Determinants of inhaled ozone absorption in isolated rat lungs.
Using an isolated rat lung model, we investigated the characteristics of pulmonary O3 absorption, including the contributory role of chemical reaction vs physical solubility. Due to the physicochemical similarities between O3 and NO2, we utilized investigational strategies analogous to those previously employed to characterize NO2 absorption kinetics. The effects of vascular perfusion, temperature, inspired concentration ([O3]i), surface area, and minute ventilation (tidal volume (Vt) times ventilation frequency (f)) on air space O3 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 [O3]i (37 degrees C), %U (95 +/- 5%) was perfusion independent (60 min). (2) %U displayed temperature dependence (r = 0.99). Activation energies (Ea) and Q10 were computed from Arrhenius plots (ln k' vs 1/T; r = -0.99). For 1 ppm (11-37 degrees C), Ea = 4140 kcal/g.mol and Q10 = 1.23. (3) Absorption demonstrated [O3]i dependence. At 25 degrees C, < or = 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 < or = 1 ppm LDH equaled control, while for exposures > 1 ppm LDH steadily increased to a four-fold maximum at 5 ppm. (5) O3 uptake was independent of functional residual capacity-induced changes in air space surface area. (6) Absorption was proportional to Vt (r = 0.99) and displayed notable ventilation frequency-dependent decline above 70 breaths per minute. Based on the perfusion independence, temperature dependence, and the Ea and Q10, we conclude that O3 absorption in isolated lungs involves a reactive component. While k' remained stable from 0 to 1 ppm O3, at concentrations above 1 ppm other contributory factors such as O3/substrate reaction kinetics, epithelial damage, and solute O3 backpressure may affect the overall net absorption rate. In addition, the data suggest that O3 uptake may be principally localized to the conducting airways.
Postlethwait
E M
EM
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0876.
Langford
S D
SD
Bidani
A
A
D000042:Absorption; D000280:Administration, Inhalation; D000818:Animals; D004848:Epithelium / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010126:Ozone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013696:Temperature
D010126:Ozone