Am. J. Respir. Crit. Care Med., Vol 149, No. 6, 06 1994, 1663-1669.
Recovery of airway structure and function after hyperoxic exposure in immature rats
MB Hershenson, MK Abe, MD Kelleher, ET Naureckas, A Garland, A Zimmermann, VJ Rubinstein and J Solway
Department of Pediatrics, University of Chicago, Illinois.
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)