The disease has multiple causes, such as sepsis, injury, and toxic inhalants.
Pulmonary surfactant is degraded during the inflammatory process, and the lungs collapse.
A rabbit model that mimics the human disease has been developed in which pulmonary injury is produced by instillation of bacterial lipopolysaccharide followed in 3 hours by a second stimulus such as phorbol myristate acetate. These enzymes are found in the human disease as well. Their presence in the alveolar space is associated with protein transudation through blood vessel walls, the nonselective leakage of molecules up to 700,000 molecular weight, and loss of basement membrane proteins and peptides into the alveolar space, suggesting proteolytic cleavage of the sievelike vascular basement membrane. Two distinct inhibitors of these enzymes will be used to block the nonselective protein leakage in blood vessels. The potential protective effect on surfactant and pulmonary function will be assessed.