Semin Respir Crit Care Med 2023; 44(05): 681-695
DOI: 10.1055/s-0043-1770063
Review Article

High Altitude

1   Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
,
Andrew M. Luks
2   Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, Washington
› Institutsangaben

Abstract

With ascent to high altitude, barometric pressure declines, leading to a reduction in the partial pressure of oxygen at every point along the oxygen transport chain from the ambient air to tissue mitochondria. This leads, in turn, to a series of changes over varying time frames across multiple organ systems that serve to maintain tissue oxygen delivery at levels sufficient to prevent acute altitude illness and preserve cognitive and locomotor function. This review focuses primarily on the physiological adjustments and acclimatization processes that occur in the lungs of healthy individuals, including alterations in control of breathing, ventilation, gas exchange, lung mechanics and dynamics, and pulmonary vascular physiology. Because other organ systems, including the cardiovascular, hematologic and renal systems, contribute to acclimatization, the responses seen in these systems, as well as changes in common activities such as sleep and exercise, are also addressed. While the pattern of the responses highlighted in this review are similar across individuals, the magnitude of such responses often demonstrates significant interindividual variability which accounts for subsequent differences in tolerance of the low oxygen conditions in this environment.



Publikationsverlauf

Artikel online veröffentlicht:
10. Oktober 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 West JB, Lahiri S, Maret KH, Peters Jr RM, Pizzo CJ. Barometric pressures at extreme altitudes on Mt. Everest: physiological significance. J Appl Physiol 1983; 54 (05) 1188-1194
  • 2 Brunt D. Physical and Dynamical Meteorology. Cambridge: Cambridge University Press; 1952
  • 3 Moore GWK, Semple JL. Weather and death on Mount Everest: an analysis of the into thin air storm. Bull Am Meteorol Soc 2006; 87: 465-480
  • 4 Bärtsch P, Swenson ER. Clinical practice: acute high-altitude illnesses. N Engl J Med 2013; 368 (24) 2294-2302
  • 5 Roach EB, Bleiberg J, Lathan CE, Wolpert L, Tsao JW, Roach RC. AltitudeOmics: decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment. Neuroreport 2014; 25 (11) 814-818
  • 6 Subudhi AW, Bourdillon N, Bucher J. et al. AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent. PLoS One 2014; 9 (03) e92191
  • 7 Latshang TD, Turk AJ, Hess T. et al. Acclimatization improves submaximal exercise economy at 5533 m. Scand J Med Sci Sports 2013; 23 (04) 458-467
  • 8 Moore LG. Measuring high-altitude adaptation. J Appl Physiol 2017; 123 (05) 1371-1385
  • 9 Clement ID, Bascom DA, Conway J. et al. An assessment of central-peripheral ventilatory chemoreflex interaction in humans. Respir Physiol 1992; 88 (1–2): 87-100
  • 10 Clement ID, Pandit JJ, Bascom DA, Dorrington KL, O'Connor DF, Robbins PA. An assessment of central-peripheral ventilatory chemoreflex interaction using acid and bicarbonate infusions in humans. J Physiol 1995; 485 (Pt 2): 561-570
  • 11 Fatemian M, Nieuwenhuijs DJ, Teppema LJ. et al. The respiratory response to carbon dioxide in humans with unilateral and bilateral resections of the carotid bodies. J Physiol 2003; 549 (Pt 3): 965-973
