Assessment of elastase-induced structural and functional changes in sheep lungs.

A large-animal model of elastase-induced emphysema is being developed, which permits the evaluation of corresponding changes in lung structure and function under controlled conditions. Varying doses of elastase were instilled intrabronchially into the lower right lobes of 12 sheep. Changes in regional distribution of lung perfusion (Q) and ventilation (V), corrected for lung volume, were determined from in vivo measurements with radioactive Tc-99m MAA, Kr-81m and Xe-127, respectively, before and four weeks after elastase treatment. Lung injury was assessed by histological examinations of tissue removed post mortem. A positive correlation (r = 0.74; p less than 0.01) was observed between the dose of instilled elastase (range: 800-8,000 units) and a reduction in Q. A decrease in Q also correlated significantly (r = 0.63; p less than 0.05) with an increase in alveolar mean linear intercept (Lm). V also decreased with increasing dose of elastase and with increasing Lm, but the results did not attain statistical significance. These results suggest that computer analysis of regional Q and V by radionuclide imaging techniques represents a reliable, sensitive and non-invasive means of assessing elastase-induced pulmonary injury in the sheep.