Cardiovascular physiology and pathophysiology at high altitude.


Journal

Nature reviews. Cardiology
ISSN: 1759-5010
Titre abrégé: Nat Rev Cardiol
Pays: England
ID NLM: 101500075

Informations de publication

Date de publication:
02 Oct 2023
Historique:
accepted: 16 08 2023
medline: 3 10 2023
pubmed: 3 10 2023
entrez: 2 10 2023
Statut: aheadofprint

Résumé

Oxygen is vital for cellular metabolism; therefore, the hypoxic conditions encountered at high altitude affect all physiological functions. Acute hypoxia activates the adrenergic system and induces tachycardia, whereas hypoxic pulmonary vasoconstriction increases pulmonary artery pressure. After a few days of exposure to low oxygen concentrations, the autonomic nervous system adapts and tachycardia decreases, thereby protecting the myocardium against high energy consumption. Permanent exposure to high altitude induces erythropoiesis, which if excessive can be deleterious and lead to chronic mountain sickness, often associated with pulmonary hypertension and heart failure. Genetic factors might account for the variable prevalence of chronic mountain sickness, depending on the population and geographical region. Cardiovascular adaptations to hypoxia provide a remarkable model of the regulation of oxygen availability at the cellular and systemic levels. Rapid exposure to high altitude can have adverse effects in patients with cardiovascular diseases. However, intermittent, moderate hypoxia might be useful in the management of some cardiovascular disorders, such as coronary heart disease and heart failure. The aim of this Review is to help physicians to understand the cardiovascular responses to hypoxia and to outline some recommendations that they can give to patients with cardiovascular disease who wish to travel to high-altitude destinations.

Identifiants

pubmed: 37783743
doi: 10.1038/s41569-023-00924-9
pii: 10.1038/s41569-023-00924-9
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. Springer Nature Limited.

