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.