Skip to main content
Log in

Red Blood Cell Volume and the Capacity for Exercise at Moderate to High Altitude

  • Review Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Hypoxia-stimulated erythropoiesis, such as that observed when red blood cell volume (RCV) increases in response to high-altitude exposure, is well understood while the physiological importance is not. Maximal exercise tests are often performed in hypoxic conditions following some form of RCV manipulation in an attempt to elucidate oxygen transport limitations at moderate to high altitudes. Such attempts, however, have not made clear the extent to which RCV is of benefit to exercise at such elevations. Changes in RCV at sea level clearly have a direct influence on maximal exercise capacity. Nonetheless, at elevations above 3000m, the evidence is not that clear. Certain studies demonstrate either a direct benefit or decrement to exercise capacity in response to an increase or decrease, respectively, in RCV whereas other studies report negligible effects of RCV manipulation on exercise capacity. Adding to the uncertainty regarding the importance of RCV at high altitude is the observation that Andean and Tibetan high-altitude natives exhibit similar exercise capacities at high altitude (3900m) even though Andean natives often present with a higher percent haematocrit (Hct) when compared with both lowland natives and Tibetans. The current review summarizes past literature that has examined the effect of RCV changes on maximal exercise capacity at moderate to high altitudes, and discusses the explanation elucidating these seemingly paradoxical observations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Table I
Fig. 2
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Eldridge N. Life on earth: an encyclopedia of biodiversity, ecology, and evolution. Santa Barbara (CA): ABC-CLIO Inc., 2002

    Google Scholar 

  2. Moore LG, Niermeyer S, Zamudio S. Human adaptation to high altitude: regional and life-cycle perspectives. Am J Phys Anthropol 1998; Suppl. 27: 25–64

    Article  PubMed  Google Scholar 

  3. WHO. World health statistics annual. Geneva: World Health Organization; 1996

    Google Scholar 

  4. West JB. The physiologic basis of high-altitude diseases. Ann Intern Med 2004; 141: 789–800

    Article  PubMed  Google Scholar 

  5. Lundby C, Robach P, Saltin B. The evolving science of detection of ‘blood doping’. Br J Pharmacol 2012; 165: 1306–15

    Article  PubMed  CAS  Google Scholar 

  6. Ekblom B, Goldbarg AN, Gullbring B. Response to exercise after blood loss and reinfusion. J Appl Physiol 1972; 33: 175–80

    PubMed  CAS  Google Scholar 

  7. Buick FJ, Gledhill N, Froese AB, et al. Effect of induced erythrocythemia on aerobic work capacity. J Appl Physiol 1980; 48: 636–42

    PubMed  CAS  Google Scholar 

  8. Spriet LL, Gledhill N, Froese AB, et al. Effect of graded erythrocythemia on cardiovascular and metabolic responses to exercise. J Appl Physiol 1986; 61: 1942–8

    PubMed  CAS  Google Scholar 

  9. Turner DL, Hoppeler H, Noti C, et al. Limitations to VO2max in humans after blood retransfusion. Respir Physiol 1993; 92: 329–41

    Article  PubMed  CAS  Google Scholar 

  10. Lundby C, Robach P, Boushel R, et al. Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport? J Appl Physiol 2008; 105: 581–7

    Article  PubMed  CAS  Google Scholar 

  11. Thomsen JJ, Rentsch RL, Robach P, et al. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity. Eur J Appl Physiol 2007; 101: 481–6

    Article  PubMed  CAS  Google Scholar 

  12. Robertson RJ, Gilcher R, Metz KF, et al. Hemoglobin concentration and aerobic work capacity in women following induced erythrocythemia. J Appl Physiol 1984; 57: 568–75

    PubMed  CAS  Google Scholar 

  13. Williams MH, Wesseldine S, Somma T, et al. The effect of induced erythrocythemia upon 5-mile treadmill run time. Med Sci Sports Exerc 1981; 13: 169–75

    PubMed  CAS  Google Scholar 

  14. Calbet JA, Lundby C, Koskolou M, et al. Importance of hemoglobin concentration to exercise: acute manipulations. Respir Physiol Neurobiol 2006; 151: 132–40

    Article  PubMed  CAS  Google Scholar 

  15. Roach RC, Koskolou MD, Calbet JA, et al. Arterial O2 content and tension in regulation of cardiac output and leg blood flow during exercise in humans. Am J Physiol 1999; 276: H438–45

