Augmentation of elastase-induced emphysema by cigarette smoke. Description of a model and a review of possible mechanisms.

Rats were treated with a single endotracheal dose of purified porcine pancreatic elastase (400 IU/kg), exposed to undiluted cigarette smoke from Kentucky 2RI reference cigarettes (one 35-ml puff/min for 10 min daily, 5 days per week, for 12 wk) or with a combination of elastase followed by smoke exposure. A number of significant functional abnormalities were observed in the lungs of rats receiving elastase; these included reduced spontaneous ventilation, enlarged subdivisions of lung volume, loss of elastic recoil, and diminished gas exchange capacity. Rats receiving both elastase and cigarette smoke had significantly more severe pulmonary dysfunction than did rats treated with elastase alone. Morphometric measurements of mean linear intercept demonstrated a loss of alveolar fine structure, with enlargement of distal air spaces in elastase-treated rats. These changes were significantly more severe in rats treated with both elastase and cigarette smoke. Pulmonary function tests and morphometric measurements in sham-treated rats and in rats exposed to cigarette smoke only were not significantly different from those in untreated control animals. It is concluded that elastase-induced emphysema in rats is enhanced by exposure to whole cigarette smoke.