title: Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage.
abstract: OBJECTIVE
  Severe hemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to reestablish tissue perfusion, but they fail to prevent lethal inflammatory responses. Our previous studies indicate that ethyl pyruvate (EP) inhibits tumor necrosis factor (TNF) production from macrophages. Here, we analyze whether EP can provide a therapeutic anti-inflammatory value to resuscitation fluids.
  
  
  METHODS
  Laboratory animal experiments.
  
  
  METHODS
  Animal research laboratory at university medical school.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  Lethal hemorrhage over 15 minutes to reach a mean arterial blood pressure of 35-40 mm Hg and subsequent maintenance of this mean arterial blood pressure for another 15 minutes. Resuscitation was limited to 15 mL/kg Hextend with or without EP.
  
  
  RESULTS
  Resuscitation with Hextend supplemented with EP rescued all the animals from lethal hemorrhage. Unlike conventional fluids, EP inhibited the production of inflammatory and cardiodepressant factors such as TNF and high mobility group B protein-1. From a pharmacologic perspective, resuscitation with EP was particularly effective inhibiting TNF production in the spleen and the heart. Unlike other anti-inflammatory strategies, EP mitigated systemic inflammation through a mechanism independent of the spleen. At the molecular level, EP inhibited both poly(ADP-ribose) polymerase and p65RelA DNA binding without affecting IkappaBalpha activation.
  
  
  CONCLUSIONS
  EP may be a promising anti-inflammatory supplement to improve survival during resuscitation in critical care.
authors.affiliation: Laboratory of Anti-inflammatory Signaling and Surgical Immunology, University of Medicine and Dentistry of New Jersey, USA.
authors.forename: Bolin
authors.initials: B
authors.lastname: Cai
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Xingchun
authors.initials: X
authors.lastname: Lin
authors.forename: Edmund
authors.initials: E
authors.lastname: Miller
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deithch
authors.forename: Lusi
authors.initials: L
authors.lastname: Ulloa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005440:Fluid Therapy; D006470:Hemorrhage / Q000401:mortality* / Q000628:therapy*; D008297:Male; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D015996:Survival Rate
chemical_list: D000893:Anti-Inflammatory Agents; D011773:Pyruvates; C046522:ethyl pyruvate