title: Decay-accelerating factor limits hemorrhage-instigated tissue injury and improves resuscitation clinical parameters.
abstract: BACKGROUND
  Complement is invariably activated during trauma and contributes to tissue injury. Recombinant human decay-accelerating factor (DAF), a complement regulatory protein that inhibits both classical and alternative pathways, improves survival and reduces tissue damage in animal models of tissue injury. The extent to which DAF may facilitate resuscitation in hemorrhaged large animals is not known.
  
  
  METHODS
  Male Yorkshire swine assigned to one of six groups were subjected to controlled, isobaric hemorrhage over 15 min to a target mean arterial pressure (MAP) of 35 mm Hg. Hypotension was maintained for 20 min followed by a bolus intravenous injection of DAF or vehicle followed by Hextend resuscitation. Animals were observed for 3 h after hypotensive Hextend resuscitation. Survival, blood chemistry, and physiological parameters were recorded. Additionally, tissue from lung, small intestine, liver, and kidney were subjected to histopathologic evaluation and tissue deposition of complement proteins was determined by immunohistochemistry, dot-blot, and Western blot analyses.
  
  
  RESULTS
  Administration of DAF (25 μg/kg) to animals subjected to hemorrhage prior to Hextend infusion significantly improved survival (73% versus 27%); protected gut, lung, liver, and kidney tissue from damage; and resulted in reduced resuscitation fluid requirements when compared with animals subjected to hemorrhage and resuscitation with Hextend alone. Animals treated with a higher dose of DAF (50 μg/kg) followed by Hextend fluid resuscitation did not experience the same benefit, suggesting a narrow therapeutic range for use of DAF as adjunct to Hextend fluid.
  
  
  CONCLUSIONS
  DAF improved survival and reduced early Hextend fluid resuscitation requirements in swine subjected to hemorrhagic shock. These benefits are attributed to decreased complement deposition and limited organ damage.
authors.affiliation: Immunomodulation of Trauma Program, US Army Institute of Surgical Research, San Antonio, Texas, USA. jurandir.dallelucca@us.army.mil
authors.forename: Jurandir J
authors.initials: JJ
authors.lastname: Dalle Lucca
authors.forename: Yansong
authors.initials: Y
authors.lastname: Li
authors.forename: Milomir O
authors.initials: MO
authors.lastname: Simovic
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Slack
authors.forename: Andrew
authors.initials: A
authors.lastname: Cap
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Falabella
authors.forename: Michael
authors.initials: M
authors.lastname: Dubick
authors.forename: Frank
authors.initials: F
authors.lastname: Lebeda
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005440:Fluid Therapy; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000401:mortality; D015996:Survival Rate; D013552:Swine; D016896:Treatment Outcome
chemical_list: D018958:CD55 Antigens; D006895:Hydroxyethyl Starch Derivatives