Effect of bronchoconstrictive aerosols on pulmonary gas trapping in the A/J mouse

Abstract

We exposed conscious A/J mice to several challenge aerosols and measured gas trapped within excised lungs by quantitating their buoyancy in saline (Archimedes' principle). The temporal stability of the excised lung gas volume (ELGV) measurement was also examined. ELGV increased in a dose proportional manner with increasing concentrations of methacholine and reached a maximum of 338 ± 33% above vehicle-exposed controls. The A/J mice were 100 times more responsive to aerosol methacholine compared to hyporesponsive C3H/HeJ mice. Aerosol challenges of U-46619, a thromboxane A 2 mimetic, and serotonin resulted in a 40% and 135% increase in ELGV's versus their controls, respectively. ELGV's were not increased after aerosols of leukotriene C 4, histamine, substance P, N-formyl-methionyl-leucyl-phenylalanine and platelet activating factor. Both normal (filtered air-exposed) and hyperinflated (methacholine-exposed) excised lungs lost about 10% of their initial volume by 30 min and 40–65% of initial volume by 4 h. Occlusion of the trachea in either group did not affect the total gas lost, suggesting that the majority of the gas loss was via transpleural diffusion. We conclude that determination of ELGV in mice, when performed soon after challenge testing, is a simple, rapid and reliable estimate of airway obstruction.