Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury

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 VT relationships. Rats received intratracheal LPS (3, 9 or 15 mg/kg) prior to mechanical ventilation (VT = 6, 9 or 12 ml/kg) and measurement of forced impedance mechanics for up to 4 h. LPS-induced lung injury was achieved within the 15 min of LPS instillation with a 78% decrease in PaO2 promptly followed by ∼30% deterioration in tissue elastance. Despite a 41% increase in total surfactant, the active disaturated phospholipid fraction decreased 3–7% with decreasing PaO2 and tissue mechanics and with increases in total lung lavage protein (150%) and wet-to-dry lung weight ratio (10%). VT = 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 VT sensitive, supporting a ‘two hit’ model of ALI.