Respiratory mechanics in conscious sheep: response to methacholine

Most currently used animal models of allergic airway diseases differ from human asthma in that induced bronchospasm in the former is not accompanied by pulmonary hyperinflation. In the present investigation, we chose unsedated, restrained sheep to determine the effect of cholinergic bronchial provocation on respiratory mechanics, functional residual capacity (FRC), and arterial blood gases. Seven animals had been actively sensitized by intramuscular injections of Ascaris suum extract, and four untreated animals served as controls. After inhalation of nebulized 1% methacholine solution, mean pulmonary resistance increased significantly in the sensitized sheep from a base line of 2.4 +/- 0.7 (SD) cmH2O/(l/s) to a peak value after 5 min of 7.9 +/- 4.0 cmH2O/(l/s). This was accompanied by a significant increase of mean FRC from 0.99 +/- 0.14 liters to 1.31 +/- 0.24 liters. The observed changes were transient, and after 60 min, pulmonary resistance and FRC had returned to base-line values. No significant changes occurred in static lung compliance, PaO2, PaCO2, and pH. In the control animals, methacholine provocation did not produce changes in pulmonary function. These results indicate that, in sensitized conscious sheep, induced bronchospasm is associated with pulmonary hyperinflation.