  • 12 Powell FL, Milsom WK, Mitchell GS. Time domains of the hypoxic ventilatory response. Respir Physiol 1998; 112 (02) 123-134
  • 13 Timmers HJ, Karemaker JM, Wieling W, Marres HA, Folgering HT, Lenders JW. Baroreflex and chemoreflex function after bilateral carotid body tumor resection. J Hypertens 2003; 21 (03) 591-599
  • 14 Luks AM, Ainslie PN, Lawley JS, Roach RC, Simonson TS. Ward, Milledge and West's High Altitude Medicine and Physiology. Boca Raton, FL: CRC Press; 2021
  • 15 Rahn H, Otis AB. Man's respiratory response during and after acclimatization to high altitude. Am J Physiol 1949; 157 (03) 445-462
  • 16 Vizek M, Pickett CK, Weil JV. Biphasic ventilatory response of adult cats to sustained hypoxia has central origin. J Appl Physiol 1987; 63 (04) 1658-1664
  • 17 Pamenter ME, Powell FL. Time domains of the hypoxic ventilatory response and their molecular basis. Compr Physiol 2016; 6 (03) 1345-1385
  • 18 Wagner PD. Gas exchange. In: Hornbein TF, Schoene RB, eds. High Altitude: An Exploration of Human Adaptation. New York, NY: Marcel Dekker Inc; 2001: 199-234
  • 19 West JB. Human physiology at extreme altitudes on Mount Everest. Science 1984; 223 (4638): 784-788
  • 20 Houston CS, Sutton JR, Cymerman A, Reeves JT. Operation Everest II: man at extreme altitude. J Appl Physiol 1987; 63 (02) 877-882
  • 21 West JB. American medical research expedition to Everest. High Alt Med Biol 2010; 11 (02) 103-110
  • 22 Grocott MP, Martin DS, Levett DZ, McMorrow R, Windsor J, Montgomery HE. Caudwell Xtreme Everest Research Group. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009; 360 (02) 140-149
  • 23 Bernardi L, Schneider A, Pomidori L, Paolucci E, Cogo A. Hypoxic ventilatory response in successful extreme altitude climbers. Eur Respir J 2006; 27 (01) 165-171
  • 24 Sharma S, Hashmi MF, Burns B. Alveolar Gas Equation. Treasure Island, FL: StatPearls; 2022
  • 25 Sato M, Severinghaus JW, Powell FL, Xu FD, Spellman Jr MJ. Augmented hypoxic ventilatory response in men at altitude. J Appl Physiol 1992; 73 (01) 101-107
  • 26 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 (04) 586-592
  • 27 Sorensen SC, Cruz JC. Ventilatory response to a single breath of CO2 in O2 in normal man at sea level and high altitude. J Appl Physiol 1969; 27 (02) 186-190
  • 28 Howard LS, Robbins PA. Ventilatory response to 8 h of isocapnic and poikilocapnic hypoxia in humans. J Appl Physiol 1995; 78 (03) 1092-1097
  • 29 Subudhi AW, Fan JL, Evero O. et al. AltitudeOmics: cerebral autoregulation during ascent, acclimatization, and re-exposure to high altitude and its relation with acute mountain sickness. J Appl Physiol 2014; 116 (07) 724-729
  • 30 Tenney SM, Remmers JE, Mithoefer JC. Interaction of CO2 and hypoxic stimuli on ventilation at high altitude. Q J Exp Physiol Cogn Med Sci 1963; 48: 192-201
  • 31 Fan JL, Burgess KR, Thomas KN. et al. Influence of indomethacin on ventilatory and cerebrovascular responsiveness to CO2 and breathing stability: the influence of PCO2 gradients. Am J Physiol Regul Integr Comp Physiol 2010; 298 (06) R1648-R1658
  • 32 Krapf R, Beeler I, Hertner D, Hulter HN. Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med 1991; 324 (20) 1394-1401