    PubMed  CAS  Google Scholar 

  16. Robach P, Calbet JA, Thomsen JJ, et al. The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia. PLoS One 2008; 3 (8): e2996

    Article  PubMed  CAS  Google Scholar 

  17. Ekblom B, Wilson G, Astrand PO. Central circulation during exercise after venesection and reinfusion of red blood cells. J Appl Physiol 1976; 40: 379–83

    PubMed  CAS  Google Scholar 

  18. Nielsen HB, Madsen P, Svendsen LB, et al. The influence of PaO2, pH and SaO2 on maximal oxygen uptake. Acta Physiol Scand 1998; 164: 89–7

    Article  PubMed  CAS  Google Scholar 

  19. Ekblom B, Huot R, Stein EM, et al. Effect of changes in arterial oxygen content on circulation and physical performance. J Appl Physiol 1975; 39: 71–5

    PubMed  CAS  Google Scholar 

  20. Calbet JA, Radegran G, Boushel R, et al. Effect of blood haemoglobin concentration on V(O2, max) and cardiovascular function in lowlanders acclimatised to 5260 m. J Physiol 2002; 545: 715–28

    Article  PubMed  CAS  Google Scholar 

  21. Powers SK, Williams J. Exercise-induced hypoxaemia in highly trained athletes. Sports Med 1987; 4: 46–53

    Article  PubMed  CAS  Google Scholar 

  22. Rice AJ, Scroop GC, Gore CJ, et al. Exercise-induced hypoxaemia in highly trained cyclists at 40% peak oxygen uptake. Eur J Appl Physiol Occup Physiol 1999; 79: 353–9

    Article  PubMed  CAS  Google Scholar 

  23. Harms CA, McClaran SR, Nickele GA, et al. Exercise-induced arterial hypoxaemia in healthy young women. J Physiol 1998; 507 (Pt 2): 619–28

    Article  PubMed  CAS  Google Scholar 

  24. Gale GE, Torre-Bueno JR, Moon RE, et al. Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude. J Appl Physiol 1985; 58: 978–88

    PubMed  CAS  Google Scholar 

  25. Hammond MD, Gale GE, Kapitan KS, et al. Pulmonary gas exchange in humans during exercise at sea level. J Appl Physiol 1986; 60: 1590–8

    PubMed  CAS  Google Scholar 

  26. Wagner PD, Gale GE, Moon RE, et al. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 1986; 61: 260–70

    PubMed  CAS  Google Scholar 

  27. Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol 1999; 87: 1997–2006

    PubMed  CAS  Google Scholar 

  28. Nielsen HB. Arterial desaturation during exercise in man: implication for O2 uptake and work capacity. Scand J Med Sci Sports 2003; 13: 339–58

    Article  PubMed  Google Scholar 

  29. Powers SK, Dodd S, Lawler J, et al. Incidence of exercise induced hypoxemia in elite endurance athletes at sea level. Eur J Appl Physiol Occup Physiol 1988; 58: 298–302

    Article  PubMed  CAS  Google Scholar 

  30. Chapman RF, Emery M, Stager JM. Degree of arterial desaturation in normoxia influences VO2max decline in mild hypoxia. Med Sci Sports Exerc 1999; 31: 658–63

    Article  PubMed  CAS  Google Scholar 

  31. Andersen P, Saltin B. Maximal perfusion of skeletal muscle in man. J Physiol 1985; 366: 233–49

    PubMed  CAS  Google Scholar 

  32. Wagner PD. Counterpoint: in health and in normoxic environment VO2max is limited primarily by cardiac output and locomotor muscle blood flow. J Appl Physiol 2006; 100: 745–7; discussion 7–8

    Article  PubMed  Google Scholar 

  33. Saltin B, Calbet JA. Point: in health and in a normoxic environment, VO2 max is limited primarily by cardiac output and locomotor muscle blood flow. J Appl Physiol 2006; 100: 744–5

    Article  PubMed  Google Scholar 

  34. Fahraeus R. The suspension stability of the blood. Physiol Rev 1929; 9: 241–74

    Google Scholar 

  35. Fåhraeus R, Lindqvist T. The viscosity of the blood in narrow capillary tubes. Am J Physiol 1931; 96: 562–8

    Google Scholar 

  36. Duling BR, Damon DH. An examination of the measurement of flow heterogeneity in striated muscle. Circ Res 1987; 60: 1–13

