Airway wall dimensions during carbachol-induced bronchoconstriction in rabbits

Airway wall area is an important determinant of airway narrowing. We hypothesized that in cross-sectioned peripheral airways, the wall area internal to the outer smooth muscle border (inner wall area) would decrease and the airway wall area external to the outer smooth muscle layer (adventitial area) would increase during bronchoconstriction because of the relocation of blood and/or fluid between these compartments. To test this hypothesis, we used anesthetized open-chest rabbits and measured airway wall dimensions and smooth muscle shortening of membranous airways after carbachol-induced bronchoconstriction using morphometric techniques. Acute (3-min) and sustained (40-min) bronchoconstriction was induced by aerosol nebulization of carbachol and compared with saline treatment. After physiological measurements, the heart base was snared, and the lung and heart were excised en bloc and frozen by using liquid nitrogen while a transpulmonary pressure of 2 cmH2O was maintained. The lung was processed for light-microscopic examination by using a freeze substitution technique. Results show that adventitial area was significantly decreased after sustained but not acute bronchonconstriction. The mechanism of this change, which contradicts our hypothesis, is unclear. However, the decrease of adventitial area could increase rather than decrease the effect of lung parenchymal tethering and attenuate airway narrowing.