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Kinetics of Changes in Hemoglobin After Ascent to and Return from High Altitude

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Abstract

Decreased oxygen availability in sojourners requires adjustments in tissue oxygen supply, the most effective of which is an increase in the hemoglobin (Hb) concentration. It is achieved by two independent processes: a fast increase in Hb is achieved by decreasing plasma volume due to enhanced renal Na- and water excretion. A further but slow increase in Hb concentration is achieved by stimulation of erythropoiesis by mechanisms depending on stabilization of hypoxia-inducible factor 2α resulting in elevated levels of erythropoietin in blood. The magnitude of decrease in plasma volume and of stimulation of erythropoiesis depends on the degree and duration of exposure to hypoxia at high altitude. Upon descent from high to low altitude elevated O2-transport capacity is no longer needed. Thus, plasma volume can be restored and excess erythrocytes can be removed from circulation. This latter process is called erythrolysis. Its effectiveness seems to depend on the altitude to which individuals had been exposed. Whereas most of the excess erythrocytes seem to be removed from circulation within 1–2 weeks after a stay at altitudes > 3500 m, total Hb mass seems to remain elevated for up to 4 weeks when individuals had been exposed to more moderate altitudes, e.g. in the range of 2500 m. These are the altitudes where athletes typically perform altitude training. Thus, it appears that improved performance in the weeks after return from altitude training depends in part on maintaining elevated total Hb mass, which is known to increase aerobic capacity.

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References

  1. Alfrey CP, Rice L, Udden MM, Driscoll TB. Neocytolysis: physiological down-regulator of red-cell mass. Lancet. 1997;349(9062):1389–90. https://doi.org/10.1016/S0140-6736(96)09208-2(PubMed PMID: 9149714).

    Article  CAS  PubMed  Google Scholar 

  2. Bärtsch P, Swenson ER. Clinical practice: acute high-altitude illnesses. N Engl J Med. 2013;368(24):2294–302. https://doi.org/10.1056/NEJMcp1214870(PubMed PMID: 23758234).

    Article  CAS  PubMed  Google Scholar 

  3. Bärtsch P, Swenson ER, Paul A, Julg B, Hohenhaus E. Hypoxic ventilatory response, ventilation, gas exchange, and fluid balance in acute mountain sickness. High Altit Med Biol. 2002;3(4):361–76. https://doi.org/10.1089/15270290260512846PubMed PMID: 12631422.

    Article  Google Scholar 

  4. Beall CM. Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integr Comp Biol. 2006;46(1):18–24.

    Article  Google Scholar 

  5. Berlin NI, Reynafarje C, Lawrence JH. Red cell life span in the polycythemia of high altitude. J Appl Physiol. 1954;7(3):271–2.

    Article  CAS  Google Scholar 

  6. Bouverot P. Adaptation to altitude hypoxia in vertebrates. Berlin: Springer Verlag; 1985.

    Book  Google Scholar 

  7. Brutsaert TD. Do high-altitude natives have enhanced exercise performance at altitude? Appl Physiol Nutr Metab. 2008;33(3):582–92. https://doi.org/10.1139/h08-009(Epub 2008/05/08. PubMed PMID: 18461115).

    Article  CAS  PubMed  Google Scholar 

  8. Calbet JA, Boushel R, Radegran G, Sondergaard H, Wagner PD, Saltin B. Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content? Am J Physiol. 2003;284(2):R304–16. https://doi.org/10.1152/ajpregu.00156.2002.

    Article  CAS  Google Scholar 

  9. Chapman RF, StrayGundersen J, Levine BD. Individual variation in response to altitude training. J Appl Physiol. 1998;85(4):1448–56.

    Article  CAS  Google Scholar 

  10. Chapman RF, Laymon Stickford AS, Lundby C, Levine BD. Timing of return from altitude training for optimal sea level performance. J Appl Physiol. 2014;116(7):837–43. https://doi.org/10.1152/japplphysiol.00663.2013PubMed PMID: 24336885.

