Bj. Finlaysonpitts et al., ARE CHANGES IN BREATHING PATTERN ON EXPOSURE TO OZONE RELATED TO CHANGES IN PULMONARY SURFACTANT, Inhalation toxicology, 6(3), 1994, pp. 267-287
Rats respond to the inhalation of ozone with changes in breathing patt
ern during the exposure and the development of a pulmonary inflammator
y response 24-48 h postexposure. We report experiments designed to inv
estigate the relationships between changes in breathing pattern and th
e composition and surface tension-reducing properties of pulmonary sur
factant immediately after the exposure. A total of 64 male Fischer 344
rats were exposed to 0.8 ppm O3 for 4 h in 4 replicate exposures with
matched purified air control exposures and 8 rats per exposure group.
Those exposed to O3 developed the rapid-shallow breathing pattern cha
racteristic of oxidant pulmonary irritation during exposure. The rats
were sacrificed immediately following the exposure, and pulmonary surf
actant was isolated from samples of bronchoalveolar lavage fluid poole
d from groups of eight rats. After esterification, the fatty acid meth
yl ester composition was measured using GC-MS. In the ozone-exposed an
imals, the decreases in unsaturated species (linoleic, oleic, palmitol
eic, and an unidentified fatty acid) relative to the major saturated c
omponent, palmitic acid, were highly statistically significant, while
stearic acid showed no significant change. Total protein in the lavage
fluids of the exposed animals was not elevated, indicating that sacri
fice and analysis were performed early in the O3 injury-inflammation r
esponse sequence, and suggesting that the fatty acid changes in the pu
lmonary surfactant may be due in part to a direct reaction with inhale
d O3. The group mean change in breath frequency (as percent of matched
purified air control values) was significantly correlated with the pe
rcent change in linoleic acid fraction among replicate exposures, sugg
estive of a possible relationship between ozone-induced changes in pul
monary surfactant and changes in breathing patterns. There was no sign
ificant change in the surface pressure-area isotherms of monolayers of
pulmonary surfactant upon ozone exposure. However, comparison to isot
herms from an in vitro exposure of a synthetic mixture of saturated an
d unsaturated phospholipids suggests that changes due to the observed
change in the fatty acid composition in the in vivo experiments may be
too small to be observed. Furthermore, the pulmonary surfactant isola
tion procedure was specifically designed to recover the undamaged surf
actant and may discriminate against products of reaction with ozone; h
ence the isotherms may not necessarily reflect the actual changes duri
ng the exposure. Further experiments to elucidate the interaction of i
nhaled O3 with pulmonary surfactant and its relationship to changes in
breathing pattern are discussed.