Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage.
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.
Cai
Bolin
B
Laboratory of Anti-inflammatory Signaling and Surgical Immunology, University of Medicine and Dentistry of New Jersey, USA.
Chen
Fei
F
Lin
Xingchun
X
Miller
Edmund
E
Szabo
Csaba
C
Deitch
Edwin A
EA
Deithch
Edwin A
EA
Ulloa
Lusi
L
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
D000893:Anti-Inflammatory Agents; D011773:Pyruvates; C046522:ethyl pyruvate