Advertisement

Hypoxia pp 89-106 | Cite as

Update: High altitude pulmonary edema

  • Peter Bärtsch
  • Erik R. Swenson
  • Marco Maggiorini
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 502)

Abstract

Recent high altitude studies with pulmonary artery (PA) catheterization and broncho-alveolar lavage (BAL) in early high altitude pulmonary edema(HAPE) have increased our understanding of the pathogenetic sequence in HAPE. High preceding PA and pulmonary capillary pressures lead to a noninflammatory leak of the alveolar-capillary barrier with egress of red cells, plasma proteins and fluid into the alveolar space. The mechanisms accounting for an increased capillary pressure remain speculative. The concept that hypoxic pulmonary vasoconstriction (HPV) is uneven so that regions with less vasoconstriction are over-perfused and become edematous remains compelling but unproved. Also uncertain is the role and extent of pulmonary venoconstriction. With disruption of the normal alveolar-capillary barrier, some individuals may later develop a secondary inflammatory reaction. A high incidence of preceding or concurrent respiratory infection in children with HAPE has been used to support a causative role of inflammation in HAPE. However, alternatively even mild HPV may simply lower the threshold at which inflammation-mediated increases in alveolar capillary permeability cause significant fluid flux into the lung. Other major questions to be addressed in future research are: 1.) What is the mechanism of exaggerated hypoxic pulmonary vasoconstriction? Is there a link to primary pulmonary hypertension? Several observations suggest that susceptibility to HAPE is associated with endothelial dysfunction in pulmonary vessels. This has not yet been studied adequately. 2.) What is the nature of the leak? Is there structural damage, i. e. stress failure, or does stretch cause opening of pores? 3.) What is the pathophysiologic significance of a decreased sodium and water clearance across alveolar epithelial cells in hypoxia? 4.) What is the role of exercise? Do HAPE-susceptible individuals develop pulmonary edema when exposed to hypoxia without exercise? Answers to these questions will increase our understanding of the pathophysiology of HAPE and also better focus research on the genetic basis of susceptibility to HAPE.

