Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. I. The association of disordered airway physiology to leukocyte infiltration.
We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.