  • 33 Schoene RB, Roach RC, Hackett PH, Sutton JR, Cymerman A, Houston CS. Operation Everest II: ventilatory adaptation during gradual decompression to extreme altitude. Med Sci Sports Exerc 1990; 22 (06) 804-810
  • 34 Ainslie PN, Lucas SJ, Burgess KR. Breathing and sleep at high altitude. Respir Physiol Neurobiol 2013; 188 (03) 233-256
  • 35 Weil JV, Byrne-Quinn E, Sodal IE. et al. Hypoxic ventilatory drive in normal man. J Clin Invest 1970; 49 (06) 1061-1072
  • 36 Weil JV. Variation in human ventilatory control-genetic influence on the hypoxic ventilatory response. Respir Physiol Neurobiol 2003; 135 (2–3): 239-246
  • 37 Bird JD, Leacy JK, Foster GE. et al. Time course and magnitude of ventilatory and renal acid-base acclimatization following rapid ascent to and residence at 3,800 m over nine days. J Appl Physiol 2021; 130 (06) 1705-1715
  • 38 Milledge JS, Beeley JM, Broome J, Luff N, Pelling M, Smith D. Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response. Eur Respir J 1991; 4 (08) 1000-1003
  • 39 Sharma G, Goodwin J. Effect of aging on respiratory system physiology and immunology. Clin Interv Aging 2006; 1 (03) 253-260
  • 40 Byrne-Quinn E, Weil JV, Sodal IE, Filley GF, Grover RF. Ventilatory control in the athlete. J Appl Physiol 1971; 30 (01) 91-98
  • 41 Sareban M, Schiefer LM, Macholz F. et al. Endurance athletes are at increased risk for early acute mountain sickness at 3450 m. Med Sci Sports Exerc 2020; 52 (05) 1109-1115
  • 42 West JB, Wagner PD. Predicted gas exchange on the summit of Mt. Everest. Respir Physiol 1980; 42 (01) 1-16
  • 43 Wagner PD, Sutton JR, Reeves JT, Cymerman A, Groves BM, Malconian MK. Operation Everest II: pulmonary gas exchange during a simulated ascent of Mt. Everest. J Appl Physiol 1987; 63 (06) 2348-2359
  • 44 Cremona G, Asnaghi R, Baderna P. et al. Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study. Lancet 2002; 359 (9303): 303-309
  • 45 Dehnert C, Risse F, Ley S. et al. Magnetic resonance imaging of uneven pulmonary perfusion in hypoxia in humans. Am J Respir Crit Care Med 2006; 174 (10) 1132-1138
  • 46 Lovering AT, Kelly TS, DiMarco KG, Bradbury KE, Charkoudian N. Implications of a patent foramen ovale for environmental physiology and pathophysiology: do we know the 'hole' story?. J Physiol 2022; 600 (07) 1541-1553
  • 47 Lovering AT, Duke JW, Elliott JE. Intrapulmonary arteriovenous anastomoses in humans–response to exercise and the environment. J Physiol 2015; 593 (03) 507-520
  • 48 Gautier H, Peslin R, Grassino A. et al. Mechanical properties of the lungs during acclimatization to altitude. J Appl Physiol 1982; 52 (06) 1407-1415
  • 49 Senn O, Clarenbach CF, Fischler M. et al. Do changes in lung function predict high-altitude pulmonary edema at an early stage?. Med Sci Sports Exerc 2006; 38 (09) 1565-1570
  • 50 Welsh CH, Wagner PD, Reeves JT. et al. Operation Everest. II: spirometric and radiographic changes in acclimatized humans at simulated high altitudes. Am Rev Respir Dis 1993; 147 (05) 1239-1244
  • 51 Mason NP, Barry PW, Pollard AJ. et al. Serial changes in spirometry during an ascent to 5,300 m in the Nepalese Himalayas. High Alt Med Biol 2000; 1 (03) 185-195
  • 52 Mansell A, Powles A, Sutton J. Changes in pulmonary PV characteristics of human subjects at an altitude of 5,366 m. J Appl Physiol 1980; 49 (01) 79-83
