title: Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury.
abstract: Endotoxin stimulus plays a significant role in various forms of acute lung injury (ALI) which may be exacerbated by mechanical ventilation. Here, we identify the temporal pathophysiologic sequence following inhaled lipopolysaccharide (LPS) and subsequently examine both LPS dose and V(T) relationships. Rats received intratracheal LPS (3, 9 or 15 mg/kg) prior to mechanical ventilation (V(T)=6, 9 or 12 ml/kg) and measurement of forced impedance mechanics for up to 4h. LPS-induced lung injury was achieved within the 15 min of LPS instillation with a 78% decrease in PaO(2) promptly followed by approximately 30% deterioration in tissue elastance. Despite a 41% increase in total surfactant, the active disaturated phospholipid fraction decreased 3-7% with decreasing PaO(2) and tissue mechanics and with increases in total lung lavage protein (150%) and wet-to-dry lung weight ratio (10%). V(T)=12 ml/kg resulted in an additional deterioration in tissue resistance (130%) and elastance (63%). These results suggest that LPS-induced lung injury is both LPS dose and V(T) sensitive, supporting a 'two hit' model of ALI.
authors.affiliation: Department of Critical Care Medicine, Flinders University, Adelaide, Australia. dani.dixon@flinders.edu.au
authors.forename: Dani-Louise
authors.initials: DL
authors.lastname: Dixon
authors.forename: Hilde R
authors.initials: HR
authors.lastname: De Smet
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bersten
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000503:physiopathology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*; D013501:Surface-Active Agents / Q000494:pharmacology; D013990:Tidal Volume / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010743:Phospholipids; D013501:Surface-Active Agents