Références

Pace, N., Consolazio, W. V. & Lozner, E. L. The effect of transfusions of red blood cells on the hypoxia tolerance of normal men. Science 102, 589–591 (1945).
pubmed: 17843173 doi: 10.1126/science.102.2658.589
Wiggers, C. J. Cardiac adaptations in acute progressive anoxia. Ann. Intern. Med. 14, 1237–1247 (1941).
doi: 10.7326/0003-4819-14-7-1237
Richalet, J.-P. The invention of hypoxia. J. Appl. Physiol. 130, 1573–1582 (2021).
pubmed: 33703942 doi: 10.1152/japplphysiol.00936.2020
Berner, R. A. Phanerozoic atmospheric oxygen: new results using the GEOCARBSULF model. Am. J. Sci. 309, 603–606 (2009).
doi: 10.2475/07.2009.03
Payne, J. L. et al. The evolutionary consequences of oxygenic photosynthesis: a body size perspective. Photosynth. Res. 107, 37–57 (2011).
pubmed: 20821265 doi: 10.1007/s11120-010-9593-1
Saugy, J. J. et al. Same performance changes after live high-train low in normobaric vs. hypobaric hypoxia. Front. Physiol. 7, 138 (2016).
pubmed: 27148076 pmcid: 4835493 doi: 10.3389/fphys.2016.00138
Semenza, G. L. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology 24, 97–106 (2009).
pubmed: 19364912 doi: 10.1152/physiol.00045.2008
Sommer, N., Strielkov, I., Pak, O. & Weissmann, N. Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction. Eur. Respir. J. 47, 288–303 (2016).
pubmed: 26493804 doi: 10.1183/13993003.00945-2015
Luks, A. et al. Ward, Milledge and West’s High Altitude Medicine and Physiology 6th edn (CRC Press, 2021).
Wehrlin, J. P. & Hallén, J. Linear decrease in VO2max and performance with increasing altitude in endurance athletes. Eur. J. Appl. Physiol. 96, 404–412 (2006).
pubmed: 16311764 doi: 10.1007/s00421-005-0081-9
Richalet, J.-P. & Lhuissier, F. J. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt. Med. Biol. 16, 117–124 (2015).
pubmed: 25946570 doi: 10.1089/ham.2015.0030
Dehnert, C. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude. Eur. Respir. J. 25, 545–551 (2005).
pubmed: 15738301 doi: 10.1183/09031936.05.00070404
León-Velarde, F. & Richalet, J.-P. Respiratory control in residents at high altitude: physiology and pathophysiology. High Alt. Med. Biol. 7, 125–137 (2006).
pubmed: 16764526 doi: 10.1089/ham.2006.7.125
Richalet, J.-P. in Hypoxia: Translation in Progress (eds Roach, R. C., Hackett, P. H. & Wagner, P. D.) Ch. 23, 343–356 (Springer, 2016).
Escourrou, P., Johnson, D. G. & Rowell, L. B. Hypoxemia increases plasma catecholamine concentrations in exercising humans. J. Appl. Physiol. 57, 1507–1511 (1984).
pubmed: 6520045 doi: 10.1152/jappl.1984.57.5.1507
Calbet, J. A. L. Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans. J. Physiol. 551, 379–386 (2003).
pubmed: 12844510 pmcid: 2343162 doi: 10.1113/jphysiol.2003.045112
Hansen, J. & Sander, M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J. Physiol. 546, 921–929 (2003).
pubmed: 12563015 doi: 10.1113/jphysiol.2002.031765
Kacimi, R. et al. Differential regulation of G protein expression in rat hearts exposed to chronic hypoxia. Am. J. Physiol. Heart Circ. Physiol. 269, H1865–H1873 (1995).
doi: 10.1152/ajpheart.1995.269.6.H1865
Boussi, L. & Frishman, W. H. β-Arrestin as a therapeutic target in heart failure. Cardiol. Rev. 29, 223–229 (2021).
pubmed: 33093306 doi: 10.1097/CRD.0000000000000363
Cornolo, J., Mollard, P., Brugniaux, J. V., Robach, P. & Richalet, J.-P. Autonomic control of the cardiovascular system during acclimatization to high altitude: effects of sildenafil. J. Appl. Physiol. 97, 935–940 (2004).
pubmed: 15145924 doi: 10.1152/japplphysiol.00239.2004
Vogel, J. A. & Harris, C. W. Cardiopulmonary responses of resting man during early exposure to high altitude. J. Appl. Physiol. 22, 1124–1128 (1967).
pubmed: 5338456 doi: 10.1152/jappl.1967.22.6.1124
Richalet, J. & Hermand, E. Modeling the oxygen transport to the myocardium at maximal exercise at high altitude. Physiol. Rep. 10, e15262 (2022).
pubmed: 35439356 pmcid: 9017981 doi: 10.14814/phy2.15262
Kacimi, R., Richalet, J. P. & Crozatier, B. Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart. J. Appl. Physiol. 75, 1123–1128 (1993).
pubmed: 8226520 doi: 10.1152/jappl.1993.75.3.1123
León-Velarde, F. et al. Hypoxia- and normoxia-induced reversibility of autonomic control in Andean guinea pig heart. J. Appl. Physiol. 81, 2229–2234 (1996).
pubmed: 8941549 doi: 10.1152/jappl.1996.81.5.2229
León-Velarde, F. et al. Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R274–R281 (2001).
pubmed: 11124161 doi: 10.1152/ajpregu.2001.280.1.R274
Voelkel, N. F., Hegstrand, L., Reeves, J. T., McMurty, I. F. & Molinoff, P. B. Effects of hypoxia on density of beta-adrenergic receptors. J. Appl. Physiol. 50, 363–366 (1981).
pubmed: 6259101 doi: 10.1152/jappl.1981.50.2.363
Richalet, J. P. et al. Decreased cardiac response to isoproterenol infusion in acute and chronic hypoxia. J. Appl. Physiol. 65, 1957–1961 (1988).
pubmed: 2850290 doi: 10.1152/jappl.1988.65.5.1957
Richalet, J. P. et al. MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia. J. Nucl. Med. 31, 34–37 (1990).
