Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats.
Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease in premature infants. Airway inflammation appears to play a major pathogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%) on airway reactivity and inflammatory response in neonatal and adult rats. We studied in isolated tracheal rings the 1) isometric contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly increased in the hyperoxic pups, in which a 13% increase in tracheal smooth muscle surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, morphometric, or cellular data in adult rats. In conclusion, exposure of newborn rats to moderate hyperoxia induces airway hyperresponsiveness and histologic changes similar to those reported in bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltrating the airways. Lung immaturity definitely plays a role because similar alterations are not observed in adult rats.
Denis
D
D
Pediatric Intensive Care and Pulmonology Units, Hôpital Pellegrin-Enfants, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France.
Fayon
M J
MJ
Berger
P
P
Molimard
M
M
De Lara
M T
MT
Roux
E
E
Marthan
R
R
D000818:Animals; D000831:Animals, Newborn; D016535:Bronchial Hyperreactivity; D018496:Hyperoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D007537:Isometric Contraction; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000503:physiopathology*