title: Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock.
abstract: BACKGROUND
  Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown.
  
  
  METHODS
  Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals.
  
  
  RESULTS
  No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p < 0.05), but less so at 2 hours in the AA group compared with CA and HCl.
  
  
  CONCLUSIONS
  In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.
authors.affiliation: Division of Trauma, Critical Care & Acute Care Surgery, Department of Surgery, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hamilton
authors.forename: Philbert Y
authors.initials: PY
authors.lastname: Van
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Differding
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kremenevskiy
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Spoerke
authors.forename: Chitra
authors.initials: C
authors.lastname: Sambasivan
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Watters
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005612:Freeze Drying; D007249:Inflammation / Q000097:blood / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D010949:Plasma; D016133:Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001205:Ascorbic Acid