Alveolar epithelial injury causing respiratory distress in dogs: physiologic and electron-microscopic correlations

Structural and mechanical changes were correlated in 29 dogs with acute alveolar injury induced by the subcutaneous administration of N-nitroso-N-methylurethane (NNNMU). The injury was characterized by necrosis and repair of alveolar epithelium while the vascular endothelium remained essentially intact. Compliance of the lung (CL) decreased and elastic recoil increased as epithelial necrosis occurred. During recovery, improved elastic recoil coincided with epithelial regeneration, although CL remained abnormal. The late phase was characterized histologically by widespread closure of clusters of alveoli alternating with dilated small air spaces. The process resulted in distortion of lung architecture and resembled interstitial fibrosis. Reduced lung volume and decreased distensibility of dilated small air spaces may have accounted for the persistently abnormal CL. Because of the specific site of anatomic involvement, the predictable evolution of deranged lung mechanics, and the similarity to human lung injury (adult respiratory distress syndrome), the lung injured by administration of N-nitroso-N-methylurethane is a suitable model to study pathophysiology and types of therapy in a controlled setting.