Abstract
Elastase-induced emphysema in rodents is characterized by enlarged alveoli and decreased lung elastance but generally no change in airway resistance. We studied airway and tissue mechanics and recruitment in rats before and during constrictor challenge.
Sprague-Dawley rats were treated by intratracheal instillation of 50 U porcine pancreatic elastase (PPE, n=6). Three weeks later, these animals and 6 controls (C) were anesthetized, tracheotomized and mechanically ventilated. From low-frequency impedance (Zrs), Newtonian resistance (RN), tissue damping (G), elastance (H) and hysteresivity (η=G/H) were estimated. The lungs were degassed in vivo with oxygen breathing (10 min) and tracheal occlusion (10 s), and then reinflated to 35 hPa, while the pressure-volume (PV) relationship and intratracheal crackle sound (Cra) were recorded. Measurements of Zrs, PV and Cra were repeated during i.v. infusion of methacholine (Mch) at 64 μg/kg/min.
RN was not different between groups PPE and C at baseline (44±4 vs 46±10 hPa.s/l) and during challenge (165±41 vs 176±37 hPa.s/l). G and H, respectively, were significantly lower in the PPE group compared to the controls (613±57 vs 839±165 hPa/l, and 2273±301 vs 3033±385 hPa/l), although their elevations due to Mch were similar (71±43% vs 79±34% for G, and 24±13% vs 25±20% for H). Whereas cumulative crackle intensity reached 80% at similar P levels in both groups, the recruited volume was more reduced during challenge (-39 vs -16%) in the PPE group.
In summary, while airway resistance and recruitment remained unaffected, the tissue damage was associated with an enhanced tissue constrictor response following elastase treatment.
Supported by grants OTKA 66700 and NIH HL090757.
- © 2011 ERS
