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


METHODS
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.


CONCLUSIONS
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.
Dauger
Stéphane
S
The Institut National de la Santé et de la Recherche Médicale, Paris, France.
Ferkdadji
Latifa
L
Saumon
Georges
G
Vardon
Guy
G
Peuchmaur
Michel
M
Gaultier
Claude
C
Gallego
Jorge
J
D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000097:blood; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010100:Oxygen / Q000097:blood / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology
D002245:Carbon Dioxide; D010100:Oxygen