pubmed: 2295937
Boushel, R. et al. Parasympathetic neural activity accounts for the lowering of exercise heart rate at high altitude. Circulation 104, 1785–1791 (2001).
pubmed: 11591615 doi: 10.1161/hc4001.097040
Clar, C., Dorrington, K. L., Fatemian, M. & Robbins, P. A. Effects of 8 h of isocapnic hypoxia with and without muscarinic blockade on ventilation and heart rate in humans. Exp. Physiol. 86, 529–538 (2001).
pubmed: 11445832 doi: 10.1113/eph8602174
Hartley, L. H., Vogel, J. A. & Cruz, J. C. Reduction of maximal exercise heart rate at altitude and its reversal with atropine. J. Appl. Physiol. 36, 362–365 (1974).
pubmed: 4814308 doi: 10.1152/jappl.1974.36.3.362
Favret, F., Richalet, J.-P., Henderson, K. K., Germack, R. & Gonzalez, N. C. Myocardial adrenergic and cholinergic receptor function in hypoxia: correlation with O
pubmed: 11171651 doi: 10.1152/ajpregu.2001.280.3.R730
Basnyat, B., Sill, D. & Gupta, V. Myocardial infarction or high-altitude pulmonary edema? Wilderness Environ. Med. 11, 196–198 (2000).
pubmed: 11055567 doi: 10.1580/1080-6032(2000)011[0196:MIOHAP]2.3.CO;2
Liggett, S. B. et al. A GRK5 polymorphism that inhibits β-adrenergic receptor signaling is protective in heart failure. Nat. Med. 14, 510–517 (2008).
pubmed: 18425130 pmcid: 2596476 doi: 10.1038/nm1750
Reeves, J. T. et al. Operation Everest II: preservation of cardiac function at extreme altitude. J. Appl. Physiol. 63, 531–539 (1987).
pubmed: 3654411 doi: 10.1152/jappl.1987.63.2.531
Grover, R. F., Weil, J. V. & Reeves, J. T. Cardiovascular adaptation to exercise at high altitude. Exerc. Sport Sci. Rev. 14, 269–302 (1986).
pubmed: 3525187 doi: 10.1249/00003677-198600140-00012
Fukuda, T. et al. Effects of acute hypoxia at moderate altitude on stroke volume and cardiac output during exercise. Int. Heart J. 51, 170–175 (2010).
pubmed: 20558906 doi: 10.1536/ihj.51.170
Boussuges, A. et al. Operation Everest III (Comex ’97): modifications of cardiac function secondary to altitude-induced hypoxia: an echocardiographic and Doppler study. Am. J. Respir. Crit. Care Med.  161, 264–270 (2000).
pubmed: 10619830 doi: 10.1164/ajrccm.161.1.9902096
Ghofrani, H. A. 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.  141, 169 (2004).
pubmed: 15289213 doi: 10.7326/0003-4819-141-3-200408030-00005
Brugniaux, J. V. et al. Living high-training low: tolerance and acclimatization in elite endurance athletes. Eur. J. Appl. Physiol. 96, 66–77 (2006).
pubmed: 16307279 doi: 10.1007/s00421-005-0065-9
Holloway, C. J. et al. Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp. FASEB J. 25, 792–796 (2011).
pubmed: 20978235 doi: 10.1096/fj.10-172999
Brito, J. et al. Chronic intermittent hypoxia at high altitude exposure for over 12 years: assessment of hematological, cardiovascular, and renal effects. High Alt. Med. Biol. 8, 236–244 (2007).
pubmed: 17824824 doi: 10.1089/ham.2007.8310
Richalet, J.-P. et al. Chilean miners commuting from sea level to 4500 m: a prospective study. High Alt. Med. Biol. 3, 159–166 (2002).
pubmed: 12162860 doi: 10.1089/15270290260131894
Richalet, J.-P. Operation Everest III: COMEX ’97. High Alt. Med. Biol. 11, 121–132 (2010).
pubmed: 20586596 doi: 10.1089/ham.2009.1099
Huez, S., Faoro, V., Guénard, H., Martinot, J.-B. & Naeije, R. Echocardiographic and tissue Doppler imaging of cardiac adaptation to high altitude in native highlanders versus acclimatized lowlanders. Am. J. Cardiol. 103, 1605–1609 (2009).
pubmed: 19463523 doi: 10.1016/j.amjcard.2009.02.006
Coustet, B., Lhuissier, F. J., Vincent, R. & Richalet, J.-P. Electrocardiographic changes during exercise in acute hypoxia and susceptibility to severe high-altitude illnesses. Circulation 131, 786–794 (2015).
pubmed: 25561515 doi: 10.1161/CIRCULATIONAHA.114.013144
Deussen, A., Ohanyan, V., Jannasch, A., Yin, L. & Chilian, W. Mechanisms of metabolic coronary flow regulation. J. Mol. Cell Cardiol. 52, 794–801 (2012).
pubmed: 22004900 doi: 10.1016/j.yjmcc.2011.10.001
Grubbström, J., Berglund, B. & Kaijser, L. Myocardial oxygen supply and lactate metabolism during marked arterial hypoxaemia. Acta Physiol. Scand. 149, 303–310 (1993).
pubmed: 8310835 doi: 10.1111/j.1748-1716.1993.tb09625.x
Wyss, C. A. et al. Influence of altitude exposure on coronary flow reserve. Circulation 108, 1202–1207 (2003).
pubmed: 12939217 doi: 10.1161/01.CIR.0000087432.63671.2E
Hainsworth, R., Drinkhill, M. J. & Rivera-Chira, M. The autonomic nervous system at high altitude. Clin. Auton. Res. 17, 13–19 (2007).
pubmed: 17264976 pmcid: 1797062 doi: 10.1007/s10286-006-0395-7
Bruno, R. M. et al. Sympathetic regulation of vascular function in health and disease. Front. Physiol. 3, 284 (2012).
pubmed: 22934037 pmcid: 3429057 doi: 10.3389/fphys.2012.00284
Bilo, G. et al. Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude. J. Hypertens. 29, 380–387 (2011).
pubmed: 21045724 doi: 10.1097/HJH.0b013e3283409014
Parati, G. et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. Eur. Heart J. 34, 759–766 (2013).
