A. Castiello et al., DEPLETION OF SURFACTANT TUBULAR MYELIN WITH PULMONARY DYSFUNCTION IN A RAT MODEL FOR ACUTE ENDOTOXEMIA, Shock, 2(6), 1994, pp. 427-432
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.