Experimental Models of Acute Lung Injury

  • P. R. M. Rocco
  • W. A. Zin


The first descriptions of acute respiratory distress syndrome appeared in 1967, when Ashbaugh et al. described 12 patients with acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance, and diffuse infiltrates evident on the chest radiograph [1] . It is not defined by a specific pathogenesis, but reflects the lung’s nonselective response to numerous insults and precipitating factors. Although the term acute respiratory distress syndrome (ARDS) is often used interchangeably with acute lung injury (ALI), by strict criteria ARDS should be reserved for the most severe end of the spectrum (Table 1) [2].


Oleic Acid Lung Injury Acute Lung Injury Acute Respiratory Distress Syndrome Respir Crit 
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  1. 1.
    Ashbaugh DG, Bigelow DB, Petty TL et al (1967) Acute respiratory distress syndrome. Lancet 2: 319–323PubMedCrossRefGoogle Scholar
  2. 2.
    Bernard GR, Artigas A, Bringham KL et al (1994). The American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  3. 3.
    Pepe PE, Potkin RT, Resus DR et al (1982) Clinical predictors of the adult respiratory distress syndrome. Am J Surg 144:124–130PubMedCrossRefGoogle Scholar
  4. 4.
    Fein AM, Lippmann M, Hotzman H et al (1983) The risk factors, incidence, and prognosis of ARDS following septicemia. Chest 83:40–42PubMedCrossRefGoogle Scholar
  5. 5.
    Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: A new hypothesis for pathogenesis of the disease process. Chest 112: 235–243PubMedCrossRefGoogle Scholar
  6. 6.
    Ryan SF (1990) Acute alveolar injury: experimental models. In: Gil J (ed) Models of lung disease. Marcel Dekker, New York, pp 641–733Google Scholar
  7. 7.
    Williwerth BM, Crawford FA, Young WG et al (1967) The role of functional demand on the development of pulmonary lesions during hemorrhagic shock. J Thorac Cardiovasc Surgery 54: 658–665Google Scholar
  8. 8.
    Pomerantz M, Eisman B (1968) Experimental shock lung model. J Trauma 8: 782–787PubMedCrossRefGoogle Scholar
  9. 9.
    Sealy WC (1968) The lung in hemorrhagic shock. J Trauma 8: 774–781PubMedCrossRefGoogle Scholar
  10. 10.
    Cook WA (1968) Experimental shock lung model. J Trauma 8: 793–796PubMedCrossRefGoogle Scholar
  11. 11.
    Murray JF, and Staff of Division of Lung Diseases, National Heart, Lung and Blood Institute (1977). Conference Report-Workshop on mechanisms of acute respiratory failure. Am Rev Respir Dis 115: 1071–1078Google Scholar
  12. 12.
    Windsor ACJ, Mullen PG, Fowler AA (1993) Acute lung injury: What have we learned from animal models. Am J Med Sci 306:111–116PubMedCrossRefGoogle Scholar
  13. 13.
    Flick MR (1986) Mechanisms of acute lung injury: What we have learned from experimental animal models. Crit Care Clin 2: 455–470PubMedGoogle Scholar
  14. 14.
    Staub NC (1971) Steady state transvascular water filtration in unanesthetized sheep. Cir Res 28:135–139Google Scholar
  15. 15.
    Brigham KL, Woolverton WC, Blake LH et al (1974) Increased sheep lung vascular permeability caused by Pseudomonas bacteremia. J Clin Invest 54: 792–804PubMedCrossRefGoogle Scholar
  16. 16.
    Craddock PR, Fehr J, Brigham KL et al (1977) Complement and leukocyte mediated pulmonary dysfunction in hemodialysis. N Engl J Med 296: 769–774PubMedCrossRefGoogle Scholar
  17. 17.
    Hammerschmidt DE, Weaver LJ, Hudson LD et al (1980) Association of complement activation and elevated plasma C5a with adult respiratory distress syndrome. Lancet 1: 947–949PubMedCrossRefGoogle Scholar
  18. 18.
