Respiratory Distress Syndrome is exemplified by inflammation, loss of surfactant function and collapse of pulmonary alveoli. Models in adult rabbits that combine these features will be employed to assess an experimental method of treatment. The method involves lavaging with dilute surfactant to remove inflammatory exudate, restore pulmonary function and prevent recurrence of inflammation, The proposed studies will interdigitate with a parallel Clinical Trial (IND 46,164) in which dilute KL4-Surfactant will be used as a lavage in human beings with ARDS. In the current project adult rabbits will develop pulmonary injury after removal of intrinsic surfactant and intratracheal instillation of LPS or after aspiration of dilute HC1. The resulting inflamed ateelectatic lung will receive treatment with surfactant given by bolus instillation or by lavage with dilute surfactant, or, as control, saline. The study will focus on (1) removal of pulmonary exudate, improvement of pulmonary function and inhibition of recurrence of the inflammation; (2) stability of alveolar expansion and the effect of specific inhibition of inflammatory mediators on the pulmonary injury when administered in the alveolar microenvironment; (4) the role of IL-8 in the development of the pulmonary inflammation. The data obtained will be applied to understanding the results emerging from the ongoing Clinical Trial.
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