title: Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway.
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.
authors.affiliation: Division of Neonatology, Rainbow Babies & Children's Hospital and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Neonatology, Rainbow Babies & Children's Hospital and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Anjum
authors.initials: A
authors.lastname: Jafri
authors.affiliation: Division of Neonatology, Rainbow Babies & Children's Hospital and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio; rxm6@case.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Division of Neonatology, Rainbow Babies & Children's Hospital and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Jerry
authors.initials: J
authors.lastname: Nnanabu
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio; and.
authors.forename: Carol
authors.initials: C
authors.lastname: Farver
authors.affiliation: Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
authors.affiliation: Division of Neonatology, Rainbow Babies & Children's Hospital and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Peter M
authors.initials: PM
authors.lastname: MacFarlane
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D010100:Oxygen / Q000633:toxicity*; D012137:Respiratory System / Q000254:growth & development* / Q000503:physiopathology
chemical_list: D016210:Methacholine Chloride; D003094:Collagen; D010100:Oxygen
keywords: airway; hyperoxia; hyperreactivity; neonate; oxygen