Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1976 Dec;85(3):623–650.

Oxygen toxicity in the newborn. The effect of chronic continuous 100 percent oxygen exposure on the lungs of newborn mice.

D S Bonikos, K G Bensch, W H Northway Jr
PMCID: PMC2032655  PMID: 998734

Abstract

Continuous exposure of newborn mice of a single, highly inbred strain to 100% oxygen at normal atmospheric pressure for up to 6 weeks resulted in a progressive evolution of pulmonary changes which consisted of dense fibrous tissue deposition, chronic bronchitis and bronchiolitis, and emphysema. Survival of the experimental animals decreased with the duration of exposure, and it was 18% after the sixth week. While the pulmonary changes were evolving, lung growth was markedly inhibited in the experimental animals, whereas lung weight increased significantly. The present study indicates that in contrast to the adult mouse, survival of a substantial percentage of newborn mice for at least 6 weeks is possible, but it is associated with severe changes in pulmonary structure that doubtlessly lead to serious derangement of cardiopulmonary functions.

Full text

PDF
623

Images in this article

Selected References

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

  1. Adamson I. Y., Bowden D. H. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol. 1974 Nov;77(2):185–197. [PMC free article] [PubMed] [Google Scholar]
  2. Adamson I. Y., Bowden D. H. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest. 1974 Jan;30(1):35–42. [PubMed] [Google Scholar]
  3. Adamson I. Y., Bowden D. H., Wyatt J. P. A pathway to pulmonary fibrosis: an ultrastructural study of mouse and rat following radiation to the whole body and hemithorax. Am J Pathol. 1970 Mar;58(3):481–498. [PMC free article] [PubMed] [Google Scholar]
  4. Adamson I. Y., Bowden D. H., Wyatt J. P. Oxygen poisoning in mice. Ultrastructural and surfactant studies during exposure and recovery. Arch Pathol. 1970 Nov;90(5):463–472. [PubMed] [Google Scholar]
  5. Anderson W. R., Strickland M. B. Pulmonary complications of oxygen therapy in the neonate. Postmortem study of bronchopulmonary dysplasia with emphasis on fibroproliferative obliterative bronchitis and bronchiolitis. Arch Pathol. 1971 Jun;91(6):506–514. [PubMed] [Google Scholar]
  6. Anderson W. R., Strickland M. B., Tsai S. H., Haglin J. J. Light microscopic and ultrastructural study of the adverse effects of oxygen therapy on the neonate lung. Am J Pathol. 1973 Nov;73(2):327–348. [PMC free article] [PubMed] [Google Scholar]
  7. BOSS J. H., CRAIG J. M. Reparative phenomena in lungs of neonates with hyaline membranes. Pediatrics. 1962 Jun;29:890–898. [PubMed] [Google Scholar]
  8. Banerjee C. K., Girling D. J., Wigglesworth J. S. Pulmonary fibroplasia in newborn babies treated with oxygen and artificial ventilation. Arch Dis Child. 1972 Aug;47(254):509–518. doi: 10.1136/adc.47.254.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bartlett D., Jr Postnatal growth of the mammalian lung: influence of low and high oxygen tensions. Respir Physiol. 1970 Apr;9(1):58–64. doi: 10.1016/0034-5687(70)90006-x. [DOI] [PubMed] [Google Scholar]
  10. Berman I. R. Intravascular microaggregation and the respiratory distress syndromes. Pediatr Clin North Am. 1975 May;22(2):275–287. doi: 10.1016/s0031-3955(16)33129-7. [DOI] [PubMed] [Google Scholar]
  11. Boat T. F., Kleinerman J. I., Fanaroff A. A., Matthews L. W. Toxic effects of oxygen on cultured human neonatal respiratory epithelium. Pediatr Res. 1973 Jul;7(7):607–615. doi: 10.1203/00006450-197307000-00002. [DOI] [PubMed] [Google Scholar]
  12. Bonikos D. S., Bensch K. G., Ludwin S. K., Northway W. H., Jr Oxygen toxicity in the newborn. The effect of prolonged 100 per cent O2 exposure on the lungs of newborn mice. Lab Invest. 1975 May;32(5):619–635. [PubMed] [Google Scholar]
  13. Bowden D. H., Adamson I. Y. Endothelial regeneration as a marker of the differential vascular responses in oxygen-induced pulmonary edema. Lab Invest. 1974 Mar;30(3):350–357. [PubMed] [Google Scholar]
