Neonatal exposure to 65% oxygen durably impairs lung architecture and breathing pattern in adult mice

Chest. 2003 Feb;123(2):530-8. doi: 10.1378/chest.123.2.530.


Study objective: To test the hypothesis that exposure to hyperoxia during the postnatal period of rapid alveolar multiplication by septation would cause permanent impairments, even with moderate levels of hyperoxia.

Design: We exposed mouse pups to 65% O(2) (hyperoxic mice) or normoxia (normoxic mice) during their first postnatal month, and we analyzed lung histology, pulmonary mechanics, blood gas, and breathing pattern during normoxia or in response to chemical stimuli in adulthood, when they reached 7 to 8 months of postnatal age.

Results: Hyperoxic mice had fewer and larger alveoli than normoxic mice (number of alveoli per unit surface area of parenchyma, 266 +/- 62/mm(2) vs 578 +/- 77/mm(2), p < 0.0001) [mean +/- SD], the cause being impaired alveolarization (radial alveolar count, 5.8 +/- 0.2 in hyperoxic mice vs 10.5 +/- 0.5 in normoxic mice, p < 0.0001). Respiratory system compliance was higher in hyperoxic mice (0.098 +/- 0.006 mL/cm H(2)O) than in normoxic mice (0.064 +/- 0.006 mL/cm H(2)O, p < 0.016). Baseline tidal volume (VT) and breath duration (TTOT]) measured noninvasively by whole-body plethysmography were larger in hyperoxic mice than in normoxic mice (VT, + 15%, p < 0.01; TTOT, + 12%, p < 0.01). Despite these impairments, blood gas, baseline minute ventilation E, and E responses to hypoxia and hypercapnia were normal in hyperoxic mice, compared with normoxic mice.

Conclusion: Hyperoxic exposure during lung septation in mice may cause irreversible lung injury and breathing pattern abnormalities in adulthood at O(2) concentrations lower than previously thought. However, ventilatory function and body growth were preserved, and ventilatory function showed no major abnormalities, at least at rest, despite early oxygen-induced injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Carbon Dioxide / blood
  • Cell Division / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Hyperoxia / pathology
  • Hyperoxia / physiopathology*
  • Lung Compliance / drug effects
  • Lung Compliance / physiology
  • Mice
  • Oxygen / blood
  • Oxygen / toxicity*
  • Plethysmography, Whole Body
  • Pregnancy
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / pathology
  • Pulmonary Gas Exchange / drug effects
  • Pulmonary Gas Exchange / physiology
  • Respiratory Mechanics / drug effects
  • Respiratory Mechanics / physiology


  • Carbon Dioxide
  • Oxygen