Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway

Hua Wang, Anjum Jafri, Richard J. Martin, Jerry Nnanabu, Carol Farver, Y.s. Prakash, Peter M. MacFarlane

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Wheezing is a major long-term respiratory morbidity in preterm infants with and without bronchopulmonary dysplasia. We hypothesized that mild vs. severe hyperoxic exposure in neonatal mice differentially affects airway smooth muscle hypertrophy and resultant airway reactivity. Newborn mice were exposed to 7 days of mild (40% oxygen) or severe (70% oxygen) hyperoxia vs. room air controls. Respiratory system resistance (Rrs), compliance (Crs), and airway reactivity were measured 14 days after oxygen exposure ended under ketamine/xylazine anesthesia. Baseline Rrs increased and Crs decreased in both treatment groups. Methacholine challenge dose dependently increased Rrs and decreased Crs in 40% oxygen-exposed mice, whereas Rrs and Crs responses were similar between 70% oxygen-exposed and normoxic controls. Airway smooth muscle thickness was increased in 40%- but not 70%-exposed mice, whereas collagen increased and both alveolar number and radial alveolar counts decreased after 40% and 70% oxygen. These data indicate that severity of hyperoxia may differentially affect structural and functional changes in the developing mouse airway that contribute to longer-term hyperreactivity. These findings may be important to our understanding of the complex role of neonatal supplemental oxygen therapy in postnatal development of airway responsiveness.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume307
Issue number4
DOIs
StatePublished - Aug 15 2014

Fingerprint

Hyperoxia
Oxygen
Respiratory System
Smooth Muscle
Xylazine
Bronchopulmonary Dysplasia
Methacholine Chloride
Respiratory Sounds
Ketamine
Premature Infants
Hypertrophy
Compliance
Collagen
Anesthesia
Air
Morbidity
Therapeutics

Keywords

  • Airway
  • Hyperoxia
  • Hyperreactivity
  • Neonate
  • Oxygen

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway. / Wang, Hua; Jafri, Anjum; Martin, Richard J.; Nnanabu, Jerry; Farver, Carol; Prakash, Y.s.; MacFarlane, Peter M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 307, No. 4, 15.08.2014.

Research output: Contribution to journalArticle

Wang, Hua ; Jafri, Anjum ; Martin, Richard J. ; Nnanabu, Jerry ; Farver, Carol ; Prakash, Y.s. ; MacFarlane, Peter M. / Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2014 ; Vol. 307, No. 4.
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