Chest
Volume 123, Issue 2, February 2003, Pages 530-538
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Laboratory and Animal Investigations
Neonatal Exposure to 65% Oxygen Durably Impairs Lung Architecture and Breathing Pattern in Adult Mice*

https://doi.org/10.1378/chest.123.2.530Get rights and content

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% O2 (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/mm2 vs 578 ± 77/mm2, 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 H2O) than in normoxic mice (0.064 ± 0.006 mL/cm H2O, 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 V˙e, and V˙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 O2 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.

Section snippets

Mice

Six Swiss female mice (IFFA-CREDO; L’Arbresle, France) were housed at 24°C with a 12 h/12h light/dark cycle and food and water ad libitum. These female mice were mated with Swiss male mice. Three pregnant females were randomly assigned to the hyperoxic group, and three pregnant females were assigned to the normoxic group. The hyperoxic female mice gave birth to 24 pups (10 males and 14 females), and the normoxia female mice gave birth to 19 pups (10 males and 9 females). Experimental protocols

Weight

The hyperoxic mice showed normal aspect and behavior. Neither weight, which increased normally with PNA (Fig 1), nor rectal temperature, which remained steady throughout the study period, was significantly different in hyperoxic and normoxic mice (37.5 ± 0.6°C vs 37.4 ± 0.3°C).

Breathing Pattern

Baseline Vt and Ttot were slightly but significantly larger in hyperoxic mice than in normoxic mice at all PNAs (Fig 2). The longer Ttot values in hyperoxic mice were caused by significantly longer Ti and expiratory

Discussion

This study shows that 28-day postnatal exposure to 65% O2 in mice causes long-term changes in pulmonary structure and breathing pattern. Seven months after 65% O2 hyperoxic exposure, the mice had reduced alveolarization, enlarged alveolar spaces, fibrotic lesions, increased Crs, lower baseline breathing frequency, and larger Vt than normoxic control mice. In contrast, hyperoxic exposure did not cause major impairments of respiratory homeostasis, as suggested by blood gas values, baseline

Conclusion

Hyperoxic exposure during lung septation in mice may cause irreversible lung injury and breathing pattern abnormalities in adulthood at O2 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.

ACKNOWLEDGMENT

We thank Dr. Caroline Rambaud (Service d’Anatomo-Pathologie, Hôpital Antoine-Béclère, Université Paris XI) for her careful reading of a previous version of the article.

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    This study was supported by the Institut National de la Santé et de la Recherche Médicale (grant awarded to Dr. Dauger), and the Université Paris VII (Legs Poix).

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