Keywords

goals for research pathophysiology inflammation hydrostatic edema capillary pressure 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Audi SH, Dawson DA, Rickaby A, and Linehan JH. Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion. J Appl Physiol 70: 2126–2136, 1991.PubMedGoogle Scholar
  2. 2.
    Barman SH and Pauly JR. Mechanism of action of endothelin-1 in the canine pulmonary circulation. J Appl Physiol 79: 2014–2020, 1995.PubMedGoogle Scholar
  3. 3.
    Bartsch P. High altitude pulmonary edema. Med Sci Sports Exerc 31: S23–S27, 1999.PubMedCrossRefGoogle Scholar
  4. 4.
    Bartsch P, Eichenberger U, Ballmer PE, Gibbs JSR, Schirlo C, Oelz O, and Mayatepek E. Urinary leukotriene E4 levels are not increased prior to high-altitude pulmonary edema. Chest 117: 1393–1398, 2000.PubMedCrossRefGoogle Scholar
  5. 5.
    Bartsch P, Haeberli A, Franciolli M, Kruithof EKO, and Straub PW. Coagulation and fibrinolysis in acute mountain sickness and beginning pulmonary edema. J Appl Physiol: 66:2136–2144, 1989.PubMedGoogle Scholar
  6. 6.
    Bartsch P, Haeberli A, Nanzer A, et al. High altitude pulmonary edema: Blood coagulation. In: Sutton JR, Houston CS, and Coates G (eds.), Hypoxia and molecular medicine. Burlington: Queen City Printers Inc, 1993, pp. 252–258.Google Scholar
  7. 7.
    Bärtsch P, Maggiorini M, Ritter M, Noti C, Vock P, and Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med: 325:1284–1289, 1991.PubMedCrossRefGoogle Scholar
  8. 8.
    Busch T, Bartsch P, Pappert D, Grünig E, Elser H, Falke KJ, and Swenson ER. Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high altitude pulmonary edema. Am J Respir Cht Care Med 163: 368–373, 2001.Google Scholar
  9. 9.
    Drake RE, Smith JH, and Gabel JC. Estimation of the filtration coefficient in intact dog lungs. Am J Physiol 238: H430–H438, 1980.PubMedGoogle Scholar
  10. 10.
    Duplain H, Sartori C, Lepori M, Egli M, Allemann Y, Nicod P, and Scherrer U. Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation. Am J Resp Crit Care Med 162:221–224, 2000.PubMedGoogle Scholar
  11. 11.
    Duplain H, Vollenweider L, Delabays A, Nicod P, Bärtsch P, and Scherrer U. Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema. Circulation 99: 1713–1718, 1999.PubMedCrossRefGoogle Scholar
  12. 12.
    Durmowicz AG, Nooordeweir E, Nicholas R, and Reeves JT. Inflammatory processes may predispose children to develop high altitude pulmonary edema. J Pediatr 130: 838–840, 1997.PubMedCrossRefGoogle Scholar
  13. 13.
    Eldridge MW, Podolsky A, Richardson RS, Johnson DH, Knight DR, Johnson EC, Hopkins SR, Michimata H, et al. Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pumonary edema. J Appl Physiol 81: 911–921, 1996.PubMedGoogle Scholar
  14. 14.
    Frank JA, Wang Y, Osorio O, and Mathhay MA. β-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J Appl Physiol S9: 1255–1265,2000.Google Scholar
  15. 15.
    Fullerton DA, Agrafojo J, and Mclntyre Jr. RC. Pulmonary vascular smooth muscle relaxation by cAMP-mediated pathways. J Surg Res 61: 444–448, 1996.PubMedCrossRefGoogle Scholar
  16. 16.
    Gilbert E, Hakim TS. Derivation of pulmonary capillary pressure from arterial acclusion in intact conditions. Crit Care Med 22: 986–993, 1994.PubMedCrossRefGoogle Scholar
  17. 17.
    Grünig E, Janssen B, Mereles D, Barth U, Borst M, Vogt IR, Fischer C, Olschewski H, Kuecherer HF, and Kubier W. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation 102: 1145–1150, 2000.PubMedCrossRefGoogle Scholar
  18. 18.
    Grünig E, Mereles D, Hildebrandt W, Swenson ER, Kübier W, Kuecherer H, and Bärtsch P. Stress doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol 35: 980–987, 2000.PubMedCrossRefGoogle Scholar
  19. 19.
    Hackett PH, Roach RC, Hartig GS, Greene ER, and Levine BD. The effect of vasodilatators on pulmonary hemodynamics in high altitude pulmonary edema: A comparison. Int J Sports Med 13: S68–S71, 1992.PubMedCrossRefGoogle Scholar
