title: Endotoxin induces respiratory failure and increases surfactant turnover and respiration independent of alveolocapillary injury in rats.
abstract: Although endotoxin-induced acute lung injury is associated with inflammation, alveolocapillary injury, surfactant dysfunction, and altered lung mechanics, the precise sequence of these changes is polemic. We have studied the early pathogenesis of acute lung injury in spontaneously breathing anesthetized rats after intravenous infusion of Salmonella abortus equi endotoxin. The animals became hypoxic, and airway resistance, tissue resistance, lung elastance, and static compliance all deteriorated well before any change in alveolar neutrophils, macrophages, lung fluid (99mTc-labeled diethylenetriamine pentaacetic acid), or 125I-albumin flux, which were only appreciably increased at 8.5 hours. Lung elastance deteriorated before airway resistance, indicating that the compliance change was specific rather than caused by reduced lung volume. The subcellular and alveolar content of surfactant proteins A and B, cholesterol, disaturated phospholipids, and phospholipid classes remained normal in the face of a dramatic increase in the synthesis and turnover of 3H-disaturated phosphatidylcholine. Our findings indicate that the increase in surfactant disaturated phospholipid turnover reflects, at least in part, an approximately five-fold increase in "sigh frequency." We suggest that endotoxin has direct effects on tissue resistance and lung elastance independent of surfactant composition and that the initial respiratory failure results primarily from endotoxin-induced ventilation/perfusion mismatch independent of edema or alveolocapillary injury per se.
authors.affiliation: Department of Human Physiology, School of Medicine, Flinders University, South Australia, Australia.
authors.forename: Kate G
authors.initials: KG
authors.lastname: Davidson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bersten
authors.forename: Heather A
authors.initials: HA
authors.lastname: Barr
authors.forename: Kay D
authors.initials: KD
authors.lastname: Dowling
authors.forename: Terence E
authors.initials: TE
authors.lastname: Nicholas
authors.forename: Ian R
authors.initials: IR
authors.lastname: Doyle
mesh_terms: D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001784:Blood Gas Analysis; D015824:Blood-Air Barrier / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000503:physiopathology*; D015656:Respiratory Mechanics; D012475:Salmonella; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D004731:Endotoxins; D011663:Pulmonary Surfactants