Tissue factor in experimental acute lung injury.

Published

Journal Article (Review)

Acute lung injury (ALI) is characterized by fibrin deposition in the tissue and vascular spaces. Coagulation is activated after exposure to endotoxin or bacteria, and a procoagulant environment rapidly develops in the vascular, interstitial, and alveolar spaces of the lung. These changes are tissue factor (TF)-dependent and associated with increases in inflammatory cytokines. Procoagulant changes also occur in the lungs of patients with the acute respiratory distress syndrome (ARDS), suggesting that epithelial inflammation activates the extrinsic pathway. Many inflammatory mediators have specific effects on coagulation; however, the role of TF in regulation of pulmonary inflammatory responses is less clear. Here we report initial data on blockade of TF-initiated coagulation in baboons with Escherichia coli sepsis-induced ALI, using active site-inactivated FVIIa (FVIIai ASIS). Treatment with FVIIai prevented plasma fibrinogen depletion and attenuated fibrin deposition in the tissues. The drug also decreased systemic cytokine responses and inflammatory changes in the lung, including neutrophil infiltration, and decreased edema. Coagulation blockade with FVIIai improved lung function by preserving gas exchange and compliance, decreased pulmonary hypertension, and enhanced renal function. These results show that TF-FVIIa complex is an important regulatory site for the pathologic response of the lung to sepsis.

Full Text

Duke Authors

Cited Authors

  • Welty-Wolf, KE; Carraway, MS; Idell, S; Ortel, TL; Ezban, M; Piantadosi, CA

Published Date

  • October 1, 2001

Published In

Volume / Issue

  • 38 / 4 Suppl 12

Start / End Page

  • 35 - 38

PubMed ID

  • 11735108

Pubmed Central ID

  • 11735108

International Standard Serial Number (ISSN)

  • 0037-1963

Language

  • eng

Conference Location

  • United States