  • 53 Finkelstein S, Tomashefski JF, Shillito FH. Pulmonary mechanics at altitude in normal and obstructive lung disease patients. Aerosp Med 1965; 36: 880-884
  • 54 Dehnert C, Luks AM, Schendler G. et al. No evidence for interstitial lung oedema by extensive pulmonary function testing at 4,559 m. Eur Respir J 2010; 35 (04) 812-820
  • 55 Deboeck G, Moraine JJ, Naeije R. Respiratory muscle strength may explain hypoxia-induced decrease in vital capacity. Med Sci Sports Exerc 2005; 37 (05) 754-758
  • 56 Swenson ER. Con: most climbers do not develop subclinical interstitial pulmonary edema. High Alt Med Biol 2011; 12 (02) 125-128 , discussion 129–130
  • 57 Jaeger JJ, Sylvester JT, Cymerman A, Berberich JJ, Denniston JC, Maher JT. Evidence for increased intrathoracic fluid volume in man at high altitude. J Appl Physiol 1979; 47 (04) 670-676
  • 58 Raymond L, Severinghaus JW. Static pulmonary compliance of man during altitude hypoxia. J Appl Physiol 1971; 31 (05) 785-787
  • 59 Forte Jr VA, Leith DE, Muza SR, Fulco CS, Cymerman A. Ventilatory capacities at sea level and high altitude. Aviat Space Environ Med 1997; 68 (06) 488-493
  • 60 Sharma S, Brown B. Spirometry and respiratory muscle function during ascent to higher altitudes. Lung 2007; 185 (02) 113-121
  • 61 Babcock MA, Johnson BD, Pegelow DF, Suman OE, Griffin D, Dempsey JA. Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy humans. J Appl Physiol 1995; 78 (01) 82-92
  • 62 Gudjonsdottir M, Appendini L, Baderna P. et al. Diaphragm fatigue during exercise at high altitude: the role of hypoxia and workload. Eur Respir J 2001; 17 (04) 674-680
  • 63 Newhouse MT, Becklake MR, MacKlem PT, McGregor M. Effect of alterations in end-tidal Co2 tension on flow resistance. J Appl Physiol 1964; 19: 745-749
  • 64 van den Elshout FJ, van Herwaarden CL, Folgering HT. Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. Thorax 1991; 46 (01) 28-32
  • 65 Mazzeo RS, Wolfel EE, Butterfield GE, Reeves JT. Sympathetic response during 21 days at high altitude (4,300 m) as determined by urinary and arterial catecholamines. Metabolism 1994; 43 (10) 1226-1232
  • 66 Pellegrino R, Pompilio P, Quaranta M. et al. Airway responses to methacholine and exercise at high altitude in healthy lowlanders. J Appl Physiol 2010; 108 (02) 256-265
  • 67 Pollard AJ, Mason NP, Barry PW. et al. Effect of altitude on spirometric parameters and the performance of peak flow meters. Thorax 1996; 51 (02) 175-178
  • 68 Pellegrino R, Viegi G, Brusasco V. et al. Interpretative strategies for lung function tests. Eur Respir J 2005; 26 (05) 948-968
  • 69 Cogo A, Basnyat B, Legnani D, Allegra L. Bronchial asthma and airway hyperresponsiveness at high altitude. Respiration 1997; 64 (06) 444-449
  • 70 von Euler US, Liljestrand G. Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 1946; 12: 301-320
  • 71 Levine BD, Zuckerman JH, deFilippi CR. Effect of high-altitude exposure in the elderly: the Tenth Mountain Division study. Circulation 1997; 96 (04) 1224-1232
  • 72 Smith TG, Talbot NP, Chang RW. et al. Pulmonary artery pressure increases during commercial air travel in healthy passengers. Aviat Space Environ Med 2012; 83 (07) 673-676
  • 73 Swenson ER, Robertson HT, Hlastala MP. Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. Am J Respir Crit Care Med 1994; 149 (06) 1563-1569
