Cumulative effects of neonatal hyperoxia on murine alveolar structure and function

Angela M. Cox, Yong Gao, Anne Karina T Perl, Robert Tepper, Shawn K. Ahlfeld

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Bronchopulmonary dysplasia (BPD) results from alveolar simplification and abnormal development of alveolar and capillary structure. Survivors of BPD display persistent deficits in airflow and membrane and vascular components of alveolar gas diffusion. Despite being the defining feature of BPD, various neonatal hyperoxia models of BPD have not routinely assessed pulmonary gas diffusion. Methods: To simulate the most commonly-utilized neonatal hyperoxia models, we exposed neonatal mice to room air or ≥90% hyperoxia during key stages of distal lung development: through the first 4 (saccular), 7 (early alveolar), or 14 (bulk alveolar) postnatal days, followed by a period of recovery in room air until 8 weeks of age when alveolar septation is essentially complete. We systematically assessed and correlated the effects of neonatal hyperoxia on the degree of alveolar-capillary structural and functional impairment. We hypothesized that the degree of alveolar-capillary simplification would correlate strongly with worsening diffusion impairment. Results: Neonatal hyperoxia exposure, of any duration, resulted in alveolar simplification and impaired pulmonary gas diffusion. Mean Linear Intercept increased in proportion to the length of hyperoxia exposure while alveolar and total lung volume increased markedly only with prolonged exposure. Surprisingly, despite having a similar effect on alveolar surface area, only prolonged hyperoxia for 14 days resulted in reduced pulmonary microvascular volume. Estimates of alveolar and capillary structure, in general, correlated poorly with assessment of gas diffusion. Conclusion: Our results help define the physiological and structural consequences of commonly-employed neonatal hyperoxia models of BPD and inform their clinical utility.

Original languageEnglish (US)
JournalPediatric Pulmonology
DOIs
StateAccepted/In press - 2017

Fingerprint

Hyperoxia
Bronchopulmonary Dysplasia
Lung
Gases
Air
Recovery Room
Blood Vessels
Membranes

Keywords

  • Bronchopulmonary dysplasia
  • Hyperoxia
  • Lung function
  • Neonatal
  • Pulmonary diffusion capacity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Cumulative effects of neonatal hyperoxia on murine alveolar structure and function. / Cox, Angela M.; Gao, Yong; Perl, Anne Karina T; Tepper, Robert; Ahlfeld, Shawn K.

In: Pediatric Pulmonology, 2017.

Research output: Contribution to journalArticle

Cox, Angela M. ; Gao, Yong ; Perl, Anne Karina T ; Tepper, Robert ; Ahlfeld, Shawn K. / Cumulative effects of neonatal hyperoxia on murine alveolar structure and function. In: Pediatric Pulmonology. 2017.
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