): ‘Handbook of physiology, section. II, vol. III, The cardiovascular system: peripheral circulation and organ blood flow’, (American Physiological Society, Bethesda, Maryland, 1983), pp. 675–753Google Scholar
  2. Case, R. B., Felix, A., Wachter, M., Kyriakidis, G., andCastellana, F. (1978): ‘Relative effect of CO2 on canine coronary vascular resistance’,Circ. Res.,42, pp. 410–418Google Scholar
  3. Cunningham, D. J. C., Robbins, P. A., andWolff, C. B. (1986): ‘Integration of respiratory responses to changes in alveolar partial pressures of CO2 and O2 and in arterial pH’, inFishman, A. P., Cherniack, N. S., Widdicombe, J. G., andGeiger, S. R. (Eds): ‘Handbook of physiology, section 3: Respiratory system, vol. 2, Control of breathing, Part 2’ (American Physiological Society, Bethesda, MD, 1986), pp. 475–528Google Scholar
  4. Daly, M. B., Hazzledine, J. L., andUngar, A. (1967): ‘The reflex effect of alterations in lung volume on systemic vascular resistance in the dog’,J. Physiol.,188, pp. 331–351Google Scholar
  5. Daugherty, R. M. J., Scott, G. B., Dabney, J. M., andHaddy, F. J. (1967): ‘Local effects of O2 and CO2 on limb, renal, and coronary vascular resistances’,Am. J. Physiol.,213, pp. 1102–1110Google Scholar
  6. Downing, S. E., Mitchell, J. H., andWallace, A. G. (1963): ‘Cardiovascular responses to ischemia, hypoxia and hypercapnia of the central nervous system’,Am. J. Physiol.,204, pp. 881–887Google Scholar
  7. Edvinsson, L., Mackenzie, E. T., andMcculloch, J. (1992): ‘Cerebral blood flow and metabolism’ (Raven Press, New York, 1992)Google Scholar
  8. Fitzgerald, R. S., andParks, D. C. (1971): ‘Effect of hypoxia on carotid chemoreceptor response to carbon dioxide in cats’,Respir. Physiol.,12, pp. 218–229CrossRefGoogle Scholar
  9. Guyton, A. C., Coleman, T. G., andGranger, H. J. (1972): ‘Circulation: overall regulation’,Ann. Rev. Physiol.,34, pp. 13–46Google Scholar
  10. Heistad, D. D., andAbboud, F. M. (1980): ‘Circulatory adjustments to hypoxia’,Circulation,61, pp. 463–470Google Scholar
  11. Hutter, J., Habler, O., Kleen, M., Tiede, M., Podtschaske, A., Kemming, G., Corso, C., Batra, S., Keipert, P., Faithfull, S., andMessmer, K. (1999): ‘Effect of acute normovolemic hemodilution on distribution of blood flow and tissue oxygenation in dog skeletal muscle’,J. Appl. Physiol.,86, pp. 860–866Google Scholar
  12. Lahiri, S., andDelaney, R. G. (1975): ‘Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers’,Respir. Physiol.,24, pp. 249–266Google Scholar
  13. Levy, M. N., andShare, L. (1953): ‘Influence of erythrocyte concentration upon the pressure-flow relationships in the dog’s hind limb’,Circ. Res.,1, pp. 247–255Google Scholar
  14. Magosso, E., andUrsino, M. (2001): ‘A mathematical model of CO2 effect on cardiovascular regulation’,Am. J. Physiol. Heart Circ. Physiol.,281, pp. H2036-H2052Google Scholar
  15. Magosso, E., andUrsino, M. (2002): ‘Cardiovascular response to dynamic aerobic exercise: a mathematical model’,Med. Biol. Eng. Comput.,40, pp. 660–674CrossRefGoogle Scholar
  16. McPiierson, R. W., Eimerl, D., andTraystman, R. J. (1987): ‘Interaction of hypoxia and hypercapnia on cerebral hemodynamics and brain electrical activity in dogs’,Am. J. Physiol.,253, pp. H890-H897 (Heart Circ. Physiol.,22)Google Scholar