pubmed: 22711752 doi: 10.1093/eurheartj/ehs140
Parati, G. 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. 35, 3113–3122 (2014).
pubmed: 25161182 doi: 10.1093/eurheartj/ehu275
Casey, D. P. & Joyner, M. J. Compensatory vasodilatation during hypoxic exercise: mechanisms responsible for matching oxygen supply to demand. J. Physiol.  590, 6321–6326 (2012).
pubmed: 22988134 pmcid: 3533194 doi: 10.1113/jphysiol.2012.242396
Richalet, J.-P., Larmignat, P., Poitrine, E., Letournel, M. & Canouï-Poitrine, F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am. J. Respir. Crit. Care Med.  185, 192–198 (2012).
pubmed: 22071330 doi: 10.1164/rccm.201108-1396OC
Canouï-Poitrine, F. et al. Risk prediction score for severe high altitude illness: a cohort study. PLoS One 9, e100642 (2014).
doi: 10.1371/journal.pone.0100642
Richalet, J.-P. et al. Validation of a score for the detection of subjects with high risk for severe high-altitude illness. Med. Sci. Sports Exercise 53, 1294–1302 (2021).
doi: 10.1249/MSS.0000000000002586
Vogel, J. A., Hansen, J. E. & Harris, C. W. Cardiovascular responses in man during exhaustive work at sea level and high altitude. J. Appl. Physiol.  23, 531–539 (1967).
pubmed: 6053679 doi: 10.1152/jappl.1967.23.4.531
Winkler, L., Lhuissier, F. J. & Richalet, J.-P. Systemic blood pressure at exercise in hypoxia in hypertensive and normotensive patients. J. Hypertens. 35, 2402–2410 (2017).
pubmed: 28704259 doi: 10.1097/HJH.0000000000001479
Mallet, R. T., Burtscher, J., Richalet, J.-P., Millet, G. P. & Burtscher, M. Impact of high altitude on cardiovascular health: current perspectives. Vasc. Health Risk Manag. 17, 317–335 (2021).
pubmed: 34135590 pmcid: 8197622 doi: 10.2147/VHRM.S294121
Savard, G. K., Areskog, N. H. & Saltin, B. Cardiovascular response to exercise in humans following acclimatization to extreme altitude. Acta Physiol. Scand. 154, 499–509 (1995).
pubmed: 7484176 doi: 10.1111/j.1748-1716.1995.tb09935.x
Wolfel, E. E. et al. Oxygen transport during steady-state submaximal exercise in chronic hypoxia. J. Appl. Physiol. 70, 1129–1136 (1991).
pubmed: 2032978 doi: 10.1152/jappl.1991.70.3.1129
Wolfel, E. E. et al. O
pubmed: 9729588 doi: 10.1152/jappl.1998.85.3.1092
Zhou, Q. et al. A randomly-controlled study on the cardiac function at the early stage of return to the plains after short-term exposure to high altitude. PLoS ONE 7, e31097 (2012).
pubmed: 22363556 pmcid: 3281922 doi: 10.1371/journal.pone.0031097
Keyes, L. E. et al. Blood pressure and altitude: an observational cohort study of hypertensive and nonhypertensive Himalayan trekkers in Nepal. High Alt. Med. Biol.  18, 267–277 (2017).
pubmed: 28787190 doi: 10.1089/ham.2017.0001
Tremblay, J. C. et al. Endothelial function and shear stress in hypobaric hypoxia: time course and impact of plasma volume expansion in men. Am. J. Physiol. Heart Circ. Physiol. 319, H980–H994 (2020).
pubmed: 32886005 doi: 10.1152/ajpheart.00597.2020
Rieger, M. G. et al. Cardiopulmonary and cerebrovascular acclimatization in children and adults at 3800 m. J. Physiol. 600, 4849–4863 (2022).
pubmed: 36165275 doi: 10.1113/JP283419
Talbot, N. P., Balanos, G. M., Dorrington, K. L. & Robbins, P. A. Two temporal components within the human pulmonary vascular response to approximately 2 h of isocapnic hypoxia. J. Appl. Physiol. 98, 1125–1139 (2005).
pubmed: 15542574 doi: 10.1152/japplphysiol.00903.2004
Groves, B. M. et al. Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen. J. Appl. Physiol. 63, 521–530 (1987).
pubmed: 3654410 doi: 10.1152/jappl.1987.63.2.521
Moudgil, R., Michelakis, E. D. & Archer, S. L. Hypoxic pulmonary vasoconstriction. J. Appl. Physiol.  98, 390–403 (2005).
pubmed: 15591309 doi: 10.1152/japplphysiol.00733.2004
Stenmark, K. R., Fagan, K. A. & Frid, M. G. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ. Res. 99, 675–691 (2006).
pubmed: 17008597 doi: 10.1161/01.RES.0000243584.45145.3f
Richalet, J.-P. & Pichon, A. in The Right Heart (eds. Gaine, S. P., Naeije, R. & Peacock, A. J.) 117–129 (Springer, 2014). 
Naeije, R. et al. Pulmonary artery pressure limits exercise capacity at high altitude. Eur. Respir. J. 36, 1049–1055 (2010).
pubmed: 20378601 doi: 10.1183/09031936.00024410
Hildebrandt, W., Ottenbacher, A., Schuster, M., Swenson, E. R. & Bärtsch, P. Diuretic effect of hypoxia, hypocapnia, and hyperpnea in humans: relation to hormones and O
pubmed: 10658028 doi: 10.1152/jappl.2000.88.2.599
Olsen, N. V. et al. Effects of acute hypoxia on renal and endocrine function at rest and during graded exercise in hydrated subjects. J. Appl. Physiol. 73, 2036–2043 (1992).
pubmed: 1474083 doi: 10.1152/jappl.1992.73.5.2036
Steele, A. R. et al. Global REACH 2018: renal oxygen delivery is maintained during early acclimatization to 4,330 m. Am. J. Physiol. Renal Physiol. 319, F1081–F1089 (2020).
pubmed: 32996319 doi: 10.1152/ajprenal.00372.2020
