PEEP-induced changes in epithelial permeability in inbred mouse strains.

ABSTRACT

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 ((99m)technetium-diethylenetriamine pentaacetic acid, (99m)Tc-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 10cmH(2)O). Both strains showed more rapid clearance during ventilation with 10cmH(2)O PEEP compared with other ventilation pressures (p<0.001). There was a substantial difference in clearance between the two strains during ventilation with 10cmH(2)O PEEP (mean half time for C57Bl/6J mice=19+/-4min versus 34+/-3min 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.