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.
Similar content being viewed by others
References
Eldridge N. Life on earth: an encyclopedia of biodiversity, ecology, and evolution. Santa Barbara (CA): ABC-CLIO Inc., 2002
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
WHO. World health statistics annual. Geneva: World Health Organization; 1996
West JB. The physiologic basis of high-altitude diseases. Ann Intern Med 2004; 141: 789–800
Lundby C, Robach P, Saltin B. The evolving science of detection of ‘blood doping’. Br J Pharmacol 2012; 165: 1306–15
Ekblom B, Goldbarg AN, Gullbring B. Response to exercise after blood loss and reinfusion. J Appl Physiol 1972; 33: 175–80
Buick FJ, Gledhill N, Froese AB, et al. Effect of induced erythrocythemia on aerobic work capacity. J Appl Physiol 1980; 48: 636–42
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
Turner DL, Hoppeler H, Noti C, et al. Limitations to VO2max in humans after blood retransfusion. Respir Physiol 1993; 92: 329–41
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
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
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
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
Calbet JA, Lundby C, Koskolou M, et al. Importance of hemoglobin concentration to exercise: acute manipulations. Respir Physiol Neurobiol 2006; 151: 132–40
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
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
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
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
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
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
Powers SK, Williams J. Exercise-induced hypoxaemia in highly trained athletes. Sports Med 1987; 4: 46–53
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
Harms CA, McClaran SR, Nickele GA, et al. Exercise-induced arterial hypoxaemia in healthy young women. J Physiol 1998; 507 (Pt 2): 619–28
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
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
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
Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol 1999; 87: 1997–2006
Nielsen HB. Arterial desaturation during exercise in man: implication for O2 uptake and work capacity. Scand J Med Sci Sports 2003; 13: 339–58
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
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
Andersen P, Saltin B. Maximal perfusion of skeletal muscle in man. J Physiol 1985; 366: 233–49
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
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
Fahraeus R. The suspension stability of the blood. Physiol Rev 1929; 9: 241–74
Fåhraeus R, Lindqvist T. The viscosity of the blood in narrow capillary tubes. Am J Physiol 1931; 96: 562–8
Duling BR, Damon DH. An examination of the measurement of flow heterogeneity in striated muscle. Circ Res 1987; 60: 1–13
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
Carr RT, Wickham LL. Influence of vessel diameter on red cell distribution at microvascular bifurcations. Microvasc Res 1991; 41: 184–96
Pries AR, Ley K, Claassen M, et al. Red cell distribution at microvascular bifurcations. Microvasc Res 1989; 38: 81–101
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
Stone HO, Thompson Jr HK, Schmidt-Nielsen K. Influence of erythrocytes on blood viscosity. Am J Physiol 1968; 214: 913–8
Richardson TQaACG. Effects of polycythemia and anemia on cardiac output and other circulatory factors. Am J Physiol 1959; 197: 1167–70
Guyton ACaTQR. Effect of hematocrit on venous return. Circ Res 1961; 9: 157–64
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
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
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
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
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
Harrison MH. Effects on thermal stress and exercise on blood volume in humans. Physiol Rev 1985; 65: 149–209
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
Stewart IB, Warburton DE, Hodges AN, et al. Cardiovascular and splenic responses to exercise in humans. J Appl Physiol 2003; 94: 1619–26
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
Rowell LB. Human cardiovascular control. New York: Oxford University Press; 1993
Schmidt W, Prommer N. Impact of alterations in total hemoglobin mass on VO 2max. Exerc Sport Sci Rev 2010; 38: 68–75
Juvonen E, Ikkala E, Fyhrquist F, et al. Autosomal dominant erythrocytosis caused by increased sensitivity to erythropoietin. Blood 1991; 78: 3066–9
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
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
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
Pugh LG. Blood volume and haemoglobin concentration at altitudes above 18,000 Ft. (5500 M). J Physiol 1964; 170: 344–54
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
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
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
Rahn H, Otis AB. Man’srespiratory response during and after acclimatization to high altitude. Am J Physiol 1949; 157: 445–62
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
Cerny FC, Dempsey JA, Reddan WG. Pulmonary gas exchange in nonnative residents of high altitude. J Clin Invest 1973; 52: 2993–9
Grover RF, Weil JV, Reeves JT. Cardiovascular adaptation to exercise at high altitude. Exerc Sport Sci Rev 1986; 14: 269–302
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
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
Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol 2003; 546: 921–9
Lundby C, Calbet JA, Robach P. The response of human skeletal muscle tissue to hypoxia. Cell Mol Life Sci 2009; 66: 3615–23
Hoppeler H, Vogt M. Muscle tissue adaptations to hypoxia. J Exp Biol 2001; 204: 3133–9
Hoppeler H, Vogt M, Weibel ER, et al. Response of skeletal muscle mitochondria to hypoxia. Exp Physiol 2003; 88: 109–19
Perrey S, Rupp T. Altitude-induced changes in muscle contractile properties. High Alt Med Biol 2009; 10: 175–82
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
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
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
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
Lundby C, Damsgaard R. Exercise performance in hypoxia after novel erythropoiesis stimulating protein treatment. Scand J Med Sci Sports 2006; 16: 35–40
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
Young AJ, Sawka MN, Muza SR, et al. Effects of erythrocyte infusion on VO2max at high altitude. J Appl Physiol 1996; 81: 252–9
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
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
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
