INTRATRACHEAL AEROSOLIZATION OF ENDOTOXIN (LPS) IN THE RAT - A COMPREHENSIVE ANIMAL-MODEL TO STUDY ADULT (ACUTE) RESPIRATORY-DISTRESS SYNDROME

The aim of the study was to extend existing evidence that intratrachea l aerosolization of LPS may serve as a very relevant model to study AR DS. The authors investigated the sequence of pathogenic events reflect ed by changes in levels of tumor necrosis factor alpha (TNF alpha), su rfatant-associated protein A (SP-A) in BAL fluid, in addition to cell count, edema formation, and respiratory function. Within 24 h followin g intratracheal aerosolization of LPS in the rat, ARDS could be diagno sed according to the lung injury score for patients. This score includ es the extent of the inflammatory density on chest X-rays, the severit y of hypoxemia, the decline in lung compliance, and the level of PEEP (positive end expiratory pressure). In addition, other typical feature s of human ARDS appeared to be present in this model: (1) increased mi crovascular permeability reflected by edema, elevated levels of protei n and of LDH, and increased numbers of PMNs in BAL fluid; (2) high lev els of TNF alpha in BAL fluid preceding the appearance of PMNs; (3) ch anges in breathing pattern and a gradual development of respiratory fa ilure with decreased compliance. SP-A levels in BAL fluid doubled with in one hour after LPS administration, suggesting that this collectiong may play a role in the immediate inflammatory response. Taken togethe r, the findings presented here suggest that intratracheal LPS administ ration mimics the clinical development of ARDS very closely.