PEEP-induced changes in epithelial permeability in inbred mouse strains

Inbred mouse strains have demonstrated a range of susceptibilities to inhaled environmental irritants. C57Bl/6J mice are highly susceptible while C3H/HeJ mice are resistant to ozone exposures, as assessed by lavaged protein. However, lavaged protein reflects a loss of both the endothelial and epithelial barrier. To determine whether basal differences exist in the epithelial barrier, we measured soluble tracer (99mtechnetium-diethylenetriamine pentaacetic acid, 99mTc-DTPA) clearance from the lung in spontaneously breathing, anesthetized mice and mice ventilated with increased lung volume with applied positive end-expiratory pressure (PEEP; 1, 6, or 10 cmH2O). Both strains showed more rapid clearance during ventilation with 10 cmH2O PEEP compared with other ventilation pressures (p < 0.001). There was a substantial difference in clearance between the two strains during ventilation with 10 cmH2O PEEP (mean half time for C57Bl/6J mice = 19 ± 4 min versus 34 ± 3 min for C3H/HeJ mice; p < 0.001). Thus, when lung volume is increased, the susceptible C57Bl/6J strain shows a greater change in epithelial barrier than the resistant C3H/HeJ strain. These results may reflect fundamental differences in lung architecture.