  • 74 Hopkins SR, Garg J, Bolar DS, Balouch J, Levin DL. Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema. Am J Respir Crit Care Med 2005; 171 (01) 83-87
  • 75 Grünig E, Mereles D, Hildebrandt W. et al. Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol 2000; 35 (04) 980-987
  • 76 Talbot NP, Balanos GM, Dorrington KL, Robbins PA. Two temporal components within the human pulmonary vascular response to approximately 2 h of isocapnic hypoxia. J Appl Physiol 2005; 98 (03) 1125-1139
  • 77 Smith KA, Schumacker PT. Sensors and signals: the role of reactive oxygen species in hypoxic pulmonary vasoconstriction. J Physiol 2019; 597 (04) 1033-1043
  • 78 Vejlstrup NG, O'Neill M, Nagyova B, Dorrington KL. Time course of hypoxic pulmonary vasoconstriction: a rabbit model of regional hypoxia. Am J Respir Crit Care Med 1997; 155 (01) 216-221
  • 79 Bailey DM, Dehnert C, Luks AM. et al. High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability. J Physiol 2010; 588 (Pt 23): 4837-4847
  • 80 Berger MM, Hesse C, Dehnert C. et al. Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema. Am J Respir Crit Care Med 2005; 172 (06) 763-767
  • 81 Berger MM, Dehnert C, Bailey DM. et al. Transpulmonary plasma ET-1 and nitrite differences in high altitude pulmonary hypertension. High Alt Med Biol 2009; 10 (01) 17-24
  • 82 Swenson ER. Hypoxic pulmonary vasoconstriction. High Alt Med Biol 2013; 14 (02) 101-110
  • 83 Dunham-Snary KJ, Wu D, Sykes EA. et al. Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest 2017; 151 (01) 181-192
  • 84 Subedi P, Gasho C, Stembridge M. et al. Pulmonary vascular reactivity to supplemental oxygen in Sherpa and lowlanders during gradual ascent to high altitude. Exp Physiol 2023; 108 (01) 111-122
  • 85 Berger MM, Bailey DM. On the mechanisms underlying activation and reversal of high altitude-induced pulmonary hypertension in humans - another piece in the pulmonary puzzle. Exp Physiol 2023; 108 (01) 1-4
  • 86 Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev 2012; 92 (01) 367-520
  • 87 Pugh CW. Modulation of the hypoxic response. Adv Exp Med Biol 2016; 903: 259-271
  • 88 Shimoda LA, Laurie SS. HIF and pulmonary vascular responses to hypoxia. J Appl Physiol 2014; 116 (07) 867-874
  • 89 Shimoda LA. Cellular pathways promoting pulmonary vascular remodeling by hypoxia. Physiology (Bethesda) 2020; 35 (04) 222-233
  • 90 Sydykov A, Mamazhakypov A, Maripov A. et al. Pulmonary hypertension in acute and chronic high altitude maladaptation disorders. Int J Environ Res Public Health 2021; 18 (04) 18
  • 91 Vogel JA, Harris CW. Cardiopulmonary responses of resting man during early exposure to high altitude. J Appl Physiol 1967; 22 (06) 1124-1128
  • 92 Koller EA, Drechsel S, Hess T, Macherel P, Boutellier U. Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man. Eur J Appl Physiol Occup Physiol 1988; 57 (02) 163-172
  • 93 Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol 2003; 546 (Pt 3): 921-929
  • 94 Siebenmann C, Rasmussen P, Sørensen H. et al. Hypoxia increases exercise heart rate despite combined inhibition of β-adrenergic and muscarinic receptors. Am J Physiol Heart Circ Physiol 2015; 308 (12) H1540-H1546
  • 95 Reeves JT, Groves BM, Sutton JR. et al. Operation Everest II: preservation of cardiac function at extreme altitude. J Appl Physiol 1987; 63 (02) 531-539
