title: Recovery of airway structure and function after hyperoxic exposure in immature rats.
abstract: 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 microns) and medium-sized, conducting airway (1,000 to 3,000 microns) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, University of Chicago, Illinois.
authors.forename: M B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: M K
authors.initials: MK
authors.lastname: Abe
authors.forename: M D
authors.initials: MD
authors.lastname: Kelleher
authors.forename: E T
authors.initials: ET
authors.lastname: Naureckas
authors.forename: A
authors.initials: A
authors.lastname: Garland
authors.forename: A
authors.initials: A
authors.lastname: Zimmermann
authors.forename: V J
authors.initials: VJ
authors.lastname: Rubinstein
authors.forename: J
authors.initials: J
authors.lastname: Solway
mesh_terms: D000109:Acetylcholine; D000280:Administration, Inhalation; D000336:Aerosols; D000367:Age Factors; D000403:Airway Resistance; D000704:Analysis of Variance; D000818:Animals; D001706:Biopsy; D001835:Body Weight / Q000187:drug effects; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D009130:Muscle, Smooth / Q000473:pathology*; D010100:Oxygen / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000336:Aerosols; D000109:Acetylcholine; D010100:Oxygen