Singh, M. V. et al. Blood gases, hematology, and renal blood flow during prolonged mountain sojourns at 3500 and 5800 m. Aviat. Space Environ. Med. 74, 533–536 (2003).
pubmed: 12751582
Richalet, J. P. et al. Control of erythropoiesis in humans during prolonged exposure to the altitude of 6,542 m. Am. J. Physiol. 266, R756–R764 (1994).
pubmed: 8160868
Lozano, R. & Monge, C. Renal function in high-altitude natives and in natives with chronic mountain sickness. J. Appl. Physiol. 20, 1026–1027 (1965).
pubmed: 5837586 doi: 10.1152/jappl.1965.20.5.1026
Ainslie, P. N. & Subudhi, A. W. Cerebral blood flow at high altitude. High Alt. Med. Biol. 15, 133–140 (2014).
pubmed: 24971767 doi: 10.1089/ham.2013.1138
Ter Minassian, A. et al. Doppler study of middle cerebral artery blood flow velocity and cerebral autoregulation during a simulated ascent of Mount Everest. Wilderness Environ. Med. 12, 175–183 (2001).
pubmed: 11562016 doi: 10.1580/1080-6032(2001)012[0175:DSOMCA]2.0.CO;2
Hanada, A., Sander, M. & González-Alonso, J. Human skeletal muscle sympathetic nerve activity, heart rate and limb haemodynamics with reduced blood oxygenation and exercise. J. Physiol. 551, 635–647 (2003).
pubmed: 12909683 pmcid: 2343217 doi: 10.1113/jphysiol.2003.044024
Casey, D. P. et al. Nitric oxide contributes to the augmented vasodilatation during hypoxic exercise. J. Physiol. 588, 373–385 (2010).
pubmed: 19948661 doi: 10.1113/jphysiol.2009.180489
Wilkins, B. W. et al. Exercise intensity-dependent contribution of β-adrenergic receptor-mediated vasodilatation in hypoxic humans. J. Physiol. 586, 1195–1205 (2008).
pubmed: 18048452 doi: 10.1113/jphysiol.2007.144113
Pohl, U. & Busse, R. Hypoxia stimulates release of endothelium-derived relaxant factor. Am. J. Physiol. Heart Circ. Physiol. 256, H1595–H1600 (1989).
doi: 10.1152/ajpheart.1989.256.6.H1595
Kooijman, M. et al. Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans: FMD in the SFA is nitric oxide mediated. J. Physiol. 586, 1137–1145 (2008).
pubmed: 18096601 doi: 10.1113/jphysiol.2007.145722
Mortensen, S. P., Nyberg, M., Thaning, P., Saltin, B. & Hellsten, Y. Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation. Hypertension 53, 993–999 (2009).
pubmed: 19433775 doi: 10.1161/HYPERTENSIONAHA.109.130880
Azad, P. et al. High-altitude adaptation in humans: from genomics to integrative physiology. J. Mol. Med. 95, 1269–1282 (2017).
pubmed: 28951950 doi: 10.1007/s00109-017-1584-7
Moore, L. G., Armaza, F., Villena, M. & Vargas, E. Comparative aspects of high-altitude adaptation in human populations. Adv. Exp. Med. Biol. 475, 45–62 (2000).
pubmed: 10849648 doi: 10.1007/0-306-46825-5_6
Hunley, K., Gwin, K. & Liberman, B. A Reassessment of the impact of European contact on the structure of Native American genetic diversity. PLoS ONE 11, e0161018 (2016).
pubmed: 27579784 pmcid: 5007009 doi: 10.1371/journal.pone.0161018
Hultgren, H. N. & Miller, H. Human heart weight at high altitude. Circulation 35, 207–218 (1967).
pubmed: 4224830 doi: 10.1161/01.CIR.35.1.207
Antezana, A. et al. Pulmonary hypertension in high-altitude chronic hypoxia: response to nifedipine. Eur. Respir. J.  12, 1181–1185 (1998).
pubmed: 9864018 doi: 10.1183/09031936.98.12051181
León-Velarde, F., Villafuerte, F. C. & Richalet, J.-P. Chronic mountain sickness and the heart. Prog. Cardiovasc. Dis. 52, 540–549 (2010).
pubmed: 20417348 doi: 10.1016/j.pcad.2010.02.012
Maignan, M. et al. Pulmonary pressure and cardiac function in chronic mountain sickness patients. Chest 135, 499–504 (2009).
doi: 10.1378/chest.08-1094
Corante, N. et al. Excessive erythrocytosis and cardiovascular risk in Andean highlanders. High Alt. Med. Biol. 19, 221–231 (2018).
pubmed: 29782186 pmcid: 6157350 doi: 10.1089/ham.2017.0123
Pratali, L. et al. RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness. JACC Cardiovasc. Imag. 6, 1287–1297 (2013).
doi: 10.1016/j.jcmg.2013.08.007
Severinghaus, J. W., Bainton, C. R. & Carcelen, A. Respiratory insensitivity to hypoxia in chronically hypoxic man. Respir. Physiol. 1, 308–334 (1966).
pubmed: 5968347 doi: 10.1016/0034-5687(66)90049-1
Antezana, A., Richalet, J., Antezana, G., Spielvogel, H. & Kacimi, R. Adrenergic aystem in high altitude residents. Int. J. Sports Med.  13, S96–S100 (1992).
pubmed: 1336484 doi: 10.1055/s-2007-1024608
Richalet, J.-P. et al. Acetazolamide for Monge’s disease: efficiency and tolerance of 6-month treatment. Am. J. Respir. Crit. Care Med.  177, 1370–1376 (2008).
pubmed: 18388356 doi: 10.1164/rccm.200802-196OC
Aryal, N., Weatherall, M., Bhatta, Y. K. D. & Mann, S. Blood pressure and hypertension in adults permanently living at high altitude: a systematic review and meta-analysis. High Alt. Med. Biol. 17, 185–193 (2016).
pubmed: 27575245 doi: 10.1089/ham.2015.0118
Sun, S. Epidemiology of hypertension on the Tibetan plateau. Hum. Biol. 58, 507–515 (1986).
pubmed: 3759052
Hancco, I. et al. Excessive erythrocytosis and chronic mountain sickness in dwellers of the highest city in the world. Front. Physiol. 11, 773 (2020).