    Article  PubMed  Google Scholar 

  11. Christensen RD, Lambert DK, Henry E, Yaish HM, Prchal JT. End-tidal carbon monoxide as an indicator of the hemolytic rate. Blood Cells Mol Dis. 2015;54(3):292–6. https://doi.org/10.1016/j.bcmd.2014.11.018(PubMed PMID: 25624169).

    Article  CAS  PubMed  Google Scholar 

  12. Cremona G, Asnaghi P, Baderna P, Brunetto A, Brutsaert T, Cavallaro C, Clark TM, Cogo A, Donis R, Lanfranchi P, Luks A, Novello N, Panzetta S, Perini L, Putnam M, Spagnolatti L, Wagner H, Wagner PD. Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study. Lancet. 2002;359(9303):303–9.

    Article  Google Scholar 

  13. Dempsey JA, Reddan WG, Birnbaum ML, Forster HV, Thoden JS, Grover RF, Rankin J. Effects of acute through life-long hypoxic exposure on exercise pulmonary gas exchange. Respir Physiol. 1971;13(1):62–89 Epub 1971/10/01 PubMed PMID: 5112830.

    Article  CAS  Google Scholar 

  14. Faulkner JA, Daniels JT, Balke B. Effects of training at moderate altitude on physical performance capacity. J Appl Physiol. 1967;23(1):85–9.

    Article  CAS  Google Scholar 

  15. Fryers GR, Berlin NI. Mean red cell life of rats exposed to reduced barometric pressure. Am J Physiol. 1952;171(2):465–70 Epub 1952/11/01 PubMed PMID: 13007817.

    Article  CAS  Google Scholar 

  16. Garvican L, Martin D, Quod M, Stephens B, Sassi A, Gore C. Time course of the hemoglobin mass response to natural altitude training in elite endurance cyclists. Scand J Med Sci Sports. 2012;22(1):95–103. https://doi.org/10.1111/j.1600-0838.2010.01145.x(Epub 2010/06/22. PubMed PMID: 20561279).

    Article  CAS  PubMed  Google Scholar 

  17. Garvican-Lewis LA, Sharpe K, Gore CJ. Time for a new metric for hypoxic dose? J Appl Physiol. 2016;121(1):352–5. https://doi.org/10.1152/japplphysiol.00579.2015(Epub 2016/02/27. PubMed PMID: 26917695).

    Article  PubMed  Google Scholar 

  18. Gassmann M, Muckenthaler MU. Adaptation of iron requirement to hypoxic conditions at high altitude. J Appl Physiol. 2015;119(12):1432–40. https://doi.org/10.1152/japplphysiol.00248.2015(PubMed PMID: 26183475).

    Article  CAS  PubMed  Google Scholar 

  19. Hannon JP, Vogel JA. Oxygen transport during early altitude acclimatization: a perspectiv study. Eur J Appl Physiol Occup Physiol. 1977;36(4):285–97.

    Article  CAS  Google Scholar 

  20. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010;142(1):24–38.

    Article  CAS  Google Scholar 

  21. Hohenhaus E, Paul A, McCullough RE, Kücherer H, Bärtsch P. Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema. Eur Respir J. 1995;8(11):1825–33.

    Article  CAS  Google Scholar 

  22. Huff RL, Lawrence JH, Siri WE, Wasserman LR, Hennessy TG. Effects of changes in altitude on hematopoietic activity. Medicine (Baltimore). 1951;30(3):197–217 PubMed PMID: 14881989.

    Article  CAS  Google Scholar 

  23. Kjellberg SR, Rudhe U, Sjostrand T. Increase of the amount of hemoglobin and blood volume in connection with physical training. Acta Physiol Scand. 1949;19(2–3):146–52.

