[Morphologic and biochemical kinetics of the pathogenesis of acute lung injury by endotoxin in rats]. / Cinetica morfologica e biochimica della patogenesi del danno polmonare acuto da endotossina nel ratto.

BACKGROUND AND AIM: To highlight the intervention sequence of cells and their products (RO degree and NO) involved in the pathogenesis of lung injury caused by the instillation of endotoxin in rats. EXPERIMENTAL DESIGN: An experimental comparative study in rats. MATERIALS AND METHODS: The experiments were performed using intratracheal instillation of endotoxin in rats (5 mg/kg in 0.125 ml of saline solution). Untreated rats or those instilled with saline solution alone formed the control group. All animals were sacrificed 12, 24 and 48 hours after instillation and the following studies were performed on both lungs: 1) morphological study (optical and electronic); 2) assay of lung MDA; 3) NADPH-diaphorase evaluation using a histochemical method. RESULTS: Lung damage evolves gradually over 48 hours. After the first 12 hours, neutrophil granulocytes were present in the lung capillaries together with monocytes; monocytes were also present in the interstitium. During the following hours, monocytes differentiated into macrophages and, once activated, the granulocytes passed into the interstitium. The parenchyma appears to be extensively altered. Tissular MDA gradually increases until it reaches a maximum level (p < 0.01 vs basal) at 48 hours. Positivity for NADPH-d in macrophage and/or fibroblastic cells was evident after 24 hours and increased after 48 hours. CONCLUSIONS: Acute lung injury caused by endotoxin involves both NO and RO degree. Their production is related to different cell types and follows slightly different kinetic.

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.