    Article  PubMed  CAS  Google Scholar 

  37. Krogh A. Studies on the physiology of capillaries: II. The reactions to local stimuli of the blood-vessels in the skin and web of the frog. J Physiol 1921; 55: 412–22

    PubMed  CAS  Google Scholar 

  38. Carr RT, Wickham LL. Influence of vessel diameter on red cell distribution at microvascular bifurcations. Microvasc Res 1991; 41: 184–96

    Article  PubMed  CAS  Google Scholar 

  39. Pries AR, Ley K, Claassen M, et al. Red cell distribution at microvascular bifurcations. Microvasc Res 1989; 38: 81–101

    Article  PubMed  CAS  Google Scholar 

  40. Robertson RJ, Gilcher R, Metz KF, et al. Effect of simulated altitude erythrocythemia in women on hemoglobin flow rate during exercise. J Appl Physiol 1988; 64: 1644–9

    PubMed  CAS  Google Scholar 

  41. Stone HO, Thompson Jr HK, Schmidt-Nielsen K. Influence of erythrocytes on blood viscosity. Am J Physiol 1968; 214: 913–8

    PubMed  CAS  Google Scholar 

  42. Richardson TQaACG. Effects of polycythemia and anemia on cardiac output and other circulatory factors. Am J Physiol 1959; 197: 1167–70

    Google Scholar 

  43. Guyton ACaTQR. Effect of hematocrit on venous return. Circ Res 1961; 9: 157–64

    Article  PubMed  CAS  Google Scholar 

  44. Schuler B, Arras M, Keller S, et al. Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice. Proc Natl Acad Sci U S A 2010; 107: 419–23

    Article  PubMed  CAS  Google Scholar 

  45. Villafuerte FC, Cardenas R, Monge CC. Optimal hemoglobin concentration and high altitude: a theoretical approach for Andean men at rest. J Appl Physiol 2004; 96: 1581–8

    Article  PubMed  CAS  Google Scholar 

  46. Pace N, Consolazio WV, Lozner EL. The effect of transfusions of red blood cells on the hypoxia tolerance of normal men. Science 1945; 102: 589–91

    Article  PubMed  CAS  Google Scholar 

  47. Robertson RJ, Gilcher R, Metz KF, et al. Effect of induced erythrocythemia on hypoxia tolerance during physical exercise. J Appl Physiol 1982; 53: 490–5

    Article  PubMed  CAS  Google Scholar 

  48. Crowell JW, Ford RG, Lewis VM. Oxygen transport in hemorrhagic shock as a function of the hematocrit ratio. Am J Physiol 1959; 196: 1033–8

    PubMed  CAS  Google Scholar 

  49. Harrison MH. Effects on thermal stress and exercise on blood volume in humans. Physiol Rev 1985; 65: 149–209

    PubMed  CAS  Google Scholar 

  50. Laub M, Hvid-Jacobsen K, Hovind P, et al. Spleen emptying and venous hematocrit in humans during exercise. J Appl Physiol 1993; 74: 1024–6

    PubMed  CAS  Google Scholar 

  51. Stewart IB, Warburton DE, Hodges AN, et al. Cardiovascular and splenic responses to exercise in humans. J Appl Physiol 2003; 94: 1619–26

    PubMed  Google Scholar 

  52. Hsia CC, Johnson Jr RL, Dane DM, et al. The canine spleen in oxygen transport: gas exchange and hemodynamic responses to splenectomy. J Appl Physiol 2007; 103: 1496–505

    Article  PubMed  CAS  Google Scholar 

  53. Rowell LB. Human cardiovascular control. New York: Oxford University Press; 1993

    Google Scholar 

  54. Schmidt W, Prommer N. Impact of alterations in total hemoglobin mass on VO 2max. Exerc Sport Sci Rev 2010; 38: 68–75

    Article  PubMed  Google Scholar 

  55. Juvonen E, Ikkala E, Fyhrquist F, et al. Autosomal dominant erythrocytosis caused by increased sensitivity to erythropoietin. Blood 1991; 78: 3066–9

    PubMed  CAS  Google Scholar 

  56. Winslow RM, Monge CC, Brown EG, et al. Effects of hemodilution on O2 transport in high-altitude polycythemia. J Appl Physiol 1985; 59: 1495–502

    PubMed  CAS  Google Scholar 

  57. Horstman D, Weiskopf R, Jackson RE. Work capacity during 3-wk sojourn at 4,300 m: effects of relative polycythemia. J Appl Physiol 1980; 49: 311–8

