title: Alpha1-acid-glycoprotein protects against trauma-hemorrhagic shock.
abstract: BACKGROUND
  Recent studies have shown that the acute phase protein alpha(1)-acid-glycoprotein (AAG) directly modifies endothelial cell responsiveness and is a crucial factor for maintaining endothelial barrier function. We hypothesized that the addition of AAG to the resuscitation fluid will prevent edema formation, increases circulating blood volume, and reduces tissue inflammation following soft tissue trauma and hemorrhagic shock.
  
  
  METHODS
  Male Sprague-Dawley rats (338 +/- 28 g) underwent a 5-cm midline laparotomy (i.e., induction of soft tissue trauma) and were bled to and maintained at a mean arterial pressure of 35 mm Hg for 90 min. The rats were then resuscitated with four times the shed blood volume with Ringer's lactate containing 200 mg/kg AAG or the same amount of albumin. At 6 h after resuscitation, organ wet-to-dry weight ratios and circulating blood volume (Evans blue dilution) were determined. Neutrophil accumulation (myeloperoxidase activity, MPO) and tissue lipid peroxidation (thiobarbituric acid reactive substances) were also measured in the lungs, liver, and intestine.
  
  
  RESULTS
  Administration of AAG during the resuscitation significantly increased circulating blood volume and reduced edema formation, neutrophil accumulation, and lipid peroxidation. Interestingly, concomitant plasma IL-6 levels increased while TNF-alpha levels were not significantly affected.
  
  
  CONCLUSIONS
  Since addition of AAG to the resuscitation fluid increased circulating blood volume, reduced edema formation, and neutrophil accumulation following trauma and hemorrhagic shock, supplementation of this acute phase protein appears to be a potential adjunct to prevent capillary leakage in patients undergoing major traumatic injury.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294-0019, USA.
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Kuebler
authors.forename: Balazs
authors.initials: B
authors.lastname: Toth
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Loring W
authors.initials: LW
authors.lastname: Rue
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007552:Isotonic Solutions / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009961:Orosomucoid / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D007552:Isotonic Solutions; D009961:Orosomucoid; D000077325:Ringer's Lactate; D017392:Thiobarbituric Acid Reactive Substances; D000637:Transaminases