  20. 20.
    Hakim TS. Identification of constriction in large vs. small vessels using the arterial-venous and double-occlusion technique in isolated canine lungs. Respir 54: 61–69, 1988.CrossRefGoogle Scholar
  21. 21.
    Hakim TS and Kelly S. Occlusion pressures vs. micropipette pressures in the pulmonary circulation. J Appl Physiol 67: 1277–1285, 1989.PubMedGoogle Scholar
  22. 22.
    Hakim TS, Sugimori K, Camporesi EM, and Anderson G. Half-life of nitric oxide in aqueous solutions with and without haemoglobin. Physiol Meas 17: 267–277, 1996.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanaoka M, Kubo K, Yamazaki Y, Miyahara T, Matsuzawa Y, Kobayashi T, Sekiguchi M, Ota M, and Watanabe H. Association of high-altitude pulmonary edema with the major histocompatibility complex. Circulation 97: 1124–1128, 1998.PubMedCrossRefGoogle Scholar
  24. 24.
    Hillier SC, Graham JA, Hanger CC, Godbey PS, Glenny RW, and Wagner Jr. WW. Hypoxic vasoconstriction in pulmonary arterioles and venules. J Appl Physiol 82: 1084–1090, 1997.PubMedGoogle Scholar
  25. 25.
    Hochstrasser J, Nanzer A, and Oelz O. Das Höhenödem in den Schweizer Alpen. Beobachtungen über Inzidenz, Klinik und Verlauf bei 50 Patienten der Jahre 1980–1984. Schweiz Med Wochenschr 116: 866–873, 1986.PubMedGoogle Scholar
  26. 26.
    Homik LA, Bshouty RB, Light RB, and Younes M. J Appl Physiol 65: 46–52, 1988.PubMedGoogle Scholar
  27. 27.
    Hultgren HN, Grover RF, and Hartley LH. Abnormal circulatory responses to high altitude in subjects with a previous history of high-altitude pulmonary edema. Circulation 44: 759–770, 1971.PubMedCrossRefGoogle Scholar
  28. 28.
    Hultgren NH. High altitude pulmonary edema. Lung Water and Solute Exchange: 237–269, 1978.Google Scholar
  29. 29.
    Kaminsky DA, Jones K, Schoene RB, and Voelkel NF. Urinary leuktriene E4 levels in high-altitude pulmonary edema: A possible role for inflammation. Chest 110: 939–945, 1996.PubMedCrossRefGoogle Scholar
  30. 30.
    Kleger G-R, Bärtsch P, Vock P, Heilig B, Roberts LJI, and Ballmer PE. Evidence against an increase of capillary permeability in subjects exposed to high altitude. J Appl Physiol 81: 1917–1923, 1996.PubMedGoogle Scholar
  31. 31.
    Kubo K, Hanaoka M, Hayano T, Miyahara T, Hachiya T, Hayasaka M, Koizumi T, Fujimoto K, Kobayashi T, and Honda T. Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema. Respir Physiol 111: 301–310, 1997.CrossRefGoogle Scholar
  32. 32.
    Kubo K, Hanaoka M, Yamaguchi S, Hayano T, Hayasaka M, Koizumi T, Fujimoto K, Kobayashi T, and Honda T. Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan. Thorax 51: 739–742, 1996.PubMedCrossRefGoogle Scholar
  33. 33.
    Litch JA and Bishop RA. Reascent following resolution of high altitude pulmonary edema (HAPE) (Case Report). High Alt Med Biol 2: 53–55, 2001.PubMedCrossRefGoogle Scholar
  34. 34.
    Maggiorini M, Mélot C, Pierre S, Pfeiffer F, Greve I, Sartori C, Lepori M, Hauser M, Scherrer U, ND Naeije R. High altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 103:2078–2083, 2001.PubMedCrossRefGoogle Scholar
  35. 35.
    Mitzner W and Sylvester JT. Hypoxic vasoconstriction and fluid filtration in pig lungs. J Appl Physiol 51: 1065–1071, 1981.PubMedGoogle Scholar
  36. 36.
    Oelz O, Ritter M, Jenni R, Maggiorini M, Waber U, Vock P, and Bärtsch P. Nifedipine for High Altitude Pulmonary Oedema. Lancet 2: 1241–1244, 1989.PubMedCrossRefGoogle Scholar
  37. 37.
    Parker JC and Ivey CL. Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs. J Appl Physiol 83: 1962–1967, 1997.PubMedGoogle Scholar
  38. 38.
    Raj JU and Chen P. Micropuncture measurement of microvascular pressures in isolated lamb lungs during hypoxia. Circ Res 59: 398–404, 1986.PubMedCrossRefGoogle Scholar
  39. 39.