  17. Metivier, F., Marchais, S. J., Guerin, A. P., Pannier, B., andLondon, G. M. (2000): ‘Pathophysiology of anaemia: focus on the heart and blood vessels’,Nephrol. Dial. Transplant.,15, pp. 14–18Google Scholar
  18. Mines, A. H. (1993): ‘Respiratory physiology’ (Raven Press, New York, 1993)Google Scholar
  19. Murray, J. F., Escobar, E., andRapaport, E. (1969): ‘Effects of blood viscosity on hemodynamic responses in acute normovolemic anemia’,Am. J. Physiol.,216, pp. 638–642Google Scholar
  20. Pavek, K., andCarey, J. S. (1974): ‘Hemodynamics and oxygen availability during isovolemic hemodilution’,Am. J. Physiol.,226, pp. 1172–1177Google Scholar
  21. Radawski, D., Dabney, J. M., Daugherty, R. M. J., Haddy, F. J., andScott, J. B. (1972): ‘Local effects of CO2 on vascular resistances and weight of the dog forelimb’,Am. J. Physiol.,222, pp. 439–443Google Scholar
  22. Riley, R. L. (1971): ‘Scambio e trasporto dei gas’, inRuch, T. C., andPatton, H. D. (Eds): ‘Fisiologia e Biofisica di J.F. Fulton — W.H. Howell’ (Società Editrice Universo, Roma, 1971), pp. 1135–1172Google Scholar
  23. Spencer, J. L., Firouztale, E., andMellins, R. B. (1979): ‘Computational expressions for blood oxygen and carbon dioxide concentrations’,Ann. Biomed. Eng.,7, pp. 59–66Google Scholar
  24. Stowe, D. F., Owen, T. L., Anderson, D. K., Haddy, F. J., andScott, J. B. (1975): ‘Interaction of O2 and CO2 in sustained exercise hyperemia of canine skeletal muscle’,Am. J. Physiol.,229, pp. 28–33Google Scholar
  25. Ter Minassian, A., Beyond, L., Ursino, M., Gardette, B., Gortan, C., andRichalet, J. P. (2001): ‘Doppler study of middle cerebral artery blood flow velocity and cerebral autoregulation during a simulated ascent of Mount Everest’,Wilderness Environ. Med.,12, pp. 175–183Google Scholar
  26. Thews, G. (1967): ‘Gaseous diffusion in the lungs and tissues’, inReeve, E. B., andGuyton, A. C. (Eds): ‘Physical bases of circulatory transport: regulation and exchange’ (Saunders, Philadelphia, 1967), pp. 327–341Google Scholar
  27. Ursino, M. (1998): ‘Interaction between carotid baroregulation and the pulsating heart: a mathematical model’,Am. J. Physiol.,275, pp. H1733-H1747 (Heart Circ. Physiol.,44)Google Scholar
  28. Ursino, M., andMagosso, E. (2000a): ‘Acute cardiovascular response to isocapnic hypoxia. I: a mathematical model’,Am. J. Physiol. Heart Circ. Physiol.,279, pp. H149-H165Google Scholar
  29. Ursino, M., andMagosso, E. (2000b): ‘Acute cardiovascular response to isocapnic hypoxia. II: model validation’,Am. J. Physiol. Heart Circ. Physiol.,279, pp. H166-H175Google Scholar
  30. Varat, M. A., Adolph, R. J., andFowler, N. O. (1972): ‘Cardiovascular effects of anemia’,Am. Heart J.,83, pp. 415–426CrossRefGoogle Scholar
  31. Vatner, S. F., Higgins, C. B., andFranklin, D. (1972): ‘Regional circulatory adjustments to moderate and severe chronic anemia in conscious dogs at rest and during exercise’,Circ. Res.,30, pp. 731–740Google Scholar
  32. Whittaker, S. R. F., andWinton, F. R. (1933): ‘Apparent viscosity of blood flowing in the isolated hind limb of the dog, and its variation with corpuscoler concentration’,J. Physiol. (Lond),78, pp. 339–369Google Scholar

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© IFMBE 2004

Authors and Affiliations

  1. 1.Department of Electronics, Computer Science & SystemsUniversity of BolognaBolognaItaly

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