    Till GO, Johnson KJ, Kunkel R (1982) Intravascular activation of complement and ALI: Dependency on neutrophils and toxic oxygen metabolites. J Clin Invest 60: 1126–1135CrossRefGoogle Scholar
  19. 19.
    Henson PM, Larsen GL, Webster RO et al (1982) Pulmonary microvascular alterations and injury induced by complement fragments: Synergistic effect of complement activation, neutrophil sequestrations and prostaglandins. Ann NY Acad Sci 348: 287–300CrossRefGoogle Scholar
  20. 20.
    Hosea S, Brown E, Hammer C et al (1980) Role of complement activation in a model of adult respiratory distress syndrome. J Clin Invest 66: 375–382PubMedCrossRefGoogle Scholar
  21. 21.
    Stevens J, O’Hanley PT, Shapiro J et al (1986) Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 77: 1812–1816PubMedCrossRefGoogle Scholar
  22. 22.
    Rabinovici R, Yah C, Hillegass L et al (1992) Role of complement in endotoxin/platelet activity factor-induced lung injury. J Immunol 149: 1744–1750PubMedGoogle Scholar
  23. 23.
    Dehring DJ, Steinberg SM, Wismar BL et al (1987) Complement depletion in a porcine model of acute respiratory disease. J Trauma 27: 615–626PubMedCrossRefGoogle Scholar
  24. 24.
    Flick MR, Horn JK, Hoellfel JM et al (1986) Reduction in total hemolytic complement activity with Naja haje cobra venom factor does not prevent endotoxin induced lung injury in sheep. Am Rev Respir Dis 133: 62–67PubMedGoogle Scholar
  25. 25.
    Brigham K, Meyrick B (1986) Endotoxin and lung injury. Am Rev Respir Dis 133: 913–927PubMedGoogle Scholar
  26. 26.
    Peterson MP, Huttemeier PC, Zapol WM et al (1982) Tromboxane mediates acute pulmonary hypertension in sheep extracorporeal perfusion. Am J Physiol 243: H471-H479Google Scholar
  27. 27.
    Gnidec AG, Sibbald WJ, Cheung H et al (1988) Ibuprofen reduces the progressive permeability edema in an animal model of hyperdynamic sepsis. J Appl Physiol 65: 1024–1032PubMedGoogle Scholar
  28. 28.
    Byrne K, Carey PD, Sielaff TD et al (1991) Ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury. J Trauma 31: 155–166PubMedGoogle Scholar
  29. 29.
    Garcia JG, Noonan TC, Jubiz W et al (1987) Leukotrienes and the pulmonary microcirculation. Am Rev Respir Dis 136: 161–169.PubMedCrossRefGoogle Scholar
  30. 30.
    Gadaleta D, Davis JM (1994) Pulmonary failure and the production of leukotrienes. J Am Coll Surg 178: 309–319PubMedGoogle Scholar
  31. 31.
    Rabinovici R, Bugelski PJ, Esser KM et al (1993) ARDS-like lung injury produced by endotoxin in platelet-activating factor-primed rats. J Appl Physiol 74: 1791–1802PubMedGoogle Scholar
  32. 32.
    Bachofen A, Weibel ER (1977) Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116: 589–615PubMedGoogle Scholar
  33. 33.
    Meyrick B, Ryan US, Brigham KL (1990) Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep. Lab Invest 62: 355–362PubMedGoogle Scholar
  34. 34.
    Heflin AC, Brigham KL (1981) Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. J Clin Invest 68:1253–1260PubMedCrossRefGoogle Scholar
  35. 35.
    Shasby DM, Vanbenthugsen KM, Tate RM et al (1982) Granulocyte mediated acute edematous lung injury in rabbits and isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals. Am Rev Respir Dis 125: 443–447PubMedGoogle Scholar
  36. 36.
