Document Detail


Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.
MedLine Citation:
PMID:  19953001     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate. Resuscitation with ethyl pyruvate did not improve early hemodynamics but prevented hyperglycemia, the intrinsic coagulation pathway, serum aspartate aminotransferase, and myeloperoxidase in the major organs. Resuscitation with ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and high-mobility group B protein 1 levels. Ethyl pyruvate inhibited nuclear factor [kappa]B in the spleen but not in the other major organs. In contrast, ethyl pyruvate inhibited NO in all the major organs, and it also inhibited TNF production in the major organs but in the lung and heart. The most significant effects were found in the terminal ileum where ethyl pyruvate inhibited cytokine production, restrained myeloperoxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial endotoxin. Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic nuclear factor [kappa]B, restrain inflammatory responses, and prevent hyperglycemia, the intrinsic coagulation pathway, and organ injury in porcine hemorrhage without trauma.
Authors:
WeiHong Dong; Bolin Cai; Geber Peña; Vadim Pisarenko; Gergely Vida; Danielle Doucet; Marlon Lee; Susan Sharpe; Qi Lu; Da-Zhong Xu; Laura Ramos; Edwin A Deitch; Luis Ulloa
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  34     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-22     Completed Date:  2010-11-10     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  205-13     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / therapeutic use*
Blood Coagulation / drug effects
Hemorrhage / drug therapy*
Hyperglycemia / prevention & control
Inflammation / drug therapy*
Intestinal Mucosa / drug effects
Male
NF-kappa B / metabolism
Pyruvates / therapeutic use*
Resuscitation / methods*
Swine
Tumor Necrosis Factor-alpha / blood
Grant Support
ID/Acronym/Agency:
R01 GM084125-01A1/GM/NIGMS NIH HHS; R01 GM084125-02/GM/NIGMS NIH HHS; R01-GM084125/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/NF-kappa B; 0/Pyruvates; 0/Tumor Necrosis Factor-alpha; 617-35-6/ethyl pyruvate
Comments/Corrections

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