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. 1981 Jun;103(3):376–383.

Oleic-acid-induced lung injury in the rat. Failure of indomethacin treatment or complement depletion to ablate lung injury.

B F Dickey, R S Thrall, J R McCormick, P A Ward
PMCID: PMC1903842  PMID: 7234970

Abstract

The purpose of this study was to establish a rat animal model of acute respiratory distress syndrome using the intravenous injection of oleic acid. Further, we attempted to inhibit the development of lung injury by pretreatment of the rats with indomethacin or cobra venom factor. Histologic evidence of lung injury was apparent within hours after the administration of a single intravenous injection of oleic acid. By 24 hours, interstitial and intraalveolar edema and hemorrhage were noted with vascular congestion and an extensive interstitial infiltrate. The lungs appeared virtually normal by 12 days, with no evidence of chronic lung injury. Multiple injections of oleic acid also did not progress into chronic pulmonary inflammation. Treatment of the rats with indomethacin or cobra venom factor had no effect on ablating acute lung injury. An animal model of adult respiratory distress syndrome is presented which does not progress to chronic lung injury.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashbaugh D. G., Bigelow D. B., Petty T. L., Levine B. E. Acute respiratory distress in adults. Lancet. 1967 Aug 12;2(7511):319–323. doi: 10.1016/s0140-6736(67)90168-7. [DOI] [PubMed] [Google Scholar]
  2. Ashbaugh D. G., Petty T. L. The use of corticosteroids in the treatment of respiratory failure associated with massive fat embolism. Surg Gynecol Obstet. 1966 Sep;123(3):493–500. [PubMed] [Google Scholar]
  3. Ashbaugh D. G., Uzawa T. Respiratory and hemodynamic changes after injection of free fatty acids. J Surg Res. 1968 Sep;8(9):417–423. doi: 10.1016/0022-4804(68)90057-7. [DOI] [PubMed] [Google Scholar]
  4. BERGENTZ S. E. Studies on the genesis of posttraumatic fat embolism. Acta Chir Scand Suppl. 1961;Suppl 282:1–72. [PubMed] [Google Scholar]
  5. Baker P. L., Kuenzig M. C., Peltier L. F. Experimental fat embolism in dogs. J Trauma. 1969 Jul;9(7):577–586. doi: 10.1097/00005373-196907000-00002. [DOI] [PubMed] [Google Scholar]
  6. Bradford D. S., Foster R. R., Nossel H. L. Coagulation alterations, hypoxemia, and fat embolism in fracture patients. J Trauma. 1970 Apr;10(4):307–321. doi: 10.1097/00005373-197004000-00004. [DOI] [PubMed] [Google Scholar]
  7. Bradley B. E., Jr, Vracko R., Sullivan K. N., Fry L. H., Akeson W. H. Corticosteroids as treatment for chemical pneumonitis induced by intravenous oleic acid. Clin Orthop Relat Res. 1972 Jul-Aug;86:230–236. doi: 10.1097/00003086-197207000-00035. [DOI] [PubMed] [Google Scholar]
  8. CONNOR W. E., HOAK J. C., WARNER E. D. Massive thrombosis produced by fatty acid infusion. J Clin Invest. 1963 Jun;42:860–866. doi: 10.1172/JCI104778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cahill J. M., Daly B. F., Byrne J. J. Ventilatory and circulatory response to oleic acid embolus. J Trauma. 1974 Jan;14(1):73–76. doi: 10.1097/00005373-197401000-00010. [DOI] [PubMed] [Google Scholar]
  10. Delahunty T. J., Spitzer H. L., Jimenez J. M., Johnston J. M. Phosphatidate phosphohydrolase activity in porcine pulmonary surfactant. Am Rev Respir Dis. 1979 Jan;119(1):75–80. doi: 10.1164/arrd.1979.119.1.75. [DOI] [PubMed] [Google Scholar]
  11. Derks C. M., Jacobovitz-Derks D. Embolic pneumopathy induced by oleic acid. A systematic morphologic study. Am J Pathol. 1977 Apr;87(1):143–158. [PMC free article] [PubMed] [Google Scholar]
  12. Dubois M., Lotze M. T., Diamond W. J., Kim Y. D., Flye M. W., Macnamara T. E. Pulmonary shunting during leukoagglutinin-induced noncardiac pulmonary edema. JAMA. 1980 Nov 14;244(19):2186–2189. [PubMed] [Google Scholar]
  13. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  14. Fonte D. A., Hausberger F. X. Pulmonary free fatty acids in experimental fat embolism. J Trauma. 1971 Aug;11(8):668–672. doi: 10.1097/00005373-197108000-00004. [DOI] [PubMed] [Google Scholar]
  15. From A. H., Gewurz H., Gruninger R. P., Pickering R. J., Spink W. W. Complement in endotoxin shock: effect of complement depletion on the early hypotensive phase. Infect Immun. 1970 Jul;2(1):38–41. doi: 10.1128/iai.2.1.38-41.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fuchsig P., Brücke P., Blümel G., Gottlob R. A new clinical and experimental concept on fat embolism. N Engl J Med. 1967 May 25;276(21):1192–1193. doi: 10.1056/NEJM196705252762107. [DOI] [PubMed] [Google Scholar]
  17. Gemer M., Dunegan L. J., Lehr J. L., Bruner J. D., Stetz C. W., Don H. F., Hayes J. A., Drinker P. A. Pulmonary insufficiency induced by oleic acid in the sheep: a model for investigation of extracorporeal oxygenation. J Thorac Cardiovasc Surg. 1975 May;69(5):793–799. [PubMed] [Google Scholar]
  18. HALASZ N. A., MARASCO J. P. An experimental study of fat embolism. Surgery. 1957 Jun;41(6):921–929. [PubMed] [Google Scholar]
  19. HAMILTON R. W., Jr, HUSTEAD R. F., PELTIER L. F. FAT EMBOLISM: THE EFFECT OF PARTICULATE EMBOLISM ON LUNG SURFACTANT. Surgery. 1964 Jul;56:53–56. [PubMed] [Google Scholar]
  20. Hahn-Pedersen J., Sorensen H., Kehlet H. Complement activation during surgical procedures. Surg Gynecol Obstet. 1978 Jan;146(1):66–68. [PubMed] [Google Scholar]
  21. Hammerschmidt D. E., Weaver L. J., Hudson L. D., Craddock P. R., Jacob H. S. Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome. Pathophysiological relevance and possible prognostic value. Lancet. 1980 May 3;1(8175):947–949. doi: 10.1016/s0140-6736(80)91403-8. [DOI] [PubMed] [Google Scholar]
  22. Hammerschmidt D. E., White J. G., Craddock P. R., Jacob H. S. Corticosteroids inhibit complement-induced granulocyte aggregation. A possible mechanism for their efficacy in shock states. J Clin Invest. 1979 Apr;63(4):798–803. doi: 10.1172/JCI109365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Herndon J. H., Riseborough E. J., Fischer J. E. Fat embolism: a review of current concepts. J Trauma. 1971 Aug;11(8):673–680. [PubMed] [Google Scholar]
  24. Hoak J. C., Connor W. E., Warner E. D. Thrombogenic effects of albumin-bound fatty acids. Arch Pathol. 1966 Feb;81(2):136–139. [PubMed] [Google Scholar]
  25. Jacob H. S., Craddock P. R., Hammerschmidt D. E., Moldow C. F. Complement-induced granulocyte aggregation: an unsuspected mechanism of disease. N Engl J Med. 1980 Apr 3;302(14):789–794. doi: 10.1056/NEJM198004033021407. [DOI] [PubMed] [Google Scholar]
  26. Johnson K. J., Ward P. A. Acute immunologic pulmonary alveolitis. J Clin Invest. 1974 Aug;54(2):349–357. doi: 10.1172/JCI107770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. King E. G., Weily H. S., Genton E., Ashbaugh D. G. Consumption coagulopathy in the canine oleic acid model of fat embolism. Surgery. 1971 Apr;69(4):533–541. [PubMed] [Google Scholar]
  28. Lee W. H., Jr, Cooper N., Murner E. S., Matsuura Y., Najib A. The effects of prolonged cardiopulmonary bypass (two to four hours) upon lung function and respiratory work. Am Surg. 1968 Aug;34(8):624–628. [PubMed] [Google Scholar]
  29. Liljedahl S. O., Westermark L. Aetiology and treatment of fat embolism. Report of five cases. Acta Anaesthesiol Scand. 1967;11(3):177–194. doi: 10.1111/j.1399-6576.1967.tb00383.x. [DOI] [PubMed] [Google Scholar]
  30. Meagher D. M., Piermattei D. L., Swan H. Platelet aggregation during progressive hemorrhagic shock in pigs. Possible effects on the postperfusion syndrome. J Thorac Cardiovasc Surg. 1971 Nov;62(5):822–824. [PubMed] [Google Scholar]
  31. O'Flaherty J. T., Showell H. J., Ward P. A., Becker E. L. A possible role of arachidonic acid in human neutrophil aggregation and degranulation. Am J Pathol. 1979 Sep;96(3):799–810. [PMC free article] [PubMed] [Google Scholar]
  32. PELTIER L. F. Fat embolism. III. The toxic properties of neutral fat and free fatty acids. Surgery. 1956 Oct;40(4):665–670. [PubMed] [Google Scholar]
  33. Peltier L. F. Fat embolism: a pulmonary disease. Surgery. 1967 Oct;62(4):756–758. [PubMed] [Google Scholar]
  34. Pomerantz M., Eiseman B. Experimental shock lung model. J Trauma. 1968 Sep;8(5):782–787. doi: 10.1097/00005373-196809000-00019. [DOI] [PubMed] [Google Scholar]
  35. Ruddy S., Gigli I., Austen K. F. The complement system of man (second of four parts). N Engl J Med. 1972 Sep 14;287(11):545–549. doi: 10.1056/NEJM197209142871106. [DOI] [PubMed] [Google Scholar]
  36. Smith G., Winter P. M., Wheelis R. F. Increased normobaric oxygen tolerance of rabbits following oleic acid-induced lung damage. J Appl Physiol. 1973 Sep;35(3):395–400. doi: 10.1152/jappl.1973.35.3.395. [DOI] [PubMed] [Google Scholar]
  37. Webb W. R. Pulmonary complications of non-thoracic trauma: summary of the national research council conference. J Trauma. 1969 Aug;9(8):700–711. [PubMed] [Google Scholar]
  38. Weiss H. J. The pharmacology of platelet inhibition. Prog Hemost Thromb. 1972;1:199–231. [PubMed] [Google Scholar]
  39. Zucker M. B., Peterson J. Effect of acetylsalicylic acid, other nonsteroidal anti-inflammatory agents, and dipyridamole on human blood platelets. J Lab Clin Med. 1970 Jul;76(1):66–75. [PubMed] [Google Scholar]

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