Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of emphysema
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Thin-slice videomicroscopy was used to examine the kinetics of constriction in small airways in situ. Balb/C mice inhaled elastase (0-20 IU), and were then left to recover for 14 days before euthanisation and lung removal. Cholinergic responsiveness was assessed in thin lung slices. Magnitude and velocity of narrowing in response to 10(-5) M acetylcholine (ACh), as well as the full concentration-response relationship for ACh (10(-8)-10(-5) M) were assessed. In vivo exposure to elastase was accompanied by statistically significantly decreased magnitudes and velocities of contraction, but no change in the ACh concentration-response relationship. Conversely, overnight, in vitro exposure of slices from control animals to elastase (2.5 microg.mL(-1)) resulted in increased magnitudes and velocities of airway narrowing, with impaired relaxation, as well as marked tearing of the airways from the surrounding parenchyma. These changes are characteristic of decreased tethering forces on the airway wall. Thus, the lung slice technique coupled with videomicroscopic analysis of airway contraction velocities provides a powerful tool to study airway-parenchymal interactions. The elastolytic model of emphysema, which manifests with airspace enlargement and loss of parenchymal attachments, is accompanied by decreased airway contraction kinetics. The mechanism(s) underlying this loss of function remain to be elucidated.
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