    Article  Google Scholar 

  24. Klausen K, Dill DB, Horvath SM. Exercise at ambient and high oxygen pressure at high altitude and at sea level. J Appl Physiol. 1970;29(4):456–63. https://doi.org/10.1152/jappl.1970.29.4.456(Epub 1970/10/01. PubMed PMID: 5459913).

    Article  CAS  PubMed  Google Scholar 

  25. Landaw SA. Factors that accelerate or retard red blood cell senescence. Blood Cells. 1988;14(1):47–59.

    CAS  PubMed  Google Scholar 

  26. Levine BD, Stray-Gundersen J. “Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol. 1997;83(1):102–12.

    Article  CAS  Google Scholar 

  27. Lundby C, Millet GP, Calbet JA, Bärtsch P, Subudhi AW. Does ‘altitude training’ increase exercise performance in elite athletes? Br J Sports Med. 2012;46(11):792–5.

    Article  Google Scholar 

  28. Mairbäurl H. Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells. Front Physiol. 2013. https://doi.org/10.3389/fphys.2013.00332.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mairbäurl H, Weber RE. Oxygen transport by hemoglobin. Compr Physiol. 2012;2(2):1463–89.

    PubMed  Google Scholar 

  30. Mairbäurl H, Schobersberger W, Oelz O, Bärtsch P, Eckardt KU, Bauer C. Unchanged in vivo P 50 at high altitude despite decreased red cell age and elevated 2,3-DPG. J Appl Physiol. 1990;68(3):1186–94.

    Article  Google Scholar 

  31. Merino CF. Studies on blood formation and destruction in the polycythemia of high altitude. Blood. 1950;5(1):1–31 PubMed PMID: 15396777.

    Article  CAS  Google Scholar 

  32. Milledge JS. Renin-Aldosterone System. In: West JB, Lahiri S, editors. High altitude and man. Bethesda: Williams & Wilkins; 1984. p. 47–57.

    Chapter  Google Scholar 

  33. Milledge JS. Salt and water control at altitude. Int J Sports Med. 1992;13(Suppl 1):S61–3.

    Article  Google Scholar 

  34. Milledge JS, Bryson EI, Catley DM, Hesp R, Luff N, Minty BD, Older MW, Payne NN, Ward MP, Withey WR. Sodium balance, fluid homeostasis and the renin-aldosterone system during the prolonged exercise of hill walking. Clin Sci (Lond). 1982;62(6):595–604.

    Article  CAS  Google Scholar 

  35. Ohi H, Tamano M, Sudo S, Okada N. Recombinant EPO therapy increases erythrocyte expression of complement regulatory proteins. Am J Kidney Dis. 2003;41(1):179–85. https://doi.org/10.1053/ajkd.2003.50002(Epub 2002/12/25. PubMed PMID: 12500235).

    Article  CAS  PubMed  Google Scholar 

  36. Olsen NV. Ventilation, hypocapnia and hypoxia: Effects on renal function. In: Houston CS, Coates G, editors. Hypoxia: women at high altitude. Burlington: Queen City Printers; 1997. p. 284–99.

    Google Scholar 

  37. Olsen NV, Hansen JM, Kanstrup IL, Leyssac OO. Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans. J Appl Physiol. 1993;74(5):2166–73.

    Article  CAS  Google Scholar 

  38. Pace N, Meyer LB, Vaughan BE. Erythrolysis on return of altitude acclimatized individuals to sea level. J Appl Physiol. 1956;9(2):141–4 PubMed PMID: 13376417.

    Article  CAS  Google Scholar 

  39. Prommer N, Thoma S, Quecke L, Gutekunst T, Volzke C, Wachsmuth N, Niess AM, Schmidt W. Total hemoglobin mass and blood volume of elite Kenyan runners. Med Sci Sports Exerc. 2010;42(4):791–7. https://doi.org/10.1249/mss.0b013e3181badd67(Epub 2009/12/03. PubMed PMID: 19952848).

    Article  CAS  PubMed  Google Scholar 

  40. Rasmussen P, Siebenmann C, Diaz V, Lundby C. Red cell volume expansion at altitude: a meta-analysis and Monte Carlo simulation. Med Sci Sports Exerc. 2013;45(9):1767–72. https://doi.org/10.1249/MSS.0b013e31829047e5PubMed PMID: 23502972.

    Article  PubMed  Google Scholar 

  41. Reynafarje C, Lozano R, Valdivieso J. The polycythemia of high altitudes: iron metabolism and related aspects. Blood. 1959;14(4):433–55.

    Article  CAS  Google Scholar 

  42. Rice L, Ruiz W, Driscoll T, Whitley CE, Tapia R, Hachey DL, Gonzales GF, Alfrey CP. Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass. Ann Intern Med. 2001;134(8):652–6 PubMed PMID: 11304105.

    Article  CAS  Google Scholar 

  43. Rifkind RA. Destruction of injured red cells in vivo. Am J Med. 1966;41(5):711–23 (Epub 1966/11/01 PubMed PMID: 5332170).

    Article  CAS  Google Scholar 

  44. Risso A, Turello M, Biffoni F, Antonutto G. Red blood cell senescence and neocytolysis in humans after high altitude acclimatization. Blood Cells Mol Dis. 2007;38(2):83–92. https://doi.org/10.1016/j.bcmd.2006.10.161(PubMed PMID: 17188915).

    Article  CAS  PubMed  Google Scholar 

  45. Risso A, Ciana A, Achilli C, Antonutto G, Minetti G. Neocytolysis: none, one or many? A reappraisal and future perspectives. Front Physiol. 2014;5:54. https://doi.org/10.3389/fphys.2014.00054(PubMed PMID: 24592241; PubMed Central PMCID: PMCPMC3924315).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Rodriguez FA, Iglesias X, Feriche B, Calderon-Soto C, Chaverri D, Wachsmuth NB, Schmidt W, Levine BD. Altitude training in elite swimmers for sea level performance (Altitude Project). Med Sci Sports Exerc. 2015;47(9):1965–78. https://doi.org/10.1249/mss.0000000000000626(Epub 2015/01/30. PubMed PMID: 25628173).

    Article  PubMed  Google Scholar 

  47. Rogers SC, Said A, Corcuera D, McLaughlin D, Kell P, Doctor A. Hypoxia limits antioxidant capacity in red blood cells by altering glycolytic pathway dominance. FASEB J. 2009;23(9):3159–70. https://doi.org/10.1096/fj.09-130666(PubMed PMID: 19417084; PubMed Central PMCID: PMCPMC2735367).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rusko HK, Tikkanen HO, Peltonen JE. Altitude and endurance training. J Sports Sci. 2004;22(10):928–44.

    Article  Google Scholar 

  49. Sawka MN, Convertino VA, Eichner ER, Schnieder SM, Young AJ. Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness. Med Sci Sports Exerc. 2000;32(2):332–48.

    Article  CAS  Google Scholar 

  50. Schmidt W, Prommer N. Impact of alterations in total hemoglobin mass on VO2max. Exerc Sport Sci Rev. 2010;38(2):68–75.

    Article  Google Scholar 

  51. Siebenmann C, Cathomen A, Hug M, Keiser S, Lundby AK, Hilty MP, Goetze JP, Rasmussen P, Lundby C. Hemoglobin mass and intravascular volume kinetics during and after exposure to 3454-m altitude. J Appl Physiol. 2015;119(10):1194–201. https://doi.org/10.1152/japplphysiol.01121.2014(PubMed PMID: 25749449).

    Article  CAS  PubMed  Google Scholar 

  52. Siebenmann C, Robach P, Lundby C. Regulation of blood volume in lowlanders exposed to high altitude. J Appl Physiol. 2017;123(4):957–66. https://doi.org/10.1152/japplphysiol.00118.2017(Epub 2017/06/03. PubMed PMID: 28572493).