pubmed: 32760289 pmcid: 7373800 doi: 10.3389/fphys.2020.00773
Coombs, G. B. et al. Global Reach 2018: nitric oxide-mediated cutaneous vasodilation is reduced in chronic, but not acute, hypoxia independently of enzymatic superoxide formation. Free Radic. Biol. Med. 172, 451–458 (2021).
pubmed: 34129928 doi: 10.1016/j.freeradbiomed.2021.06.005
Beall, C. M., Laskowski, D. & Erzurum, S. C. Nitric oxide in adaptation to altitude. Free Radic. Biol. Med. 52, 1123–1134 (2012).
pubmed: 22300645 pmcid: 3295887 doi: 10.1016/j.freeradbiomed.2011.12.028
Tremblay, J. C. et al. Global Reach 2018: high blood viscosity and hemoglobin concentration contribute to reduced flow-mediated dilation in high-altitude excessive erythrocytosis. Hypertension 73, 1327–1335 (2019).
pubmed: 31006327 doi: 10.1161/HYPERTENSIONAHA.119.12780
Basak, N. & Thangaraj, K. High-altitude adaptation: role of genetic and epigenetic factors. J. Biosci. 46, 107 (2021).
pubmed: 34840149 doi: 10.1007/s12038-021-00228-5
Beall, C. M. Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integr. Comp. Biol. 46, 18–24 (2006).
pubmed: 21672719 doi: 10.1093/icb/icj004
Beall, C. M. et al. Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc. Natl Acad. Sci. USA 107, 11459–11464 (2010).
pubmed: 20534544 pmcid: 2895075 doi: 10.1073/pnas.1002443107
Bigham, A. et al. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Genet. 6, e1001116 (2010).
pubmed: 20838600 pmcid: 2936536 doi: 10.1371/journal.pgen.1001116
Simonson, T. S. et al. Genetic evidence for high-altitude adaptation in Tibet. Science 329, 72–75 (2010).
pubmed: 20466884 doi: 10.1126/science.1189406
Sharma, V., Varshney, R. & Sethy, N. K. Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures. Hum. Genomics 16, 21 (2022).
pubmed: 35841113 pmcid: 9287971 doi: 10.1186/s40246-022-00395-y
Scheinfeldt, L. B. et al. Genetic adaptation to high altitude in the Ethiopian highlands. Genome Biol. 13, R1 (2012).
pubmed: 22264333 pmcid: 3334582 doi: 10.1186/gb-2012-13-1-r1
Espinoza, J. R. et al. Vascular endothelial growth factor-A is associated with chronic mountain sickness in the Andean population. High Alt. Med. Biol. 15, 146–154 (2014).
pubmed: 24971768 pmcid: 4074753 doi: 10.1089/ham.2013.1121
Gazal, S. et al. The genetic architecture of chronic mountain sickness in Peru. Front. Genet. 10, 690 (2019).
pubmed: 31417607 pmcid: 6682665 doi: 10.3389/fgene.2019.00690
Zhou, D. et al. Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders. Am. J. Hum. Genet. 93, 452–462 (2013).
pubmed: 23954164 pmcid: 3769925 doi: 10.1016/j.ajhg.2013.07.011
Ravenhill, T. H. Some experiences of mountain sickness in the Andes. J. Trop. Med. Hyg. 16, 313–320 (1913).
Houston, C. S. Acute pulmonary edema of high altitude. N. Engl. J. Med. 263, 478–480 (1960).
pubmed: 14403413 doi: 10.1056/NEJM196009082631003
Richalet, J.-P., Jeny, F., Callard, P. & Bernaudin, J.-F. High altitude pulmonary edema: the intercellular network hypothesis. Am. J. Physiol. Lung Cell. Mol. Physiol. https://doi.org/10.1152/ajplung.00292.2022 (2023).
Donegani, E. et al. Pre-existing cardiovascular conditions and high altitude travel.Travel Med. Infect. Dis. 12, 237–252 (2014).
pubmed: 24675141 doi: 10.1016/j.tmaid.2014.02.004
Luks, A. M. & Hackett, P. H. Medical conditions and high-altitude travel. N. Engl. J. Med. 386, 364–373 (2022).
pubmed: 35081281 doi: 10.1056/NEJMra2104829
Parati, G. et al. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: a joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine. Eur. Heart J. 39, 1546–1554 (2018).
pubmed: 29340578 pmcid: 5930248 doi: 10.1093/eurheartj/ehx720
Mollard, P. et al. Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance athletes. Eur. J. Appl. Physiol. 100, 663–673 (2007).
pubmed: 17534646 doi: 10.1007/s00421-007-0457-0
Schmid, J.-P. Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease. Heart 92, 921–925 (2006).
pubmed: 16339809 doi: 10.1136/hrt.2005.072520
de Vries, S. T. et al. Impact of high altitude on echocardiographically determined cardiac morphology and function in patients with coronary artery disease and healthy controls. Eur. J. Echocardiogr. 11, 446–450 (2010).
pubmed: 20139441 doi: 10.1093/ejechocard/jep237
Morgan, B. J., Alexander, J. K., Nicoli, S. A. & Brammell, H. L. The patient with coronary heart disease at altitude: observations during acute exposure to 3100 meters. J. Wilderness Med. 1, 147–153 (1990).
doi: 10.1580/0953-9859-1.3.147
Salvi, P. et al. Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide. Hypertension 61, 793–799 (2013).
pubmed: 23438935 doi: 10.1161/HYPERTENSIONAHA.111.00707
Agostoni, P. et al. Effects of simulated altitude-induced hypoxia on exercise capacity in patients with chronic heart failure. Am. J. Med. 109, 450–455 (2000).
pubmed: 11042233 doi: 10.1016/S0002-9343(00)00532-5
Schmid, J.-P. et al. Short-term high altitude exposure at 3454 m is well tolerated in patients with stable heart failure. Eur. J. Heart Fail. 17, 182–186 (2015).
