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Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1.

Abstract
We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan 1 and that the early use of fresh frozen plasma (FFP) in these patients is correlated with improved clinical outcomes. As the lungs are frequently injured after trauma, we hypothesized that hemorrhagic shock-induced shedding of syndecan 1 exposes the underlying pulmonary vascular endothelium to injury resulting in inflammation and hyperpermeability and that these effects would be mitigated by FFP. In vitro, pulmonary endothelial permeability, endothelial monolayer flux, transendothelial electrical resistance, and leukocyte-endothelial binding were measured in pulmonary endothelial cells after incubation with equal volumes of FFP or lactated Ringer's (LR). In vivo, using a coagulopathic mouse model of trauma and hemorrhagic shock, pulmonary hyperpermeability, neutrophil infiltration, and syndecan 1 expression and systemic shedding were assessed after 3 h of resuscitation with either 1× FFP or 3× LR and compared with shock alone and shams. In vitro, endothelial permeability and flux were decreased, transendothelial electrical resistance was increased, and leukocyte-endothelial binding was inhibited by FFP compared with LR-treated endothelial cells. In vivo, hemorrhagic shock was associated with systemic shedding of syndecan 1, which correlated with decreased pulmonary syndecan 1 and increased pulmonary vascular hyperpermeability and inflammation. Fresh frozen plasma resuscitation, compared with LR resuscitation, abrogated these injurious effects. After hemorrhagic shock, FFP resuscitation inhibits endothelial cell hyperpermeability and inflammation and restores pulmonary syndecan 1 expression. Modulation of pulmonary syndecan 1 expression may mechanistically contribute to the beneficial effects FFP.
AuthorsZhanglong Peng, Shibani Pati, Daniel Potter, Ryan Brown, John B Holcomb, Raymond Grill, Kathryn Wataha, Pyong Woo Park, Hasen Xue, Rosemary A Kozar
JournalShock (Augusta, Ga.) (Shock) Vol. 40 Issue 3 Pg. 195-202 (Sep 2013) ISSN: 1540-0514 [Electronic] United States
PMID23807246 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Syndecan-1
Topics
  • Animals
  • Cells, Cultured
  • Endothelium (metabolism)
  • Humans
  • Leukocytes (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plasma
  • Pneumonia (metabolism, therapy)
  • Shock, Hemorrhagic (metabolism, therapy)
  • Syndecan-1 (metabolism)

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