Recovery of airway structure and function after hyperoxic exposure in immature rats

Marc B. Hershenson*, Mark K. Abe, Michael D. Kelleher, Edward T. Naureckas, Allan Garland, Anne Zimmermann, Valeria J. Rubinstein, Julian Solway

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


We have previously demonstrated that hyperoxic exposure (>95% O2 for 8 d) induces airway cholinergic hyperresponsiveness and remodeling in 21-d-old rats. To examine the potential relationship between airway hyperresponsiveness and remodeling in these animals, we exposed rats to air or hyperoxia for 8 d, returned them to air-breathing, and measured airway responsiveness to inhaled acetylcholine (ACh) and layer thicknesses immediately after or 16 or 48 d after cessation of air or O2 exposure. The ACh concentration required to increase resistance by 100% (EC200ACh) was calculated by linear interpolation. Small airway (circumference < 1,000 μm) and medium-sized, conducting airway (1,000 to 3,000 μm) epithelial and smooth muscle layer mean thicknesses and fractional areas (layer area/luminal cross-sectional area) were determined from lung sections by contour tracing using a digitizing pad and computer. As we reported previously, after 8 d of O2 exposure, group mean log, EC200ACh was significantly reduced relative to that in control animals (p < 0.001). Similarly, hyperoxic exposure was associated with significant increases in all parameters of airway layer thickness assessed (p < 0.05). However, by 16 d after cessation of O2 exposure, there were no longer statistically significant differences in log EC200ACh, airway layer thickness, or fractional area between control and O2-exposed animals. Further studies, in a second cohort of animals killed 0, 3, 6, 8, or 13 d after cessation of O2 exposure, demonstrated progressive reductions in small airway epithelial and smooth muscle layer thicknesses, confirming that hyperoxia-induced airway remodeling resolves by approximately 2 wk after termination of O2 exposure. We conclude that hyperoxia-induced airway hyperresponsiveness and remodeling are reversible after O2 exposure. Improvements in airway structure and function occurred in parallel, supporting the notion that airway remodeling determines airway responsiveness in these animals.

Original languageEnglish (US)
Pages (from-to)1663-1669
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number6
StatePublished - Jun 1994

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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