Hyperoxic lung injury: Biochemical cellular, and morphologic characterization in the mouse

Lewis J. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Controversy exists over the mechanism by which oxygen produces lung damage. This study was designed to characterize the biochemical, cellular, and morphologic responses of mice exposed to 100% oxygen and thereby provide the basis for investigating the mechanisms producing the lung damage as well as for evaluating treatment strategies. After 1 day of exposure, plasma lactate dehydrogenase (LDH) activity and LDH isoenzyme 1, 2, and 3 concentration increased, whereas the level of isoenzyme 1 recovered from the lung, heart, and kidney decreased. On day 2, the level of these plasma isoenzymes increased further, whereas isoenzyme 1 concentration remained decreased only in the lung. In addition, the number of cells obtained by bronchoalveolar lavage (BAL) doubled, and electron microscopy revealed type 1 cell and endothelial cell damage. On day 3, the amount of BAL protein doubled, BAL angiotensin-converting enzyme (ACE) activity increased sevenfold, plasma ACE activity decreased 39%, and electron microscopy revealed extensive cell damage. On day 4, the injury was much worse and was associated with a 10-fold increase in the number of BAL cells, nearly all of which were polymorphonuclear leukocytes (PMNs). On day 5, >65% of the mice were dead. The data suggest that in mice (1) an increase in plasma LDH activity and a shift in its isoenzyme pattern are sensitive markers of hyperoxic lung damage, (2) the initial injury produced by oxygen is independent of PMNs, and (3) the damage to alveolar epithelial cells and endothelial cells is severe and occurs at the same time. Studies using this well-characterized model can now be designed to further define the mechanisms that initiate hyperoxic lung damage and that contribute to its progression.

Original languageEnglish (US)
Pages (from-to)269-278
Number of pages10
JournalThe Journal of laboratory and clinical medicine
Issue number3
StatePublished - Sep 1985

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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