  • 96 Siebenmann C, Hug M, Keiser S. et al. Hypovolemia explains the reduced stroke volume at altitude. Physiol Rep 2013; 1 (05) e00094
  • 97 Swenson ER. Renal function and fluid homeostasis. In: Hornbein TF, Schoene RB, eds. An Exploration of Human Adaptation. New York, NY: Marcel Dekker; 2001: 525-568
  • 98 Schlittler M, Gatterer H, Turner R. et al. Regulation of plasma volume in male lowlanders during 4 days of exposure to hypobaric hypoxia equivalent to 3500 m altitude. J Physiol 2021; 599 (04) 1083-1096
  • 99 Suarez J, Alexander JK, Houston CS. Enhanced left ventricular systolic performance at high altitude during Operation Everest II. Am J Cardiol 1987; 60 (01) 137-142
  • 100 Stembridge M, Levine BD. No heartbreak at high altitude; preserved cardiac function in chronic hypoxia. Exp Physiol 2019; 104 (05) 619-620
  • 101 Keyes LE, Sallade TD, Duke C. et al. Blood pressure and altitude: an observational cohort study of hypertensive and nonhypertensive Himalayan trekkers in Nepal. High Alt Med Biol 2017; 18 (03) 267-277
  • 102 Wolfel EE, Selland MA, Mazzeo RS, Reeves JT. Systemic hypertension at 4,300 m is related to sympathoadrenal activity. J Appl Physiol 1994; 76 (04) 1643-1650
  • 103 Parati G, Bilo G, Faini A. et al. Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial. Eur Heart J 2014; 35 (44) 3113-3122
  • 104 Kaufmann PA, Schirlo C, Pavlicek V. et al. Increased myocardial blood flow during acute exposure to simulated altitudes. J Nucl Cardiol 2001; 8 (02) 158-164
  • 105 Wyss CA, Koepfli P, Fretz G, Seebauer M, Schirlo C, Kaufmann PA. Influence of altitude exposure on coronary flow reserve. Circulation 2003; 108 (10) 1202-1207
  • 106 Wolfel EE, Groves BM, Brooks GA. et al. Oxygen transport during steady-state submaximal exercise in chronic hypoxia. J Appl Physiol 1991; 70 (03) 1129-1136
  • 107 Singh MV, Rawal SB, Tyagi AK. Body fluid status on induction, reinduction and prolonged stay at high altitude of human volunteers. Int J Biometeorol 1990; 34 (02) 93-97
  • 108 Milledge JS, Cotes PM. Serum erythropoietin in humans at high altitude and its relation to plasma renin. J Appl Physiol 1985; 59 (02) 360-364
  • 109 Mairbäurl H, Schobersberger W, Humpeler E, Hasibeder W, Fischer W, Raas E. Beneficial effects of exercising at moderate altitude on red cell oxygen transport and on exercise performance. Pflugers Arch 1986; 406 (06) 594-599
  • 110 Winslow RM, Samaja M, West JB. Red cell function at extreme altitude on Mount Everest. J Appl Physiol 1984; 56 (01) 109-116
  • 111 Martin DS, Pate JS, Vercueil A, Doyle PW, Mythen MG, Grocott MP. Caudwell Xtreme Everest Research Group. Reduced coagulation at high altitude identified by thromboelastography. Thromb Haemost 2012; 107 (06) 1066-1071
  • 112 Hoiland RL, Bain AR, Rieger MG, Bailey DM, Ainslie PN. Hypoxemia, oxygen content, and the regulation of cerebral blood flow. Am J Physiol Regul Integr Comp Physiol 2016; 310 (05) R398-R413
  • 113 Ainslie PN, Subudhi AW. Cerebral blood flow at high altitude. High Alt Med Biol 2014; 15 (02) 133-140
  • 114 Lucas SJ, Burgess KR, Thomas KN. et al. Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m. J Physiol 2011; 589 (Pt 3): 741-753