    PubMed  CAS  Google Scholar 

  58. Tufts DA, Haas JD, Beard JL, et al. Distribution of hemoglobin and functional consequences of anemia in adult males at high altitude. Am J Clin Nutr 1985; 42: 1–11

    PubMed  CAS  Google Scholar 

  59. Pugh LG. Blood volume and haemoglobin concentration at altitudes above 18,000 Ft. (5500 M). J Physiol 1964; 170: 344–54

    PubMed  CAS  Google Scholar 

  60. 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: 102–12

    PubMed  CAS  Google Scholar 

  61. Forster HV, Dempsey JA, Birnbaum ML, et al. Effect of chronic exposure to hypoxia on ventilatory response to CO 2 and hypoxia. J Appl Physiol 1971; 31: 586–92

    PubMed  CAS  Google Scholar 

  62. Lundby C, Calbet JA, van Hall G, et al. Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives. Am J Physiol Regul Integr Comp Physiol 2004; 287: R1202–8

    Article  PubMed  CAS  Google Scholar 

  63. Rahn H, Otis AB. Man’srespiratory response during and after acclimatization to high altitude. Am J Physiol 1949; 157: 445–62

    PubMed  CAS  Google Scholar 

  64. Dempsey JA, Forster HV, Birnbaum ML, et al. Control of exercise hyperpnea under varying durations of exposure to moderate hypoxia. Respir Physiol 1972; 16: 213–31

    Article  PubMed  CAS  Google Scholar 

  65. Cerny FC, Dempsey JA, Reddan WG. Pulmonary gas exchange in nonnative residents of high altitude. J Clin Invest 1973; 52: 2993–9

    Article  PubMed  CAS  Google Scholar 

  66. Grover RF, Weil JV, Reeves JT. Cardiovascular adaptation to exercise at high altitude. Exerc Sport Sci Rev 1986; 14: 269–302

    Article  PubMed  CAS  Google Scholar 

  67. Reeves JT, Mazzeo RS, Wolfel EE, et al. Increased arterial pressure after acclimatization to 4300 m: possible role of norepinephrine. Int J Sports Med 1992; 13 Suppl. 1: 18–21

    Article  Google Scholar 

  68. Boushel R, Calbet JA, Radegran G, et al. Parasympathetic neural activity accounts for the lowering of exercise heart rate at high altitude. Circulation 2001; 104: 1785–91

    Article  PubMed  CAS  Google Scholar 

  69. Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol 2003; 546: 921–9

    Article  PubMed  CAS  Google Scholar 

  70. Lundby C, Calbet JA, Robach P. The response of human skeletal muscle tissue to hypoxia. Cell Mol Life Sci 2009; 66: 3615–23

    Article  PubMed  CAS  Google Scholar 

  71. Hoppeler H, Vogt M. Muscle tissue adaptations to hypoxia. J Exp Biol 2001; 204: 3133–9

    PubMed  CAS  Google Scholar 

  72. Hoppeler H, Vogt M, Weibel ER, et al. Response of skeletal muscle mitochondria to hypoxia. Exp Physiol 2003; 88: 109–19

    Article  PubMed  CAS  Google Scholar 

  73. Perrey S, Rupp T. Altitude-induced changes in muscle contractile properties. High Alt Med Biol 2009; 10: 175–82

    Article  PubMed  CAS  Google Scholar 

  74. Mizuno M, Juel C, Bro-Rasmussen T, et al. Limb skeletal muscle adaptation in athletes after training at altitude. J Appl Physiol 1990; 68: 496–502

    PubMed  CAS  Google Scholar 

  75. Lundby C, Pilegaard H, van Hall G, et al. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia. Toxicology 2003; 192: 229–36

    Article  PubMed  CAS  Google Scholar 

  76. Barnholt KE, Hoffman AR, Rock PB, et al. Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction. Am J Physiol Endocrinol Metab 2006; 290: E1078–88

    Article  PubMed  CAS  Google Scholar 

  77. Roberts AC, Butterfield GE, Cymerman A, et al. Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate. J Appl Physiol 1996; 81: 1762–71

    PubMed  CAS  Google Scholar 

  78. Lundby C, Damsgaard R. Exercise performance in hypoxia after novel erythropoiesis stimulating protein treatment. Scand J Med Sci Sports 2006; 16: 35–40

    Article  PubMed  CAS  Google Scholar 

  79. Schaffartzik W, Barton ED, Poole DC, et al. Effect of reduced hemoglobin concentration on leg oxygen uptake during maximal exercise in humans. J Appl Physiol 1993; 75: 491–8; discussion 89–90

