Abstract
Mechanical forces have been suggested to accelerate the deterioration of lung structure and function in emphysema. To test this, we used C57BL/6 mice treated with porcine pancreatic elastase (N=48) or left intact as controls (N=16). At 2, 7 or 21 days after treatment, mice were ventilated (Vt=8 ml/kg, 240/min) for 1 h with or without deep inspirations (DI, inflation to 35 hPa airway pressure twice/min). FRC was measured in a plethysmograph and tissue elastance (H) was calculated from respiratory impedance. After the experiment, lungs were fixed at 20 hPa pressure and sections were stained with hematoxylin-eosin or a modified Verhoeff method to visualize elastin. Independent of time, DI increased FRC (p<0.001) and independent of DI, FRC increased with time (p<0.001). Compared to control, H decreased in the no-DI 7- and 21-day groups (p<0.001, p=0.009). Compared to no-DI, H decreased in the DI groups (p<0.001). DI had a significant effect on FRC and H in controls. Alveoli were grouped as small, medium and large airspaces according to their equivalent diameters (D). DI reduced D of the small airspaces in the 21-day group (p<0.001) suggesting that as the DIs rupture a septal wall, many small airspaces surrounding the newly formed larger airspace reduce their size. The coefficient of variation of elastin increased with time in treated groups (p<0001) reflecting heterogeneous remodeling, but this was not affected by DIs. Our results suggest that acute mechanical forces rupture septal walls with a subsequent increase in FRC and a decrease in small airspace diameters in a time dependent manner during disease progression.
Supported by grants NIH HL090757 and OTKA 66700.
- © 2011 ERS