• Bolin Cai, Fei Chen, Xingchun Lin, Edmund Miller, Csaba Szabo, Edwin A Deitch, Edwin A Deithch, and Lusi Ulloa.
• Laboratory of Anti-inflammatory Signaling and Surgical Immunology, University of Medicine and Dentistry of New Jersey, USA.
• Crit. Care Med. 2009 Mar 1; 37 (3): 860-8.

ObjectivesSevere 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.DesignLaboratory animal experiments.SettingAnimal research laboratory at university medical school.SubjectsAdult male Sprague-Dawley rats.InterventionsLethal 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.ResultsResuscitation 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.ConclusionsEP may be a promising anti-inflammatory supplement to improve survival during resuscitation in critical care.

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