Evolution of endotoxin induced acute lung injury in the rat.

To clarify the evolution of acute lung injury induced by endotoxin, the progression of lung damage in 26 rats submitted to intratracheal instillation of 5 mg/kg body weight endotoxin was examined by blood gas analysis, computerized tomography, light and electron microscopy. Hypoxaemia, hypercapnia, acidosis and inhomogeneous bilateral infiltrates developed gradually within 48 hours. Monocytes appeared within blood capillaries and the instertitium by 12 hours after treatment, then migrated into alveoli and underwent progressive differentiation into macrophages by 24 hours after treatment. Granulocytes were found within blood capillaries at an early stage, but outside capillaries only at 48 hours. Hyperplasia of type II pneumocytes and hypertrophy of interstitial fibroblasts also occurred at 48 hours. These data suggest that the pathogenesis of endotoxin induced pulmonary injury proceeds through an early phase of granulocyte migration inside capillaries and monocyte extravasation, an intermediate phase of monocyte differentiation into macrophages inside alveoli and a late phase of diffuse infiltration of alveoli by newly differentiated macrophages and late-extravasated neutrophils.