European Journal of Applied Physiology

, Volume 93, Issue 1–2, pp 47–56 | Cite as

Control of erythropoiesis after high altitude acclimatization

  • Gustave SavoureyEmail author
  • Jean-Claude Launay
  • Yves Besnard
  • Angélique Guinet
  • Cyprien Bourrilhon
  • Damien Cabane
  • Serge Martin
  • Jean-Pierre Caravel
  • Jean-Marc Péquignot
  • Jean-Marie Cottet-Emard
Original Article


Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) (P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content (CaO2) (+12.93%) at the end of HH (P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (−46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only (r=−0.66, P<0.03). Inverse linear relationships were also found between CaO2 and EPO at the end of HH before (r=−0.63, P<0.05) and after the sojourn (r=−0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.


Erythropoiesis Human High altitude acclimatization Erythropoietin 2,3-diphosphoglycerate 



The subjects of the Mountain Club of the ESSA LYON-BRON are acknowledged, as well as the technical assistance of A. Alonso, A.M. Hanniquet, J. Denis, A. Vouillarmet, R.M. Cottet-Emard and F. Grimbert. A special recognition is given to Médecin général Jacques Bittel.


  1. Böning D, Maassen N, Jochum F, Steinacker J, Halder A, Thomas A, Schmidt W, Noe G, Kubanek B (1997) After-effects of a high altitude expedition on blood. Int J Sports Med 18:179–185PubMedGoogle Scholar
  2. Eckardt KU, Boutellier U, Kurtz A, Schopen M, Koller EA, Bauer C (1989) Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia. J Appl Physiol 66:1785–1788PubMedGoogle Scholar
  3. Eckardt KU, Dittmer J, Neumann R, Bauer C, Kurtz A (1990) Decline of erythropoietin formation at continuous hypoxia is not due to feedback inhibition. Am J Physiol 258 :F1432–F1437PubMedGoogle Scholar
  4. Erslev AJ (1991) Erythropoietin titers in health and disease. Semin Hematol 28 [Suppl 3]:2–7Google Scholar
  5. Erslev AJ, Caro J (1987) Erythropoietin titers in response to anemia or hypoxia. Blood Cells 13:207–216PubMedGoogle Scholar
  6. Fried W, Barone Varelas J (1984) Regulation of the plasma erythropoietin level in hypoxic rats. Exp Hematol 12:706–711PubMedGoogle Scholar
  7. Ge RL, Witkowski S, Zhang Y, Alfrey C, Sivieri M, Karlsen T, Resaland GK, Harber M, Stray Gundersen J, Levine BD (2002) Determinants of erythropoietin release in response to short-term hypobaric hypoxia. J Appl Physiol 92:2361–2367PubMedGoogle Scholar
  8. Gunga HC, Kirsch K, Röcker L, Schobersberger W (1994) Time course of erythropoietin, triiodothyronine, thyroxine, and thyroid-stimulating hormone at 2,315 m. J Appl Physiol 76:1068–1072PubMedGoogle Scholar
  9. Gunga HC, Wittels P, Gunther T, Kanduth B, Vormann J, Röcker L, Kirsch K (1996) Erythropoietin in 29 men during and after prolonged physical stress combined with food and fluid deprivation. Eur J Appl Physiol 73:11–16Google Scholar
  10. Hochachka PW, Gunga HC, Kirsch K (1998) Our ancestral physiological phenotype: an adaptation for hypoxia tolerance and for endurance performance? Proc Natl Acad Sci USA 95:1915–1920CrossRefPubMedGoogle Scholar
  11. Jelkmann W (1992) Erythropoietin: structure, control of production, and function. Physiol Rev 72 (2):449–489PubMedGoogle Scholar
  12. Jelkmann W, Hellwig Burgel T (2001) Biology of erythropoietin. Adv Exp Med Biol 502:169–187PubMedGoogle Scholar
  13. Kayser B (1992) Nutrition and high altitude exposure. Int J Sports Med 13 [Suppl 1]:S129–132Google Scholar