    Ritter M, Jenni R, Maggiorini M, Grimm J, and Oelz O. Abnormal left ventricular diastolic filling patterns in acute hypoxic pulmonary hypertension at high altitude. Am J Noninvas Cardiol 7: 33–38, 1993.Google Scholar
  40. 40.
    Roach RC, Maes D, Sandoval D, Robergs RA, Icenogle M, Hinghofer-Szalkay H, Lium D, and Loeppky JA. Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol 88: 581–585, 2000.PubMedGoogle Scholar
  41. 41.
    Rock P, Patterson GA, Permutt S, and Sylvester JT. Nature and distribution of vascular resistance in hypoxic pig lungs. J Appl Physiol 59: 1891–1901, 1985.PubMedGoogle Scholar
  42. 42.
    Roos CM, Rich GF, Uncles DR, Daugherty MO, and Frank DU. Site of vasodilatation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs. J Appl Physiol 11: 51–57, 1994.Google Scholar
  43. 43.
    Sartori C, Lepori M, Busch T, Duplain H, Hildebrandt W, Bärtsch P, Nicod P, Falke KJ, and Scherrer U. Exhaled nitric oxide does not provide a marker of vascular endothelial function in healthy humans. Am J Resp Crit Care Med 160: 879–882, 1999.PubMedGoogle Scholar
  44. 44.
    Sartori C, Vollenweider L, Löffler B-M, Delabays A, Nicod P, Bärtsch P, and Scherrer U. Exaggerated endothelin release in high-altitude pulmonary edema. Circulation 99: 2665–2668, 1999.PubMedCrossRefGoogle Scholar
  45. 45.
    Scherrer U, Vollenweider L, Delabays A, Savcic M, Eichenberger U, Kleger G-R, Firkrle A, Ballmer P, Nicod P, and Bärtsch P. Inhaled nitric oxide for high-altitude pulmonary edema. N Engl J Med 334: 624–629, 1996.PubMedCrossRefGoogle Scholar
  46. 46.
    Schoene RB, Swenson ER, Pizzo CJ, Hackett PH, Roach RC, Mills WJ, Henderson WR, and Martin TR. The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema. J Appl Physiol 64: 2605–2613, 1988.PubMedGoogle Scholar
  47. 47.
    Sugita M, Ferraro P, Yamagata T, Poirier C, and Berthiaume Y. Effects of 3-hour preservation and reperfusion on transalveolar fluid transport mechanism in a canine single lung transplant model (Abstract). Am J Respir Crit Care Med 161: A415, 2000.Google Scholar
  48. 48.
    Swenson ER, Mongovin S, Gibbs S, Maggiorini M, Greve I, Mairbäurl H, and Bärtsch P. Stress failure in high altitude pulmonary edema (HAPE) (abstract). Am J Resp Crit Care Med 161: A418, 2000.Google Scholar
  49. 49.
    Tod ML, O’Donnell DC, and Gordon JB. Sites of inhaled NO-induced vasodilatation during hypoxia and U-46619 infusion in isolated lamb lungs. Am J Physiol 268: H1422-H1427, 1995.PubMedGoogle Scholar
  50. 50.
    Tsukimoto K, Mathieu-Costello O, Prediletto R, Elliott R, and West JB. Ultrastructural appearances of pulmonary capillaries at high transmural pressures. J Appl Physiol 71: 573–582, 1991.PubMedGoogle Scholar
  51. 51.
    West JB, Colice GL, Lee Y-J, Namba Y, Kurdak SS, Fu Z, Ou L-C, and Mathieu-Costello O. Pathogenesis of high-altitude pulmonary oedema: Direct evidence of stress failure of pulmonary capillaries. Eur RespirJ 8: 523–529, 1995.Google Scholar
  52. 52.
    Whayne Jr. TF, Severinghaus JW. Experimental hypoxic pulmonary edema in the rat. J Appl Physiol 25: 729–732, 1968.PubMedGoogle Scholar
  53. 53.
    Yoshimura K, Tod ML, Pier KG, and Rubin LJ. Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs. J Appl Physiol 66: 929–935. 1989.PubMedGoogle Scholar
  54. 54.
    Yoshiro Y, Suzuki S, Watanuki Y, and Okubo T. Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects. Thorax 50:139–142, 1995.CrossRefGoogle Scholar
  55. 55.
    Zhao Y, Packer CS, and Rhoades RA. Pulmonary vein contracts in response to hypoxia. Am J Physiol 265: L87–L92, 1993.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Peter Bärtsch
    • 1
  • Erik R. Swenson
    • 2
  • Marco Maggiorini
    • 3
  1. 1.Department of Internal Medicine, Division of Sports MedicineUniversity of HeidelbergHeidelbergGermany
  2. 2.Pulmonary and Critical Care Division, Department of MedicineUniversity of WashingtonSeattleUSA
  3. 3.Department Innere MedizinUniversitätsspital ZürichSwitzerland

Personalised recommendations