    PubMed  CAS  Google Scholar 

  80. Young AJ, Sawka MN, Muza SR, et al. Effects of erythrocyte infusion on VO2max at high altitude. J Appl Physiol 1996; 81: 252–9

    PubMed  CAS  Google Scholar 

  81. Pandolf KB, Young AJ, Sawka MN, et al. Does erythrocyte infusion improve 3.2-km run performance at high altitude? Eur J Appl Physiol Occup Physiol 1998; 79: 1–6

    Article  PubMed  CAS  Google Scholar 

  82. Schuler B, Thomsen JJ, Gassmann M, et al. Timing the arrival at 2340 m altitude for aerobic performance. Scand J Med Sci Sports 2007; 17: 588–94

    Article  PubMed  CAS  Google Scholar 

  83. Calbet JA, Boushel R, Radegran G, et al. Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content? Am J Physiol Regul Integr Comp Physiol 2003; 284: R304–16

    PubMed  CAS  Google Scholar 

  84. Reynafarje C, Faura J, Paredes A, et al. Erythrokinetics in high-altitude-adapted animals (llama, alpaca, and vicuna). J Appl Physiol 1968; 24: 93–7

    PubMed  CAS  Google Scholar 

  85. Beall CM, Brittenham GM, Strohl KP, et al. Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara. Am J Phy Anthrop 1998; 106: 385–400

    Article  CAS  Google Scholar 

  86. Beall CM, Decker MJ, Brittenham GM, et al. An Ethiopian pattern of human adaptation to high-altitude hypoxia. Proc Natl Acad Sci U S A 2002; 99: 17215–8

    Article  PubMed  CAS  Google Scholar 

  87. Hainsworth R, Drinkhill MJ. Cardiovascular adjustments for life at high altitude. Respir Physiol Neurobiol 2007; 158: 204–11

    Article  PubMed  Google Scholar 

  88. Favier R, Spielvogel H, Desplanches D, et al. Maximal exercise performance in chronic hypoxia and acute normoxia in high-altitude natives. J Appl Physiol 1995; 78: 1868–74

    PubMed  CAS  Google Scholar 

  89. Wenger RH, Gassmann M. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem 1997; 378: 609–16

    PubMed  CAS  Google Scholar 

  90. Tissot van Patot MC, Gassmann M. Hypoxia: adapting to high altitude by mutating EPAS-1, the gene encoding HIF-2alpha. High Alt Med Biol 2011; 12: 157–67

    Article  CAS  Google Scholar 

  91. Beall CM, Cavalleri GL, Deng L, et al. Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A 2010; 107: 11459–64

    Article  PubMed  CAS  Google Scholar 

  92. Simonson TS, Yang Y, Huff CD, et al. Genetic evidence for high-altitude adaptation in Tibet. Science 2010; 329: 72–5

    Article  PubMed  CAS  Google Scholar 

  93. Yi X, Liang Y, Huerta-Sanchez E, et al. Sequencing of 50 human exomes reveals adaptation to high altitude. Science 2010; 329: 75–8

    Article  PubMed  CAS  Google Scholar 

  94. Beall CM. Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc Natl Acad Sci U S A 2007; 104 Suppl. 1: 8655–60

    Article  PubMed  CAS  Google Scholar 

  95. Hakim TS, Macek AS. Effect of hypoxia on erythrocyte deformability in different species. Biorheology 1988; 25: 857–68

    PubMed  CAS  Google Scholar 

  96. Kaniewski WS, Hakim TS, Freedman JC. Cellular deformability of normoxic and hypoxic mammalian red blood cells. Biorheology 1994; 31: 91–101

    PubMed  CAS  Google Scholar 

  97. Hakim TS, Macek AS. Role of erythrocyte deformability in the acute hypoxic pressor response in the pulmonary vasculature. Respir Physiol 1988; 72: 95–107

    Article  PubMed  CAS  Google Scholar 

  98. Hill NS, Sardella GL, Ou LC. Reticulocytosis, increased mean red cell volume, and greater blood viscosity in altitude susceptible compared to altitude resistant rats. Respir Physiol 1987; 70: 229–40

    PubMed  CAS  Google Scholar 

  99. Doyle MP, Walker BR. Stiffened erythrocytes augment the pulmonary hemodynamic response to hypoxia. J Appl Physiol 1990; 69: 1270–5

