RESTRICTIVE LUNG-DISEASE IN RATS EXPOSED CHRONICALLY TO AN URBAN PROFILE OF OZONE

The potential for irreversible lung impairment resulting from life-lon g ozone (O-3) exposure remains uncertain. To address this question, yo ung adult rats (male, F-344) were exposed to a simulated urban profile of O-3 for 1, 3, 13, 52, or 78 wk, after which pulmonary function tes ts were performed. To assess reversibility of effects, cohorts from th e 13-, 52-, and 78-wk groups were evaluated, respectively, after an ad ditional 6, 27, and 17 wk of clean air. Static and dynamic lung proper ties were based on measurements of lung volume apportionment, respirat ory system compliance (C-rs), DL(CO), multibreath N-2 washout, and max imum expiratory flow-volume relationships. Electrocardiography was als o performed in unanesthetized, restrained rats after 52 and 78 wk, as were determinations of wet and dry lung weights, lung collagen, and as sociated connective tissue crosslinks. Small (< 10%) but significant r eductions in TLC and RV were noted after 13, 52, and 78 wk of O-3 expo sure. At 13 and 52 wk, N-2 washout was enhanced, though at 78 wk it wa s similar to control. None of these changes appeared progressive with continued O-3 exposure. Post exposure to Clean air did not completely reverse the reduction in TLC. Additionally, C-rs, though not affected during O-3 exposure, decreased during the air recovery. No O-3-related changes in collagen were apparent, however. Thus, near life-long expo sure of F-344 rats to a worse-case, urban profile of O-3 appears to ha ve led to a functionally restrictive, i.e. ''stiffened,'' lung without overt fibrosis. Furthermore, certain aspects of the O-3-induced effec t were not fully reversible.