  • 115 Boutellier U, Howald H, di Prampero PE, Giezendanner D, Cerretelli P. Human muscle adaptations to chronic hypoxia. Prog Clin Biol Res 1983; 136: 273-285
  • 116 Cerretelli P, Marconi C, Dériaz O, Giezendanner D. After effects of chronic hypoxia on cardiac output and muscle blood flow at rest and exercise. Eur J Appl Physiol Occup Physiol 1984; 53 (02) 92-96
  • 117 Hoppeler H, Howald H, Cerretelli P. Human muscle structure after exposure to extreme altitude. Experientia 1990; 46 (11–12): 1185-1187
  • 118 Chaillou T. Skeletal muscle fiber type in hypoxia: adaptation to high-altitude exposure and under conditions of pathological hypoxia. Front Physiol 2018; 9: 1450
  • 119 Levett DZ, Radford EJ, Menassa DA. et al; Caudwell Xtreme Everest Research Group. Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest. FASEB J 2012; 26 (04) 1431-1441
  • 120 Schmidt M, Gerlach F, Avivi A. et al. Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem 2004; 279 (09) 8063-8069
  • 121 Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 2012; 148 (03) 399-408
  • 122 Reite M, Jackson D, Cahoon RL, Weil JV. Sleep physiology at high altitude. Electroencephalogr Clin Neurophysiol 1975; 38 (05) 463-471
  • 123 Berssenbrugge A, Dempsey J, Iber C, Skatrud J, Wilson P. Mechanisms of hypoxia-induced periodic breathing during sleep in humans. J Physiol 1983; 343: 507-524
  • 124 Bloch KE, Latshang TD, Turk AJ. et al. Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m). Am J Respir Crit Care Med 2010; 182 (04) 562-568
  • 125 Weil JV, Kryger MH, Scroggin CH. Sleep and breathing at high altitude. In: Guilleminault C, Dement, W. C., eds, ed. Sleep Apnea Syndromes. New York, NY: Alan R Liss; 1978: 119-123
  • 126 Wickramasinghe H, Anholm JD. Sleep and breathing at high altitude. Sleep Breath 1999; 3 (03) 89-102
  • 127 Joern AT, Shurley JT, Brooks RE, Guenter CA, Pierce CM. Short-term changes in sleep patterns on arrival at the South Polar Plateau. Arch Intern Med 1970; 125 (04) 649-654
  • 128 Anholm JD, Powles AC, Downey III R. et al. Operation Everest II: arterial oxygen saturation and sleep at extreme simulated altitude. Am Rev Respir Dis 1992; 145 (4, Pt 1): 817-826
  • 129 Pappenheimer JR. Sleep and respiration of rats during hypoxia. J Physiol 1977; 266 (01) 191-207
  • 130 Zieliński J, Koziej M, Mańkowski M. et al. The quality of sleep and periodic breathing in healthy subjects at an altitude of 3,200 m. High Alt Med Biol 2000; 1 (04) 331-336
  • 131 Cherniack NS, Longobardo GS. Mathematical models of periodic breathing and their usefulness in understanding cardiovascular and respiratory disorders. Exp Physiol 2006; 91 (02) 295-305
  • 132 Khoo MC, Kronauer RE, Strohl KP, Slutsky AS. Factors inducing periodic breathing in humans: a general model. J Appl Physiol 1982; 53 (03) 644-659
  • 133 Javaheri S, Dempsey JA. Central sleep apnea. Compr Physiol 2013; 3 (01) 141-163
  • 134 Burgess KR, Ainslie PN. Central sleep apnea at high altitude. Adv Exp Med Biol 2016; 903: 275-283
  • 135 Lahiri S, Maret K, Sherpa MG. Dependence of high altitude sleep apnea on ventilatory sensitivity to hypoxia. Respir Physiol 1983; 52 (03) 281-301
  • 136 Luks AM, van Melick H, Batarse RR, Powell FL, Grant I, West JB. Room oxygen enrichment improves sleep and subsequent day-time performance at high altitude. Respir Physiol 1998; 113 (03) 247-258
