RECOVERY OF AIRWAY STRUCTURE AND FUNCTION AFTER HYPEROXIC EXPOSURE INIMMATURE RATS

We have previously demonstrated that hyperoxic exposure (> 95% O-2 for 8 d) induces airway cholinergic hyperresponsiveness and remodeling in 21-d-old rats. To examine the potential relationship between airway h yperresponsiveness and remodeling in these animals, we exposed rats to air or hyperoxia for 8 d, returned them to air-breathing, and measure d airway responsiveness to inhaled acetylcholine (ACh) and layer thick nesses immediately after or 16 or 48 d after cessation of air or O-2 e xposure. The ACh concentration required to increase resistance by 100% (EC(200)ACh) was calculated by linear interpolation. Small airway (ci rcumference < 1,000 mu m) and medium-sized, conducting airway (1,000 t o 3,000 mu m) epithelial and smooth muscle layer mean thicknesses and fractional areas (layer area/luminal cross-sectional area) were determ ined from lung sections by contour tracing using a digitizing pad and computer. As we reported previously, after 8 d of O-2 exposure, group mean log EC(200)ACh was significantly reduced relative to that in cont rol 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 O-2 exposure , there were no longer statistically significant differences in log EC (200)ACh, airway layer thickness, or fractional area between control a nd O-2-exposed animals. Further studies, in a second cohort of animals killed 0, 3, 6, 8, or 13 d after cessation of O-2 exposure, demonstra ted progressive reductions in small airway epithelial and smooth muscl e layer thicknesses, confirming that hyperoxia-induced airway remodeli ng resolves by approximately 2 wk after termination of O-2 exposure. W e conclude that hyperoxia-induced airway hyperresponsiveness and remod eling are reversible after O-2 exposure. Improvements in airway struct ure and function occurred in parallel, supporting the notion that airw ay remodeling determines airway responsiveness in these animals.