title: Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage.
abstract: BACKGROUND
  Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model.
  
  
  METHODS
  Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2'-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage.
  
  
  RESULTS
  No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24).
  
  
  CONCLUSIONS
  Resuscitation with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.
authors.affiliation: Department of Surgery, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Philbert Y
authors.initials: PY
authors.lastname: Van
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hamilton
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kremenevskiy
authors.forename: Chitra
authors.initials: C
authors.lastname: Sambasivan
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Spoerke
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Differding
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Watters
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004249:DNA Damage / Q000187:drug effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D009104:Multiple Trauma / Q000097:blood / Q000150:complications*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010949:Plasma; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000150:complications / Q000235:genetics / Q000628:therapy*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D016207:Cytokines; D001205:Ascorbic Acid