DETERMINANTS OF INHALED OZONE ABSORPTION IN ISOLATED RAT LUNGS

Using an isolated rat lung model, we investigated the characteristics of pulmonary O-3 absorption, including the contributory role of chemical reaction vs physical solubility. Due to the physicochemical similarities between O-3 and NO2, we utilized investigational strategies analogous to those previously employed to characterize NO2 absorption kinetics. The effects of vascular perfusion, temperature, inspired concentration ([O-3](i)), surface area, and minute ventilation (tidal volume (V-t) times ventilation frequency (f)) on air space O-3 clearance during quasi-steady-state exposures were investigated using fractional uptakes (%U) and reactive uptake coefficients (k') as endpoints. We found the following: (1) At 1 ppm [O-3](i) (37 degrees C), %U (95 +/- 5%) was perfusion independent (60 min). (2) %U displayed temperature dependence (r = 0.99). Activation energies (E(a)) and Q(10) were computed from Arrhenius plots (ln k' vs 1/T; r = -0.99). For 1 ppm (11-37 degrees C), E(a) = 4140 kcal/g.mol and Q(10) = 1.23. (3) Absorption demonstrated [O-3](i) dependence. At 25 degrees C, less than or equal to 1 ppm displayed %U= 86 +/- 4% with k' = 234 ml/min. Exposures >1 ppm resulted in decreasing %U and k' (5 ppm %U = 60 +/- 3% and k' = 121 ml/min). (4) To evaluate epithelial damage,lactate dehydrogenase (LDH) activity was quantified in cell-free bronchoalveolar lavage fluid. For exposures less than or equal to 1 ppm LDH equaled control, while for exposures >1 ppm LDH steadily increased to a fourfold maximum at 5 ppm. (5) O-3 uptake was independent of functional residual capacity-induced changes in air space surface area. (6) Absorption was proportional to V-t (r = 0.99) and displayed notable ventilation frequency-dependent decline above 70 breaths per minute. Based on the perfusion independence, temperature dependence, and the E(a) and Q(10), we conclude that O-3 absorption in isolated lungs involves a reactive component. While k' remained stable from 0 to 1 ppm O-3, at concentrations above 1 ppm-other contributory factors such as O-3/substrate reaction kinetics, epithelial damage, and solute O-3 backpressure may affect the overall net absorption rate. In addition, the data suggest that O-3 uptake may be principally localized to the conducting airways. (C) 1994 Academic Press, Inc.