    Brigham KL, Meyrick B, Berry JC et al (1987) Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxin. J Appl Physiol 63:840–850PubMedGoogle Scholar
  37. 37.
    Hinson J, Hutchison A, Ogletree M et al (1983) Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep. J Appl Physiol 55: 92–99PubMedGoogle Scholar
  38. 38.
    Kelley J (1990) Cytokines of the lung. Am Rev Respir Dis 141: 765–788PubMedCrossRefGoogle Scholar
  39. 39.
    Walsh CJ, Sugerman HJ, Mullen PG et al (1992) Monoclonal antibody to tumor necrosis factor ??attenuates cardiopulmonary dysfunction in porcine gram negative sepsis. Arch Surg 127: 138–145PubMedCrossRefGoogle Scholar
  40. 40.
    Mulligan MS, Jones ML, Bolanowski MA et al (1993) J Immunol 150: 5585–5595PubMedGoogle Scholar
  41. 41.
    Sekido N, Mukaida N, Harada A et al (1993) Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 365:654–657PubMedCrossRefGoogle Scholar
  42. 42.
    Wakabayashi G, Gelfand JA, Burke J et al (1991) A specific receptor antagonist for interleukin 1 prevents Escherichia coli induced shock in rabbits. FASEB J 5: 338–343PubMedGoogle Scholar
  43. 43.
    Canonico AE, Brigham KL (1997) Biology of Acute Injury. In Crystal RG, West JB (eds) The Lung. Scientific Foundations. Lippincott-Raven Publishers, Philadelphia, pp 2475–2498Google Scholar
  44. 44.
    Opal SM, DePalo VA (2000) Impact of basic research on tomorrow’s medicine anti-inflammatory cytokines. Chest 117: 1162–1172PubMedCrossRefGoogle Scholar
  45. 45.
    Cassatella MA, Meda L, Bonora S, et al (1993) Interleukin 10 (IL-10) inhibits the release of pro-inflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role for tumor necrosis factor and IL-12 in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med 178: 2207–2211PubMedCrossRefGoogle Scholar
  46. 46.
    Parsons PE (2000) Mediators and mechanisms of acute lung injury. Clin Chest Med 3: 467–476CrossRefGoogle Scholar
  47. 47.
    Pittet JF, MacKersie RC, Martin TR et al (1997) Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155: 1187–1205PubMedGoogle Scholar
  48. 48.
    Dreyfuss D, Soler P, Basset G et al (1988) High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 137: 1159–1164PubMedGoogle Scholar
  49. 49.
    Bowton DL, Kong DL (1989) High tidal volume ventilation produces increased lung water in oleic acid injured rabbit lung. Crit Care Med 17: 908–911PubMedCrossRefGoogle Scholar
  50. 50.
    Snyder JV, Froese A (1987) The open lung approach: concept and application. In: Snyder JV and Pinsky MR (eds) Oxygen Transport in the Critically 111. Year Book Medical Publishers, Chicago, pp 374–395Google Scholar
  51. 51.
    Rotta AR, Steinhorn DM (1998) Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury. Crit Care Med 10: 1707–1715CrossRefGoogle Scholar
  52. 52.
    Doctor A, Price B, Bhargava N et al (2001) High frequency oscillatory ventilation of the perfluorocarbon-filled lung: dose response relationships in an animal model of acute lung injury. Crit Care Med 29: 847–854PubMedCrossRefGoogle Scholar
  53. 53.
    Verbrugge SJC, Uhlig S, Neggers SJCMM et al (1999) Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo. Anesthesiology 91: 1834–1843PubMedCrossRefGoogle Scholar
  54. 54.
    Broccard A, Shapiro RS, Schmitz LL et al (2000) Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs. Crit Care Med 28: 295–303PubMedCrossRefGoogle Scholar
  55. 55.
    Van der Kloot TE, Blanch L, Youngblood M et al (2000) Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange. Am J Respir Crit Care Med 161: 1485–1494PubMedGoogle Scholar
  56. 56.