    PubMed  CAS  Google Scholar 

  100. Reinhart WH, Kayser B, Singh A, et al. Blood rheology in acute mountain sickness and high-altitude pulmonary edema. J Appl Physiol 1991; 71: 934–8

    PubMed  CAS  Google Scholar 

  101. Palareti G, Coccheri S, Poggi M, et al. Changes in the rheologic properties of blood after a high altitude expedition. Angiology 1984; 35: 451–8

    Article  PubMed  CAS  Google Scholar 

  102. Hopfl G, Ogunshola O, Gassmann M. Hypoxia and high altitude: the molecular response. Adv Exp Med Biol 2003; 543: 89–115

    Article  PubMed  Google Scholar 

  103. Fandrey J, Gassmann M. Oxygen sensing and the activation of the hypoxia inducible factor 1 (HIF-1)- invited article. Adv Exp Med Biol 2009; 648: 197–206

    Article  PubMed  CAS  Google Scholar 

  104. Fandrey J, Gorr TA, Gassmann M. Regulating cellular oxygen sensing by hydroxylation. Cardiovasc Res 2006; 71: 642–51

    Article  PubMed  CAS  Google Scholar 

  105. Wehrlin JP, Hallen J. Linear decrease in VO2max and performance with increasing altitude in endurance athletes. Eur J Appl Physiol 2006; 96: 404–12

    Article  PubMed  Google Scholar 

  106. Buskirk ER, Kollias J, Akers RF, et al. Maximal performance at altitude and on return from altitude in conditioned runners. J Appl Physiol 1967; 23: 259–66

    PubMed  CAS  Google Scholar 

  107. Fulco CS, Rock PB, Cymerman A. Maximal and sub-maximal exercise performance at altitude. Aviat Space Environ Med 1998; 69: 793–801

    PubMed  CAS  Google Scholar 

  108. Adams WC, Bernauer EM, Dill DB, et al. Effects of equivalent sea-level and altitude training on VO2max and running performance. J Appl Physiol 1975; 39: 262–6

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  110. 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: 456–63

    PubMed  CAS  Google Scholar 

  111. Consolazio CF, Nelson RA, Matoush LR, et al. Energy metabolism at high altitude (3,475 m). J Appl Physiol 1966; 21: 1732–40

    PubMed  CAS  Google Scholar 

  112. Lundby C, Van Hall G. Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m. Acta Physiol Scand 2002; 176: 195–201

    Article  PubMed  CAS  Google Scholar 

  113. Lundby C, Sander M, van Hall G, et al. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J Physiol 2006; 573: 535–47

    Article  PubMed  CAS  Google Scholar 

  114. Wolfel EE, Groves BM, Brooks GA, et al. Oxygen transport during steady-state submaximal exercise in chronic hypoxia. J Appl Physiol 1991; 70: 1129–36

    PubMed  CAS  Google Scholar 

  115. Hansen JE, Vogel JA, Stelter GP, et al. Oxygen uptake in man during exhaustive work at sea level and high altitude. J Appl Physiol 1967; 23: 511–22

    PubMed  CAS  Google Scholar 

  116. Balke B, Nagle FJ, Daniels J. Altitude and maximum performance in work and sports activity. JAMA 1965; 194: 646–9

    Article  PubMed  CAS  Google Scholar 

  117. Calbet JA, Radegran G, Boushel R, et al. Plasma volume expansion does not increase maximal cardiac output or VO2 max in lowlanders acclimatized to altitude. Am J Physiol Heart Circ Physiol 2004; 287: H1214–24

    Article  PubMed  CAS  Google Scholar 

  118. Pugh LG. Athletes at altitude. J Physiol 1967; 192: 619–46

    PubMed  CAS  Google Scholar 

  119. Bender PR, Groves BM, McCullough RE, et al. Oxygen transport to exercising leg in chronic hypoxia. J Appl Physiol 1988; 65: 2592–7

    PubMed  CAS  Google Scholar 

  120. Boutellier U, Deriaz O, di Prampero PE, et al. Aerobic performance at altitude: effects of acclimatization and hematocrit with reference to training. Int J Sports Med 1990; 11 Suppl. 1:21–6

    Article  Google Scholar 

  121. Grassi B, Marzorati M, Kayser B, et al. Peak blood lactate and blood lactate vs. workload during acclimatization to 5,050m and in deacclimatization. J Appl Physiol 1996; 80: 685–92

