Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage

Bolin Cai, Fei Chen, Xingchun Lin, Edmund Miller, Csaba Szabo, Edwin A. Deithch, Lusi Ulloa

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

OBJECTIVES:: 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. DESIGN:: Laboratory animal experiments. SETTING:: Animal research laboratory at university medical school. SUBJECTS:: Adult male Sprague-Dawley rats. INTERVENTIONS:: 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 IκBα activation. CONCLUSIONS:: EP may be a promising anti-inflammatory supplement to improve survival during resuscitation in critical care.

Original languageEnglish (US)
Pages (from-to)860-868
Number of pages9
JournalCritical Care Medicine
Volume37
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

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Keywords

  • Ethyl pyruvate
  • Hemorrhage
  • High mobility group B protein-1
  • Inflammation
  • Resuscitation
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Cai, B., Chen, F., Lin, X., Miller, E., Szabo, C., Deithch, E. A., & Ulloa, L. (2009). Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage. Critical Care Medicine, 37(3), 860-868. https://doi.org/10.1097/CCM.0b013e31819b8237