pubmed: 25597947 doi: 10.1002/ejhf.227
Vona, M. et al. Effects of altitude on effort tolerance in non-acclimatized patients with ischemic left ventricular dysfunction. Eur. J. Cardiovasc. Prev. Rehabil. 13, 617–624 (2006).
pubmed: 16874154 doi: 10.1097/01.hjr.0000220583.27140.9b
Staempfli, R. et al. Cardiopulmonary adaptation to short-term high altitude exposure in adult Fontan patients. Heart 102, 1296–1301 (2016).
pubmed: 27217067 doi: 10.1136/heartjnl-2016-309682
Allemann, Y. et al. Patent foramen ovale and high-altitude pulmonary edema. JAMA 296, 2954–2958 (2006).
pubmed: 17190896 doi: 10.1001/jama.296.24.2954
Bilo, G. et al. Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study. Hypertension 65, 1266–1272 (2015).
pubmed: 25895588 doi: 10.1161/HYPERTENSIONAHA.114.05003
Wu, T.-Y. et al. Who should not go high: chronic disease and work at altitude during construction of the Qinghai-Tibet railroad. High Alt. Med. Biol. 8, 88–107 (2007).
pubmed: 17584003 doi: 10.1089/ham.2007.1015
Hackett, P. H. et al. High-altitude pulmonary edema in persons without the right pulmonary artery. N. Engl. J. Med. 302, 1070–1073 (1980).
pubmed: 7366625 doi: 10.1056/NEJM198005083021907
Richalet, J.-P., Chenivesse, C., Larmignat, P. & Meille, L. High altitude pulmonary edema, Down syndrome, and obstructive sleep apneas. High Alt. Med. Biol. 9, 179–181 (2008).
pubmed: 18578649 doi: 10.1089/ham.2007.1062
Lichtblau, M. et al. Altitude travel in patients with pulmonary hypertension: randomized pilot-trial evaluating nocturnal oxygen therapy. Front. Med. 7, 502 (2020).
doi: 10.3389/fmed.2020.00502
Verges, S., Chacaroun, S., Godin-Ribuot, D. & Baillieul, S. Hypoxic conditioning as a new therapeutic modality. Front. Pediatr. 3, 58 (2015).
pubmed: 26157787 pmcid: 4476260 doi: 10.3389/fped.2015.00058
Burtscher, J., Mallet, R. T., Burtscher, M. & Millet, G. P. Hypoxia and brain aging: neurodegeneration or neuroprotection? Ageing Res. Rev. 68, 101343 (2021).
pubmed: 33862277 doi: 10.1016/j.arr.2021.101343
Moncayo, J., de Freitas, G. R., Bogousslavsky, J., Altieri, M. & van Melle, G. Do transient ischemic attacks have a neuroprotective effect? Neurology 54, 2089–2094 (2000).
pubmed: 10851368 doi: 10.1212/WNL.54.11.2089
Zhang, Y. et al. Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro. Brain Res. 1725, 146432 (2019).
pubmed: 31491422 doi: 10.1016/j.brainres.2019.146432
Serebrovskaya, T. V., Manukhina, E. B., Smith, M. L., Downey, H. F. & Mallet, R. T. Intermittent hypoxia: cause of or therapy for systemic hypertension? Exp. Biol. Med. 233, 627–650 (2008).
doi: 10.3181/0710-MR-267
Mateika, J. H. & Syed, Z. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations. Respir. Physiol. Neurobiol. 188, 289–300 (2013).
pubmed: 23587570 pmcid: 3775908 doi: 10.1016/j.resp.2013.04.010
Hobbins, L., Hunter, S., Gaoua, N. & Girard, O. Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review. Am. J. Physiol. Regul. Integr. Comp. Physiol. 313, R251–R264 (2017).
pubmed: 28679682 doi: 10.1152/ajpregu.00160.2017
Klug, L. et al. Normobaric hypoxic conditioning in men with metabolic syndrome. Physiol. Rep. 6, e13949 (2018).
pubmed: 30565412 pmcid: 6299242 doi: 10.14814/phy2.13949
Burtscher, M. Lower mortality rates in those living at moderate altitude. Aging 8, 2603–2604 (2016).
pubmed: 27705903 pmcid: 5115909 doi: 10.18632/aging.101057
Ezzati, M. et al. Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties. J. Epidemiol. Community Health 66, e17 (2012).
pubmed: 21406589 doi: 10.1136/jech.2010.112938
Faeh, D., Gutzwiller, F. & Bopp, M. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation 120, 495–501 (2009).
pubmed: 19635973 doi: 10.1161/CIRCULATIONAHA.108.819250
Lopez-Pascual, A., Arévalo, J., Martínez, J. A. & González-Muniesa, P. Inverse association between metabolic syndrome and altitude: a cross-sectional study in an adult population of Ecuador. Front. Endocrinol. 9, 658 (2018).
doi: 10.3389/fendo.2018.00658
Woolcott, O. O. et al. Inverse association between diabetes and altitude: a cross-sectional study in the adult population of the United States: diabetes at high altitude. Obesity 22, 2080–2090 (2014).
pubmed: 24890677 doi: 10.1002/oby.20800
Coté, T. R., Stroup, D. F., Dwyer, D. M., Horan, J. M. & Peterson, D. E. Chronic obstructive pulmonary disease mortality: a role for altitude. Chest 103, 1194–1197 (1993).
pubmed: 8131464 doi: 10.1378/chest.103.4.1194
Anderson, J. D. & Honigman, B. The effect of altitude-induced hypoxia on heart disease: do acute, intermittent, and chronic exposures provide cardioprotection? High Alt. Med. Biol. 12, 45–55 (2011).
pubmed: 21452965 doi: 10.1089/ham.2010.1021
Sanchis-Gomar, F., Viña, J. & Lippi, G. Intermittent hypobaric hypoxia applicability in myocardial infarction prevention and recovery. J. Cell Mol. Med. 16, 1150–1154 (2012).
pubmed: 22151473 pmcid: 4365893 doi: 10.1111/j.1582-4934.2011.01508.x
del Pilar Valle, M. et al. Improvement of myocardial perfusion in coronary patients after intermittent hypobaric hypoxia. J. Nucl. Cardiol. 13, 69–74 (2006).