    PubMed  CAS  Google Scholar 

  122. Prommer N, Heinicke K, Viola T, et al. Long-term intermittent hypoxia increases O2-transport capacity but not VO2max. High Alt Med Biol 2007; 8: 225–35

    Article  PubMed  Google Scholar 

  123. Levine BD, Stray-Gundersen J, Mehta RD. Effect of altitude on football performance. Scand J Med Sci Sports 2008; 18 Suppl 1: 76–84

    Article  PubMed  Google Scholar 

  124. Saunders PU, Pyne DB, Gore CJ. Endurance training at altitude. High Alt Med Biol 2009; 10: 135–48

    Article  PubMed  Google Scholar 

  125. Hochachka PW, Gunga HC, Kirsch K. Our ancestral physiological phenotype: an adaptation for hypoxia tolerance and for endurance performance? Proc Natl Acad Sci U S A 1998; 95: 1915–20

    Article  PubMed  CAS  Google Scholar 

  126. Vogel J, Kiessling I, Heinicke K, et al. Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity. Blood 2003; 102: 2278–84

    Article  PubMed  CAS  Google Scholar 

  127. Bogdanova A, Mihov D, Lutz H, et al. Enhanced erythrophagocytosis in polycythemic mice overexpressing erythropoietin. Blood 2007; 110: 762–9

    Article  PubMed  CAS  Google Scholar 

  128. Ruschitzka FT, Wenger RH, Stallmach T, et al. Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proc Natl Acad Sci U S A 2000; 97: 11609–13

    Article  PubMed  CAS  Google Scholar 

  129. Vogel J, Gassmann M. Erythropoietic and non-erythropoietic functions of erythropoietin in mouse models. J Physiol 2011; 589: 1259–64

    Article  PubMed  CAS  Google Scholar 

  130. Salazar Vazquez BY, Martini J, Chavez Negrete A, et al. Microvascular benefits of increasing plasma viscosity and maintaining blood viscosity: counterintuitive experimental findings. Biorheology 2009; 46: 167–79

    PubMed  CAS  Google Scholar 

  131. Gassmann M, Heinicke K, Soliz J, et al. Non-erythroid functions of erythropoietin. Adv Exp Med Biol 2003; 543: 323–30

    Article  PubMed  CAS  Google Scholar 

  132. Rasmussen P, Foged EM, Krogh-Madsen R, et al. Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men. J Appl Physiol 2010; 109: 476–83

    Article  PubMed  CAS  Google Scholar 

  133. Krzywicki HJ, Consolazio CF, Johnson HL, et al. Water metabolism in humans during acute high-altitude exposure (4,300 m). J Appl Physiol 1971; 30: 806–9

    PubMed  CAS  Google Scholar 

  134. Alexander JK, Hartley LH, Modelski M, et al. Reduction of stroke volume during exercise in man following ascent to 3,100m altitude. J Appl Physiol 1967; 23: 849–58

    PubMed  CAS  Google Scholar 

  135. Sawka MN, Young AJ, Rock PB, et al. Altitude acclimatization and blood volume: effects of exogenous erythrocyte volume expansion. J Appl Physiol 1996; 81: 636–42

    PubMed  CAS  Google Scholar 

  136. Robach P, Lafforgue E, Olsen NV, et al. Recovery of plasma volume after 1 week of exposure at 4,350 m. Pflugers Arch 2002; 444: 821–8

    Article  PubMed  CAS  Google Scholar 

  137. Robach P, Dechaux M, Jarrot S, et al. Operation Everest III: role of plasma volume expansion on VO(2)(max) during prolonged high-altitude exposure. J Appl Physiol 2000; 89: 29–37

    PubMed  CAS  Google Scholar 

  138. Wagner PD. Reduced maximal cardiac output at altitude: mechanisms and significance. Respir Physiol 2000; 120: 1–11

    Article  PubMed  CAS  Google Scholar 

  139. Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Prog Cardiovasc Dis 2010; 52: 456–66

    Article  PubMed  Google Scholar 

  140. Alexander JK, Grover RF. Mechanism of reduced cardiac stroke volume at high altitude. Clin Cardiol 1983; 6: 301–3

    Article  PubMed  CAS  Google Scholar 

  141. Suarez J, Alexander JK, Houston CS. Enhanced left ventricular systolic performance at high altitude during Operation Everest II. Am J Cardiol 1987; 60: 137–42