  14. Chew D. T., Yin A. L. Oxygen therapy and pulmonary fibroplasia: a review and case reports. Med J Malaya. 1971 Dec;26(2):122–128. [PubMed] [Google Scholar]
  15. Crawford L. V., Stout R. H. Obstructive emphysema in pre-school children. Ann Allergy. 1970 Jan;28(1):17–23. [PubMed] [Google Scholar]
  16. DeLemos R., Wolfsdorf J., Nachman R., Block A. J., Leiby G., Wilkinson H. A., Allen T., Haller J. A., Morgan W., Avery M. E. Lung injury from oxygen in lambs: the role of artificial ventilation. Anesthesiology. 1969 Jun;30(6):609–618. doi: 10.1097/00000542-196906000-00007. [DOI] [PubMed] [Google Scholar]
  17. Divertie M. B., Cassan S. M., Brown A. L., Jr Ultrastructural morphometry of the diffusion surface in a case of pulmonary asbestosis. Mayo Clin Proc. 1975 Apr;50(4):193–197. [PubMed] [Google Scholar]
  18. Evans M. J., Cabral L. J., Stephens R. J., Freeman G. Renewal of alveolar epithelium in the rat following exposure to NO2. Am J Pathol. 1973 Feb;70(2):175–198. [PMC free article] [PubMed] [Google Scholar]
  19. Farr G. H., Harley R. A., Hennigar G. R. Desquamative interstitial pneumonia. An electron microscopic study. Am J Pathol. 1970 Sep;60(3):347–370. [PMC free article] [PubMed] [Google Scholar]
  20. Gabbiani G., Majno G. Dupuytren's contracture: fibroblast contraction? An ultrastructural study. Am J Pathol. 1972 Jan;66(1):131–146. [PMC free article] [PubMed] [Google Scholar]
  21. Goldenberg V. E., Warren S., Chute R., Besen M. Radiation pneumonitis in single and parabiotic rats. I. Short term effects of supralethal total body irradiation. Lab Invest. 1968 Mar;18(3):215–226. [PubMed] [Google Scholar]
  22. Gosselin R. E. Physiologic regulators of ciliary motion. Am Rev Respir Dis. 1966 Mar;93(3 Suppl):41–60. doi: 10.1164/arrd.1966.93.3P2.41. [DOI] [PubMed] [Google Scholar]
  23. Gould V. E., Miller J. Sclerosing alveolitis induced by cyclophosphamide. Ultrastructural observations on alveolar injury and repair. Am J Pathol. 1975 Dec;81(3):513–530. [PMC free article] [PubMed] [Google Scholar]
  24. Gould V. E., Tosco R., Wheelis R. F., Gould N. S., Kapanci Y. Oxygen pneumonitis in man. Ultrastructural observations on the development of alveolar lesions. Lab Invest. 1972 May;26(5):499–508. [PubMed] [Google Scholar]
  25. HELLSTROEM B. THE EFFECT OF HIGH OXYGEN CONCENTRATIONS AND HYPOTHERMIA ON THE LUNG OF THE NEWBORN MOUSE. Acta Paediatr Scand. 1965 Sep;54:457–466. doi: 10.1111/j.1651-2227.1965.tb06401.x. [DOI] [PubMed] [Google Scholar]
  26. Hance A. J., Crystal R. G. The connective tissue of lung. Am Rev Respir Dis. 1975 Nov;112(5):657–711. doi: 10.1164/arrd.1975.112.5.657. [DOI] [PubMed] [Google Scholar]
  27. Harrison G. A. Ultrastructural changes in rat lung during long-term exposure to oxygen. Exp Med Surg. 1971;29(1):96–107. [PubMed] [Google Scholar]
  28. Harrison G., Rosan R. C., Sloane A. Bronchiolitis induced by experimental acute and chronic oxygen intoxication in young adult rats. J Pathol. 1970 Oct;102(2):115–122. doi: 10.1002/path.1711020207. [DOI] [PubMed] [Google Scholar]
  29. Heppleston A. G., Styles J. A. Activity of a macrophage factor in collagen formation by silica. Nature. 1967 Apr 29;214(5087):521–522. doi: 10.1038/214521a0. [DOI] [PubMed] [Google Scholar]
  30. Kapanci Y., Assimacopoulos A., Irle C., Zwahlen A., Gabbiani G. "Contractile interstitial cells" in pulmonary alveolar septa: a possible regulator of ventilation-perfusion ratio? Ultrastructural, immunofluorescence, and in vitro studies. J Cell Biol. 1974 Feb;60(2):375–392. doi: 10.1083/jcb.60.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kapanci Y., Weibel E. R., Kaplan H. P., Robinson F. R. Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies. Lab Invest. 1969 Jan;20(1):101–118. [PubMed] [Google Scholar]
  32. Kaplan H. P., Robinson F. R., Kapanci Y., Weibel E. R. Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. I. Clinical and light microscopic studies. Lab Invest. 1969 Jan;20(1):94–100. [PubMed] [Google Scholar]