    Waugh JB, Op’t Holt TB, Olson LE et al (2000) Surfactant treatment impairs gas exchange in a canine model of acute lung injury. Crit Care Med 28: 2887–2892PubMedCrossRefGoogle Scholar
  57. 57.
    Brackenbury AM, Puligandla OS, McCaig LA et al (2001) Evaluation of exogenous surfactant in HCl-induced lung injury. Am J Respir Crit Care Med 163: 1135–1142PubMedGoogle Scholar
  58. 58.
    Delavai PM, Gillespie DJ (1985) Pulmonary dysfunction during paraquat-induced lung injury: A model of acute alveolar injury. Crit Care Med 13:1056–1060CrossRefGoogle Scholar
  59. 59.
    Smith P, Health D, Kay JM (1974) The pathogenesis and structure of paraquat-induced lung fibrosis in rats. J Pathol 114:57–67PubMedCrossRefGoogle Scholar
  60. 60.
    Rocco PRM, Negri EM, Kurtz PM et al (2001) Lung tissue mechanics and extracellular matrix remodeling in acute lung injury. Am J Respir Crit Care Med (in press)Google Scholar
  61. 61.
    Schuster DP (1994) ARDS: Clinical lessons from the oleic acid model of acute lung injury. Am J Respir Crit Care Med 149:245–260PubMedGoogle Scholar
  62. 62.
    Derks CM and Jacobovitz-Derks D (1977) Embolic pneumopathy induced by oleic acid. Am J Pathol 87: 143–158PubMedGoogle Scholar
  63. 63.
    Schoene RB, Robertson HT, Thorning DR et al (1984) Pathophysiological patterns of resolution from acute oleic acid lung injury in the dog. J Appl Physiol 56: 472–481PubMedGoogle Scholar
  64. 64.
    Johanson WG Jr, Holcomb JR, Coalson J (1982) Experimental diffuse alveolar damage in baboons. Am Rev Respir Dis 126: 142–151PubMedGoogle Scholar
  65. 65.
    Furue S, Mikawa K, Nishina K et al (2001). Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection. Crit Care Med 29: 719–727PubMedCrossRefGoogle Scholar
  66. 66.
    Enrione MA, Papo MC, Leach CL, et al (1999) Regional pulmonary blood flow during partial liquid ventilation in normal and acute oleic acid-induced lung injured piglets. Crit Care Med 27: 2716–2723PubMedCrossRefGoogle Scholar
  67. 67.
    Lachmann B, Robertson B, Vogel J (1980) In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesthesiol Scand 24: 231–236PubMedCrossRefGoogle Scholar
  68. 68.
    Brigham K, Bowers R, Haynes J (1979) Increased sheep lung vascular permeability caused by E. coli endotoxin. Circulation 45: 292–297CrossRefGoogle Scholar
  69. 69.
    Van Helden HP, Kuijpers WC, Steenvoorden D et al (1997) Intratracheal aerolization of endotoxin (LPS) in the rat: a comprehensive animal model to study adult (acute) respiratory distress syndrome. Exp Lung Res 23: 297–316PubMedCrossRefGoogle Scholar
  70. 70.
    Rotta AT, Gunnarsson B, Hernan LJ et al (1999) Partial liquid ventilation influences pulmonary histopathology in an animal model of acute lung injury. J Crit Care 14: 84–92PubMedCrossRefGoogle Scholar
  71. 71.
    Faffe DS, Scidl VR, Chagas PSC, Gonçalves de Moraes VL, Capelozzi VL, Rocco PRM, Zin WA (2000) Respiratory effects of lipopolysaccharide-induced inflammatory lung injury in mice. Eur Respir J 15: 85–91PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2002

Authors and Affiliations

  • P. R. M. Rocco
    • 1
  • W. A. Zin
    • 1
  1. 1.Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics InstituteFederal University of Rio de Janeiro, Centre for Health SciencesRio de JaneiroBrazil

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