    Article  PubMed  CAS  Google Scholar 

  142. Grover RF, Reeves JT, Maher JT, et al. Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2. Circ Res 1976; 38: 391–6

    Article  PubMed  CAS  Google Scholar 

  143. Pugh LG, Gill MB, Lahiri S, et al. Muscular exercise at great altitudes. J Appl Physiol 1964; 19: 431–40

    PubMed  CAS  Google Scholar 

  144. Pugh LGCE. Cardiac output in muscular exercise at 5,800m (19,000 ft). J Appl Physiol 1964; 441–7

  145. Levine BD. VO2max: what do we know, and what do we still need to know? J Physiol 2008; 586: 25–34

    Article  PubMed  CAS  Google Scholar 

  146. Wagner PD. New ideas on limitations to VO2max. Exerc Sport Sci Rev 2000; 28: 10–4

    PubMed  CAS  Google Scholar 

  147. Maher JT, Jones LG, Hartley LH. Effects of high-altitude exposure on submaximal endurance capacity of men. J Appl Physiol 1974; 37: 895–8

    PubMed  CAS  Google Scholar 

  148. Fulco CS, Rock PB, Cymerman A. Improving athletic performance: is altitude residence or altitude training helpful? Aviat Space Environ Med 2000; 71: 162–71

    PubMed  CAS  Google Scholar 

  149. Winslow RM, Monge CC, Statham NJ, et al. Variability of oxygen affinity of blood: human subjects native to high altitude. J Appl Physiol 1981; 51: 1411–6

    PubMed  CAS  Google Scholar 

  150. Welch HG. Effects of hypoxia and hyperoxia on human performance. Exerc Sport Sci Rev 1987; 15: 191–221

    Article  PubMed  CAS  Google Scholar 

  151. Amann M, Romer LM, Subudhi AW, et al. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 2007; 581: 389–403

    Article  PubMed  CAS  Google Scholar 

  152. West JB, Boyer SJ, Graber DJ, et al. Maximal exercise at extreme altitudes on Mount Everest. J Appl Physiol 1983; 55: 688–98

    PubMed  CAS  Google Scholar 

  153. Wagner PD. A theoretical analysis of factors determining VO2 MAX at sea level and altitude. Respir Physiol 1996; 106: 329–43

    Article  PubMed  CAS  Google Scholar 

  154. Calbet JA, Boushel R, Radegran G, et al. Determinants of maximal oxygen uptake in severe acute hypoxia. Am J Physiol Regul Integr Comp Physiol 2003; 284: R291–303

    PubMed  CAS  Google Scholar 

  155. Torre-Bueno JR, Wagner PD, Saltzman HA, et al. Diffusion limitation in normal humans during exercise at sea level and simulated altitude. J Appl Physiol 1985; 58: 989–95

    PubMed  CAS  Google Scholar 

  156. Piiper J. Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle. Acta Physiol Scand 2000; 168: 603–7

    Article  PubMed  CAS  Google Scholar 

  157. Amann M, Calbet JA. Convective oxygen transport and fatigue. J Appl Physiol 2008; 104: 861–70

    Article  PubMed  Google Scholar 

  158. Jacobs RA, Rasmussen P, Siebenmann C, et al. Determinants of time trial performance and maximal incremental exercise in highly trained endurance athletes. J Appl Physiol 2011; 111: 1422–30

    Article  PubMed  CAS  Google Scholar 

  159. Nielsen HB, Bredmose PP, Stromstad M, et al. Bicarbonate attenuates arterial desaturation during maximal exercise in humans. J Appl Physiol 2002; 93: 724–31

    PubMed  Google Scholar 

  160. Calbet JA, Radegran G, Boushel R, et al. On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass. J Physiol 2009; 587: 477–90

    Article  PubMed  CAS  Google Scholar 

  161. Dempsey JA, Reddan WG, Birnbaum ML, et al. Effects of acute through life-long hypoxic exposure on exercise pulmonary gas exchange. Respir Physiol 1971; 13: 62–89

    Article  PubMed  CAS  Google Scholar 

  162. Brutsaert TD. Do high-altitude natives have enhanced exercise performance at altitude? Appl Physiol Nutr Metab 2008; 33: 582–92

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No funding was received to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert A. Jacobs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jacobs, R.A., Lundby, C., Robach, P. et al. Red Blood Cell Volume and the Capacity for Exercise at Moderate to High Altitude. Sports Med 42, 643–663 (2012). https://doi.org/10.1007/BF03262286

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03262286

Keywords

Navigation