  33. Kistler G. S., Caldwell P. R., Weibel E. R. Development of fine structural damage to alveolar and capillary lining cells in oxygen-poisoned rat lungs. J Cell Biol. 1967 Mar;32(3):605–628. doi: 10.1083/jcb.32.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Laros C. D. The pathogenesis of lung emphysema. A hypothesis. Respiration. 1972;29(5):442–457. doi: 10.1159/000192914. [DOI] [PubMed] [Google Scholar]
  35. Laurenzi G. A., Yin S., Guarneri J. J. Adverse effect of oxygen on tracheal mucus flow. N Engl J Med. 1968 Aug 15;279(7):333–339. doi: 10.1056/NEJM196808152790701. [DOI] [PubMed] [Google Scholar]
  36. Ludwin S. K., Northway W. H., Jr, Bensch K. G. Oxygen toxicity in the newborn. Necrotizing bronchiolitis in mice exposed to 100 per cent oxygen. Lab Invest. 1974 Nov;31(5):425–435. [PubMed] [Google Scholar]
  37. Moolten S. E. Pulmonary lymphatics in relation to pulmonary clearance and interstitial fluid and their possible implication in the pathogenesis of emphysema. Mt Sinai J Med. 1974 May-Jun;41(3):412–434. [PubMed] [Google Scholar]
  38. Northway W. H., Jr, Petriceks R., Shahinian L. Quantitative aspects of oxygen toxicity in the newborn: inhibition of lung DNA synthesis in the mouse. Pediatrics. 1972 Jul;50(1):67–72. [PubMed] [Google Scholar]
  39. Northway W. H., Jr, Rosan R. C., Porter D. Y. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967 Feb 16;276(7):357–368. doi: 10.1056/NEJM196702162760701. [DOI] [PubMed] [Google Scholar]
  40. Northway W. H., Jr, Rosan R. C., Shahinian L., Jr, Castellino R. A., Gyepes M. T., Durbridge T. Radiologic and histologic investigation of pulmonary oxygen toxicity in newborn guinea pigs. Invest Radiol. 1969 May-Jun;4(3):148–155. doi: 10.1097/00004424-196905000-00002. [DOI] [PubMed] [Google Scholar]
  41. Polgar G., Antagnoli W., Ferrigan L. W., Martin E. A., Gregg W. P. The effect of chronic exposure to 100 percent oxygen in newborn mice. Am J Med Sci. 1966 Nov;252(5):580–587. [PubMed] [Google Scholar]
  42. Resnick J. S., Brown D. M., Vernier R. L. Oxygen toxicity in fetal organ culture. II. The developing lung. Lab Invest. 1974 Dec;31(6):665–677. [PubMed] [Google Scholar]
  43. Rhodes P. G., Hall R. T., Leonidas J. C. Chronic pulmonary disease in neonates with assisted ventilation. Pediatrics. 1975 Jun;55(6):788–796. [PubMed] [Google Scholar]
  44. Richards R. J., Wusteman F. S., Dodgson K. S. The direct effects of dusts on lung fibroblasts grown in vitro. Life Sci I. 1971 Oct 15;10(20):1149–1159. doi: 10.1016/0024-3205(71)90275-x. [DOI] [PubMed] [Google Scholar]
  45. Rosenbaum R. M., Wittner M., Lenger M. Mitochondrial and other ultrastructural changes in great alveolar cells of oxygen-adapted and poisoned rats. Lab Invest. 1969 Jun;20(6):516–528. [PubMed] [Google Scholar]
  46. Rowland R., Newman C. G. Pulmonary complications of oxygen therapy. J Clin Pathol. 1969 Mar;22(2):192–198. doi: 10.1136/jcp.22.2.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ryan G. B., Cliff W. J., Gabbiani G., Irle C., Statkov P. R., Majno G. Myofibroblasts in an avascular fibrous tissue. Lab Invest. 1973 Aug;29(2):197–206. [PubMed] [Google Scholar]
  48. Scadding J. G., Hinson K. F. Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs). Correlation of histology at biopsy with prognosis. Thorax. 1967 Jul;22(4):291–304. doi: 10.1136/thx.22.4.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Schaffner F., Felig P., Trachtenberg E. Structure of rat lung after protracted oxygen breathing. Arch Pathol. 1967 Jan;83(1):99–107. [PubMed] [Google Scholar]
  50. Watanabe S., Watanabe K., Oishi T., Aiba M., Kageyama K. Mast cells in the rat alveolar septa undergoing fibrosis after ionizing irradiation. Ultrastructural and histochemical studies. Lab Invest. 1974 Nov;31(5):555–567. [PubMed] [Google Scholar]
  51. Weibel E. R. Functional morphology of the growing lung. Respiration. 1970;27(Suppl):27–35. doi: 10.1159/000192716. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES