DEPLETION OF SURFACTANT TUBULAR MYELIN WITH PULMONARY DYSFUNCTION IN A RAT MODEL FOR ACUTE ENDOTOXEMIA

Although prolonged Gram-negative sepsis with high permeability alveola r edema, a well documented cause of adult respiratory distress syndrom e, has been shown to result in surfactant alterations, the effects of acute endotoxemia on the lung surfactant system are largely unknown. I n this study, lethal endotoxemia (>80% mortality at 24 h) resulting in severe, rapid leukopenia with progressive thrombocytopenia was achiev ed through intraperitoneal injection of adult Fischer 344 rats with 3. 5 mg of Escherichia coli endotoxin/kg. After assessment of pulmonary m echanics under general anesthesia, endotoxin-injected rats and appropr iate controls were killed at 4, 8, and 12 h for morphological and bioc hemical analyses. Morphometric estimation of surfactant membrane subty pes in bronchoalveolar lavage fluid revealed prominent alterations inc luding significant decrease (45%) in tubular myelin 12 h post-endotoxi n, with a threefold increase in lamellar body-like forms at 8 and 12 h . Acute endotoxicosis resulted in decrease of total dynamic compliance , whereas pulmonary resistance remained unchanged. These changes were associated with margination of polymorphonuclear leukocytes in lung mi crocirculation, multifocal septal edema, and decrease in lamellar body lysozyme specific activity at 12 h. Alveolar edema, as determined by measurement of total protein in cell-free bronchoalveolar lavage fluid , was absent in both controls and endotoxin-injected rats. The results indicate that bloodborne lung injury induced by lethal endotoxicosis initiates acute perturbation of secreted surfactant membranes with pul monary dysfunction in the absence of high protein alveolar edema.