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
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
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
Hainsworth R, Drinkhill MJ. Cardiovascular adjustments for life at high altitude. Respir Physiol Neurobiol 2007; 158: 204–11
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
Wenger RH, Gassmann M. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem 1997; 378: 609–16
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
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
Simonson TS, Yang Y, Huff CD, et al. Genetic evidence for high-altitude adaptation in Tibet. Science 2010; 329: 72–5
Yi X, Liang Y, Huerta-Sanchez E, et al. Sequencing of 50 human exomes reveals adaptation to high altitude. Science 2010; 329: 75–8
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
Hakim TS, Macek AS. Effect of hypoxia on erythrocyte deformability in different species. Biorheology 1988; 25: 857–68
Kaniewski WS, Hakim TS, Freedman JC. Cellular deformability of normoxic and hypoxic mammalian red blood cells. Biorheology 1994; 31: 91–101
Hakim TS, Macek AS. Role of erythrocyte deformability in the acute hypoxic pressor response in the pulmonary vasculature. Respir Physiol 1988; 72: 95–107
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
Doyle MP, Walker BR. Stiffened erythrocytes augment the pulmonary hemodynamic response to hypoxia. J Appl Physiol 1990; 69: 1270–5
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
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
Hopfl G, Ogunshola O, Gassmann M. Hypoxia and high altitude: the molecular response. Adv Exp Med Biol 2003; 543: 89–115
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
Fandrey J, Gorr TA, Gassmann M. Regulating cellular oxygen sensing by hydroxylation. Cardiovasc Res 2006; 71: 642–51
Wehrlin JP, Hallen J. Linear decrease in VO2max and performance with increasing altitude in endurance athletes. Eur J Appl Physiol 2006; 96: 404–12
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
Fulco CS, Rock PB, Cymerman A. Maximal and sub-maximal exercise performance at altitude. Aviat Space Environ Med 1998; 69: 793–801
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
Faulkner JA, Daniels JT, Balke B. Effects of training at moderate altitude on physical performance capacity. J Appl Physiol 1967; 23: 85–9
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
Consolazio CF, Nelson RA, Matoush LR, et al. Energy metabolism at high altitude (3,475 m). J Appl Physiol 1966; 21: 1732–40
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
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
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
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
Balke B, Nagle FJ, Daniels J. Altitude and maximum performance in work and sports activity. JAMA 1965; 194: 646–9
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
Pugh LG. Athletes at altitude. J Physiol 1967; 192: 619–46
Bender PR, Groves BM, McCullough RE, et al. Oxygen transport to exercising leg in chronic hypoxia. J Appl Physiol 1988; 65: 2592–7
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
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
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
Levine BD, Stray-Gundersen J, Mehta RD. Effect of altitude on football performance. Scand J Med Sci Sports 2008; 18 Suppl 1: 76–84
Saunders PU, Pyne DB, Gore CJ. Endurance training at altitude. High Alt Med Biol 2009; 10: 135–48
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
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
Bogdanova A, Mihov D, Lutz H, et al. Enhanced erythrophagocytosis in polycythemic mice overexpressing erythropoietin. Blood 2007; 110: 762–9
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
Vogel J, Gassmann M. Erythropoietic and non-erythropoietic functions of erythropoietin in mouse models. J Physiol 2011; 589: 1259–64
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
Gassmann M, Heinicke K, Soliz J, et al. Non-erythroid functions of erythropoietin. Adv Exp Med Biol 2003; 543: 323–30
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
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
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
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
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
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
Wagner PD. Reduced maximal cardiac output at altitude: mechanisms and significance. Respir Physiol 2000; 120: 1–11
Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Prog Cardiovasc Dis 2010; 52: 456–66
Alexander JK, Grover RF. Mechanism of reduced cardiac stroke volume at high altitude. Clin Cardiol 1983; 6: 301–3
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
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
Pugh LG, Gill MB, Lahiri S, et al. Muscular exercise at great altitudes. J Appl Physiol 1964; 19: 431–40
Pugh LGCE. Cardiac output in muscular exercise at 5,800m (19,000 ft). J Appl Physiol 1964; 441–7
Levine BD. VO2max: what do we know, and what do we still need to know? J Physiol 2008; 586: 25–34
Wagner PD. New ideas on limitations to VO2max. Exerc Sport Sci Rev 2000; 28: 10–4
Maher JT, Jones LG, Hartley LH. Effects of high-altitude exposure on submaximal endurance capacity of men. J Appl Physiol 1974; 37: 895–8
Fulco CS, Rock PB, Cymerman A. Improving athletic performance: is altitude residence or altitude training helpful? Aviat Space Environ Med 2000; 71: 162–71
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
Welch HG. Effects of hypoxia and hyperoxia on human performance. Exerc Sport Sci Rev 1987; 15: 191–221
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
West JB, Boyer SJ, Graber DJ, et al. Maximal exercise at extreme altitudes on Mount Everest. J Appl Physiol 1983; 55: 688–98
Wagner PD. A theoretical analysis of factors determining VO2 MAX at sea level and altitude. Respir Physiol 1996; 106: 329–43
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
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
Piiper J. Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle. Acta Physiol Scand 2000; 168: 603–7
Amann M, Calbet JA. Convective oxygen transport and fatigue. J Appl Physiol 2008; 104: 861–70
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
Nielsen HB, Bredmose PP, Stromstad M, et al. Bicarbonate attenuates arterial desaturation during maximal exercise in humans. J Appl Physiol 2002; 93: 724–31
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
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
Brutsaert TD. Do high-altitude natives have enhanced exercise performance at altitude? Appl Physiol Nutr Metab 2008; 33: 582–92
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
Corresponding author
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03262286