EFFECT OF BRONCHOCONSTRICTIVE AEROSOLS ON PULMONARY GAS TRAPPING IN THE A J MOUSE/

We exposed conscious A/J mice to several challenge aerosols and measur ed 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 i n a dose proportional manner with increasing concentrations of methach oline and reached a maximum of 338 +/- 33% above vehicle-exposed contr ols. The A/J mice were 100 times more responsive to aerosol methacholi ne compared to hyporesponsive C3H/HeJ mice. Aerosol challenges of U-46 619, a thromboxane A(2) mimetic, and serotonin resulted in a 40% and 1 35% increase in ELGV's versus their controls, respectively. ELGV's wer e not increased after aerosols of leukotriene C-4, histamine, substanc e P, N-formyl-methionyl-leucyl-phenyl-alanine and platelet activating factor. Both normal (filtered air-exposed) and hyperinflated (methacho line-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 i n either group did not affect the total gas lost, suggesting that the majority of the gas loss was via transpleural diffusion. We conclude t hat determination of ELGV in mice, when performed soon after challenge testing, is a simple, rapid and reliable estimate of airway obstructi on.