Effect of respiratory pattern on ozone injury to the airways of isolated rat lungs

Ozone stimulates the "defensive" C-fibers in the lungs, changing breathing pattern to rapid and shallow. Ne hypothesized that when ozone is administer ed to the isolated lung with a rapid shallow breathing pattern rather than a slow deep pattern, relatively less airway epithelial damage would occur. Four groups of isolated buffer perfused rat lungs were exposed to ozone (1 ppm) or to filtered air for 90 min with either a slow deep (SDB, tidal volu me 2.4 mi, frequency 40 breaths/min) or a rapid shallow breathing pattern ( RSB, tidal volume 1.2 ml, frequency 80 breaths/min), resulting in an equiva lent inspired dose. The absorbed dose of ozone did not differ between the e xposed groups. Ethidium homodimer-l was then instilled into the trachea to identify injured airway epithelial cells. The lungs were fixed, the airways were microdissected, and the airway epithelial cells were counterstained w ith YPRO-1 prior to evaluation with confocal microscopy. Ozone-induced airw ay epithelial cell injury occurred to a lesser overall degree when lungs we re exposed by the RSB pattern (p = 0.003). The relative reduction in injury was greater (p < 0.05) in the proximal axial airway than in its adjacent a irway branch and terminal bronchioles. Ozone induced an increase in pulmona ry resistance with the SDB pattern but not with the RSB pattern. Thus, at a n equivalent dose of inspired ozone, a RSB pattern resulted in less total d amage than a SDB pattern and the distribution of protection was heterogeneo us with proximal axial airways displaying the greatest relative reductions in epithelial damage, (C) 2000 Academic Press.