EVOLUTION OF ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN THE RAT

To clarify the evolution of acute lung injury induced by endotoxin, th e progression of lung damage in 26 rats submitted to intratracheal ins tillation of 5 mg/kg body weight endotoxin was examined by blood gas a nalysis, computerized tomography, light and electron microscopy. Hyper aemia, hypercapnia, acidosis and inhomogeneous bilateral infiltrates d eveloped gradually within 48 hours. Monocytes appeared within blood ca pillaries and the instertitium by 12 hours after treatment, then migra ted into alveoli and underwent progressive differentiation into macrop hages by 24 hours after treatment. Granulocytes were found within bloo d capillaries at an early stage, but outside capillaries only at 48 ho urs. Hyperplasia of type II pneumocytes and hypertrophy of interstitia l fibroblasts also occurred at 48 hours. These data suggest that the p athogenesis of endotoxin induced pulmonary injury proceeds through an early phase of granulocyte migration inside capillaries and monocyte e xtravasation, an intermediate phase of monocyte differentiation into m acrophages inside alveoli and a late phase of diffuse infiltration of alveoli by newly differentiated macrophages and late-extravasated neut rophils.