title: Depletion of surfactant tubular myelin with pulmonary dysfunction in a rat model for acute endotoxemia.
abstract: Although prolonged Gram-negative sepsis with high permeability alveolar edema, a well documented cause of adult respiratory distress syndrome, has been shown to result in surfactant alterations, the effects of acute endotoxemia on the lung surfactant system are largely unknown. In this study, lethal endotoxemia (> 80% mortality at 24 h) resulting in severe, rapid leukopenia with progressive thrombocytopenia was achieved through intraperitoneal injection of adult Fischer 344 rats with 3.5 mg of Escherichia coli endotoxin/kg. After assessment of pulmonary mechanics under general anesthesia, endotoxin-injected rats and appropriate controls were killed at 4, 8, and 12 h for morphological and biochemical analyses. Morphometric estimation of surfactant membrane subtypes in bronchoalveolar lavage fluid revealed prominent alterations including significant decrease (45%) in tubular myelin 12 h post-endotoxin, 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 microcirculation, 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 pulmonary dysfunction in the absence of high protein alveolar edema.
authors.affiliation: Department of Pathology, University of South Florida Health Science Center, Tampa, USA.
authors.forename: A
authors.initials: A
authors.lastname: Castiello
authors.forename: J F
authors.initials: JF
authors.lastname: Paterson
authors.forename: S A
authors.initials: SA
authors.lastname: Shelley
authors.forename: E M
authors.initials: EM
authors.lastname: Haller
authors.forename: J U
authors.initials: JU
authors.lastname: Balis
mesh_terms: D000208:Acute Disease; D000818:Animals; D001688:Biological Products; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009113:Muramidase / Q000378:metabolism; D009186:Myelin Sheath; D011506:Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D014115:Toxemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001688:Biological Products; D004731:Endotoxins; D011506:Proteins; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; C018167:tubular myelin; C044101:endotoxin, Escherichia coli; D009113:Muramidase