pubmed: 16464719 doi: 10.1016/j.nuclcard.2005.11.008
Burtscher, M. et al. Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int. J. Cardiol. 96, 247–254 (2004).
pubmed: 15262041 doi: 10.1016/j.ijcard.2003.07.021
Saeed, O. et al. Improved exercise performance and skeletal muscle strength after simulated altitude exposure: a novel approach for patients with chronic heart failure. J. Card. Fail. 18, 387–391 (2012).
pubmed: 22555269 doi: 10.1016/j.cardfail.2012.02.003
Cai, Z. et al. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1. Cardiovasc. Res. 77, 463–470 (2007).
pubmed: 18006459 doi: 10.1093/cvr/cvm035
Huang, T. et al. Hypoxia-inducible factor-1α upregulation in microglia following hypoxia protects against ischemia-induced cerebral infarction. NeuroReport 25, 1122–1128 (2014).
pubmed: 25089804 doi: 10.1097/WNR.0000000000000236
Belaidi, E., Beguin, P. C., Levy, P., Ribuot, C. & Godin-Ribuot, D. Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium results in loss of myocardial hypoxic preconditioning in the rat. Am. J. Physiol. Heart Circ. Physiol. 294, H901–H908 (2008).
pubmed: 18083903 doi: 10.1152/ajpheart.00715.2007
Park, A.-M., Nagase, H., Vinod Kumar, S. & Suzuki, Y. J. Acute intermittent hypoxia activates myocardial cell survival signaling. Am. J. Physiol. Heart Circ. Physiol. 292, H751–H757 (2007).
pubmed: 17098826 doi: 10.1152/ajpheart.01016.2006
Joyeux-Faure, M., Godin-Ribuot, D. & Ribuot, C. Erythropoietin and myocardial protection: what’s new? Fundam. Clin. Pharmacol. 19, 439–446 (2005).
pubmed: 16011730 doi: 10.1111/j.1472-8206.2005.00347.x
Moore, E. & Bellomo, R. Erythropoietin (EPO) in acute kidney injury. Ann. Intensive Care 1, 3 (2011).
pubmed: 21906325 pmcid: 3159901 doi: 10.1186/2110-5820-1-3
El’chaninova, S. A., Korenyak, N. A., Pavlovskaya, L. I., Smagina, I. V. & Makarenko, V. V. The effect of interval hypoxic hypoxia on the vascular endothelial growth factor and basic fibroblast growth factor concentrations in the peripheral blood. Hum. Physiol. 30, 705–707 (2004).
doi: 10.1023/B:HUMP.0000049591.78738.55
Maulik, N. & Das, D. K. Redox signaling in vascular angiogenesis. Free Radic. Biol. Med. 33, 1047–1060 (2002).
pubmed: 12374616 doi: 10.1016/S0891-5849(02)01005-5
Ray, P. S., Estrada-Hernandez, T., Sasaki, H., Zhu, L. & Maulik, N. Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. Mol. Cell Biochem. 213, 145–153 (2000).
pubmed: 11129953 doi: 10.1023/A:1007180518474
Dempsey, J. A., Veasey, S. C., Morgan, B. J. & O’Donnell, C. P. Pathophysiology of sleep apnea. Physiol. Rev. 90, 47–112 (2010).
pubmed: 20086074 pmcid: 3970937 doi: 10.1152/physrev.00043.2008
Mallet, R. T., Manukhina, E. B., Ruelas, S. S., Caffrey, J. L. & Downey, H. F. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential. Am. J. Physiol. Heart Circ. Physiol. 315, H216–H232 (2018).
pubmed: 29652543 pmcid: 6139623 doi: 10.1152/ajpheart.00060.2018
Navarrete-Opazo, A. & Mitchell, G. S. Therapeutic potential of intermittent hypoxia: a matter of dose. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R1181–R1197 (2014).
pubmed: 25231353 pmcid: 4315448 doi: 10.1152/ajpregu.00208.2014
Millet, G. P. et al. Commentaries on viewpoint: time for a new metric for hypoxic dose? J. Appl. Physiol. 121, 356–358 (2016).
pubmed: 27451276 doi: 10.1152/japplphysiol.00460.2016
Richalet, J.-P. Oxygen sensors in the organism: examples of regulation under altitude hypoxia in mammals. Comp. Biochem. Physiol. A Physiol. 118, 9–14 (1997).
pubmed: 9243810 doi: 10.1016/S0300-9629(96)00370-2
Kanai, M., Nishihara, F., Shiga, T., Shimada, H. & Saito, S. Alterations in autonomic nervous control of heart rate among tourists at 2700 and 3700 m above sea level. Wilderness Environ. Med. 12, 8–12 (2001).
pubmed: 11294561 doi: 10.1580/1080-6032(2001)012[0008:AIANCO]2.0.CO;2
Heistad, D. D. & Abboud, F. M. Dickinson W. Richards lecture: circulatory adjustments to hypoxia. Circulation 61, 463–470 (1980).
pubmed: 7353235 doi: 10.1161/01.CIR.61.3.463
Mortensen, S. P., González-Alonso, J., Damsgaard, R., Saltin, B. & Hellsten, Y. Inhibition of nitric oxide and prostaglandins, but not endothelial-derived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg: effect of triple blockade on exercise hyperaemia. J. Physiol. 581, 853–861 (2007).
pubmed: 17347273 pmcid: 2075180 doi: 10.1113/jphysiol.2006.127423
Richalet, J.-P. & Herry, J.-P. Médecine de Montagne: Alpinisme et Sports de Montagne 5th edn, Vol. 72 (Elsevier Masson, 2017).

Auteurs

Jean-Paul Richalet (JP)

Hypoxie et Poumon, Université Sorbonne Paris Nord, INSERM U1272, Paris, France. richalet@univ-paris13.fr.

Eric Hermand (E)

Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR 7369-URePSSS, Université Littoral Côte d'Opale, Université Artois, Université Lille, CHU Lille, Dunkirk, France.

François J Lhuissier (FJ)

Hypoxie et Poumon, Université Sorbonne Paris Nord, INSERM U1272, Paris, France.

Classifications MeSH