  • 137 Hackett PH, Roach RC, Harrison GL, Schoene RB, Mills Jr WJ. Respiratory stimulants and sleep periodic breathing at high altitude. Almitrine versus acetazolamide. Am Rev Respir Dis 1987; 135 (04) 896-898
  • 138 Fischer R, Lang SM, Leitl M, Thiere M, Steiner U, Huber RM. Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude. Eur Respir J 2004; 23 (01) 47-52
  • 139 Beaumont M, Goldenberg F, Lejeune D, Marotte H, Harf A, Lofaso F. Effect of zolpidem on sleep and ventilatory patterns at simulated altitude of 4,000 meters. Am J Respir Crit Care Med 1996; 153 (6, Pt 1): 1864-1869
  • 140 Nickol AH, Leverment J, Richards P. et al. Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study. J Sleep Res 2006; 15 (04) 445-454
  • 141 Cerretelli P. Gas exchange at high altitude. In: West JB, ed. Pulmonary Gas Exchange. New York, NY: Academic Press; 1980: 97-147
  • 142 Fulco CS, Rock PB, Cymerman A. Maximal and submaximal exercise performance at altitude. Aviat Space Environ Med 1998; 69 (08) 793-801
  • 143 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 Regul Integr Comp Physiol 2003; 284 (02) R304-R316
  • 144 Ghofrani HA, Reichenberger F, Kohstall MG. et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med 2004; 141 (03) 169-177
  • 145 Amann M, Romer LM, Pegelow DF, Jacques AJ, Hess CJ, Dempsey JA. Effects of arterial oxygen content on peripheral locomotor muscle fatigue. J Appl Physiol 2006; 101 (01) 119-127
  • 146 Amann M, Romer LM, Subudhi AW, Pegelow DF, Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 2007; 581 (Pt 1): 389-403
  • 147 Bärtsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation 2007; 116 (19) 2191-2202
  • 148 Lundby C, Sander M, van Hall G, Saltin B, Calbet JA. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J Physiol 2006; 573 (Pt 2): 535-547
  • 149 Mourot L. Limitation of maximal heart rate in hypoxia: mechanisms and clinical importance. Front Physiol 2018; 9: 972
  • 150 West JB, Boyer SJ, Graber DJ. et al. Maximal exercise at extreme altitudes on Mount Everest. J Appl Physiol 1983; 55 (03) 688-698
  • 151 Chapman RF, Karlsen T, Ge RL, Stray-Gundersen J, Levine BD. Living altitude influences endurance exercise performance change over time at altitude. J Appl Physiol 2016; 120 (10) 1151-1158
  • 152 Hackett PH, Luks AM, Lawley JS, Roach RC. High altitude medicine and pathophysiology. In: Auerbach PS, ed. Auerbach's Wilderness Medicine. Philadelphia, PA: Elsevier; 2017: 8-29
  • 153 Pugh LG. Man at high altitude: studies carried out in the Himalaya. Sci Basis Med Annu Rev 1964; 32-54
  • 154 Smith TG, Dempsey JA, Hornbein TF. Control of breathing at high altitude. In: Hornbein TF, Schoene RB, eds. High Altitude: An Exploration of Human Adaptation (Lung Biology in Health and Disease). New York, NY: Marcel Dekker; 2001: 140-148
  • 155 Pace Nello. Man at altitude. In: Farber SM, Wilson RHL. eds. The Air We Breathe: A Study of Man and His Environment. Springfield, MA: Charles C. Thomas; 1961: 53-70
  • 156 Dehnert C, Grünig E, Mereles D, von Lennep N, Bärtsch P. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude. Eur Respir J 2005; 25 (03) 545-551
  • 157 Rimoldi SF, Sartori C, Seiler C. et al. High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations. Prog Cardiovasc Dis 2010; 52 (06) 512-524