Article Text

  1. D. O. Burdette1,
  2. S. A. Nonas2,
  3. I. Miller2,
  4. A. A. Birukova1,
  5. S. Chatchavalvanich1,
  6. J. G.N. Garcia1,
  7. K. G. Birukov1
  1. 1 Department of Medicine, The University of Chicago, Chicago, IL;
  2. 2 Department of Medicine, Johns Hopkins University, Baltimore, MD


Purpose of Study Acute lung injury (ALI) is a devastating syndrome characterized by pulmonary inflammation and vascular barrier dysfunction with protein-rich edema. Mechanical ventilation at high tidal volumes can worsen existing ALI and even cause ventilator-induced lung injury (VILI) de novo. Previous studies have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) enhances basal endothelial cell (EC) barrier properties and prevents acute lung inflammation and EC dysfunction in response to bacterial lipopolysaccharide (LPS) via direct Rac-Cdc42-mediated effects on EC cytoskeleton and via competitive inhibition of LPS binding to toll-like receptor 4 (TLR4).

Methods Adult male Brown Norway rats (250-350 g) were ventilated at low tidal volume (LTV, 7 mL/kg) or high tidal volume (HTV, 20 mL/kg) for 2 hours, 85 breaths/min. A subset of animals received intravenous OxPAPC (1.5 mg/kg) at the start of mechanical ventilation. Bronchoalveolar lavage (BAL) cell count and protein concentration were measured as markers of inflammation and vascular permeability. IL-6, IL-1beta, and hyaluronan levels in BAL were quantitatively assessed by enzyme linked immunoabsorbance assays (ELISA).

Results HTV caused a 70% increase in BAL total cell count (p < .05) and a 169% increase in BAL protein (p < .01) compared with controls. OxPAPC reduced HTV-induced elevations in total cell count (41% decrease versus HTV alone) and protein (42% decrease versus HTV alone). HTV also caused an increase in the hyaluronan levels found in BAL samples, which was completely abrogated by intravenous injection of OxPAPC. HTV also caused a 223% increase in the IL-6 levels in BAL samples as compared to controls, which was attenuated by OxPAPC treatment (130% versus control, p < .05). HTV had only a modest effect on IL-1beta up-regulation (45% increase versus control), which still was attenuated by OxPAPC treatment (27% increase versus control). Conclusion: These studies demonstrate for the first time the protective effect of membrane-derived oxidized phospholipids on ventilator-induced lung inflammation and barrier dysfunction.

HL75349, HL76259, HL58064.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.