    Article  PubMed  Google Scholar 

  53. Song J, Sundar K, Gangaraju R, Prchal JT. Regulation of erythropoiesis after normoxic return from chronic sustained and intermittent hypoxia. J Appl Physiol. 2017;123(6):1671–5. https://doi.org/10.1152/japplphysiol.00119.2017(Epub 2017/05/20. PubMed PMID: 28522758).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Stray-Gundersen J, Levine BD. Live high, train low at natural altitude. Scand J Med Sci Sports. 2008;18(Suppl 1):21–8.

    Article  Google Scholar 

  55. Sutton JR. Exercise training at high altitude: does it improve endurance performance at sea level? Gatorade Sports Sci Inst. 1993;6:45–58.

    Google Scholar 

  56. Swenson ER, Bärtsch P. High-altitude pulmonary edema. Compr Physiol. 2012;2(4):2753–73. https://doi.org/10.1002/cphy.c100029(PubMed PMID: 23720264).

    Article  PubMed  Google Scholar 

  57. Swenson ER, Maggiorini M, Mongovin S, Gibbs JSR, Greve I, Mairbäurl H, Bärtsch P. Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor. J Am Med A. 2002;287(17):2228–35.

    Article  Google Scholar 

  58. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012;92(1):367–520.

    Article  CAS  Google Scholar 

  59. Trial J, Rice L, Alfrey CP. Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: an in vitro model of neocytolysis. J Investig Med. 2001;49(4):335–45. https://doi.org/10.2310/6650.2001.33899(PubMed PMID: 11478410).

    Article  CAS  PubMed  Google Scholar 

  60. Viault F. Sur la quantite d’oxygene contenue dans la sang des animoux des hauts plateaux de l’Amerique du Sud. CRH Acad Sci Paris. 1891;112:295.

    Google Scholar 

  61. Wachsmuth NB, Volzke C, Prommer N, Schmidt-Trucksass A, Frese F, Spahl O, Eastwood A, Stray-Gundersen J, Schmidt W. The effects of classic altitude training on hemoglobin mass in swimmers. Eur J Appl Physiol. 2013;113(5):1199–211. https://doi.org/10.1007/s00421-012-2536-0(Epub 2012/11/10. PubMed PMID: 23138148).

    Article  CAS  PubMed  Google Scholar 

  62. Wachsmuth N, Kley M, Spielvogel H, Aughey RJ, Gore CJ, Bourdon PC, Hammond K, Sargent C, Roach GD, Sanchez RS, Claros JC, Schmidt WF, Garvican-Lewis LA. Changes in blood gas transport of altitude native soccer players near sea-level and sea-level native soccer players at altitude (ISA3600). Br J Sports Med. 2013;47(Suppl 1):i93–9. https://doi.org/10.1136/bjsports-2013-092761(Epub 2014/01/15. PubMed PMID: 24282216; PubMed Central PMCID: PMCPMC3903154).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Weil JV, Byrne-Quinn E, Sodal IE, Friesen WO, Underhill B, Filley GF, Grover RF. Hypoxic ventilatory drive in normal man. J Clin Invest. 1970;49(6):1061–72. https://doi.org/10.1172/JCI106322(PubMed PMID: 5422012; PubMed Central PMCID: PMCPMC322574).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wenger RH, Kurtz A. Erythropoietin. Compr Physiol. 2011;1(4):1759–94. https://doi.org/10.1002/cphy.c100075(Epub 2011/10/01. PubMed PMID: 23733688).

    Article  PubMed  Google Scholar 

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  1. Translational Pneumology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Heimo Mairbäurl

  2. Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany

    Heimo Mairbäurl

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Mairbäurl, H. Kinetics of Changes in Hemoglobin After Ascent to and Return from High Altitude. J. of SCI. IN SPORT AND EXERCISE 2, 7–14 (2020). https://doi.org/10.1007/s42978-019-00044-2

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