  14. Lenfant C, Sullivan K (1971) Adaptation to high altitude. N Engl J Med 284:1298–1309PubMedGoogle Scholar
  15. Lenfant C, Torrance JD, Reynafarje C (1971) Shift of the O2-Hb dissociation curve at altitude: mechanism and effect. J Appl Physiol 30:625–631PubMedGoogle Scholar
  16. Lohman TG, Boileau RA, Massey BH (1975) Prediction of lean body mass in young boys from skinfold thickness and body weight. Hum Biol 45:245–262Google Scholar
  17. Mairbäurl H, Schobersberger W, Oelz O, Bartsch P, Eckardt KU, Bauer C (1990) Unchanged in vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate. J Appl Physiol 68:1186–1194PubMedGoogle Scholar
  18. Mide SM, Huygens P, Bozzini CE, Fernandez Pol JA (2001) Effects of human recombinant erythropoietin on differentiation and distribution of erythroid progenitor cells on murine medullary and splenic erythropoiesis during hypoxia and post-hypoxia. In Vivo 15:125–132PubMedGoogle Scholar
  19. Milledge JS, Cotes PM (1985) Serum erythropoietin in humans at high altitude and its relation to plasma renin. J Appl Physiol 59:360–364PubMedGoogle Scholar
  20. Richalet JP, Souberbielle JC, Antezana AM, Dechaux M, Le Trong JL, Bienvenu A, Daniel F, Blanchot C, Zittoun J (1994) Control of erythropoiesis in humans during prolonged exposure to the altitude of 6,542 m. Am J Physiol 266 :R756–R764PubMedGoogle Scholar
  21. Savourey G, Garcia N, Besnard Y, Guinet A, Hanniquet AM, Bittel J (1996) Pre-adaptation, adaptation and de-adaptation to high altitude in humans: cardio-ventilatory and haematological changes. Eur J Appl Physiol 73:529–535Google Scholar
  22. Savourey G, Garcia N, Caravel J-P, Gharib C, Pouzeratte N, Martin S, Bittel J (1998) Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level. Eur J Appl Physiol 77:37–43CrossRefGoogle Scholar
  23. Sawka MN, Young AJ, Rock PB, Lyons TP, Boushel R, Freund BJ, Muza SR, Cymerman A, Dennis RC, Pandolf KB, Valeri CR (1996) Altitude acclimatization and blood volume: effects of exogenous erythrocyte volume expansion. J Appl Physiol 81:636–642PubMedGoogle Scholar
  24. Sawka MN, Convertino VA, Eichner ER, Schnieder SM, Young AJ (2000) Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness. Med Sci Sports Exerc 32:332–348CrossRefPubMedGoogle Scholar
  25. Semenza GL (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88 (4):1474–1480PubMedGoogle Scholar
  26. Ward MP, Milledge JS, West JB (1995) High altitude medicine and physiology, 2nd edn. Chapman and Hall, London, p 497Google Scholar
  27. Zhu H, Jackson T, Bunn HF (2002) Detecting and responding to hypoxia. Nephrol Dial Transplant 17 [Suppl 1]:3–7Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Gustave Savourey
    • 1
    Email author
  • Jean-Claude Launay
    • 1
  • Yves Besnard
    • 1
  • Angélique Guinet
    • 1
  • Cyprien Bourrilhon
    • 2
  • Damien Cabane
    • 1
  • Serge Martin
    • 1
  • Jean-Pierre Caravel
    • 3
  • Jean-Marc Péquignot
    • 4
  • Jean-Marie Cottet-Emard
    • 5
  1. 1.Centre de recherches du service de santé des armées38702, La Tronche cedexFrance
  2. 2.Institut de médecine aéronautique du service de santé des armées 91223, Brétigny sur Orge cedexFrance
  3. 3.Service de médecine nucléaire, Hôpital MichallonCHU Grenoble38043, Grenoble cedex 9France
  4. 4.UMR CNRS 5123Université Claude Bernard–Lyon IVilleurbanne CedexFrance
  5. 5.Laboratoire de physiologie de l’environnementFaculté de médecine Grange Blanche69373, Lyon cedex 08France

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