title: Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.
abstract: 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: Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors: WeiHong
authors: W
authors: Dong
authors: Bolin
authors: B
authors: Cai
authors: Geber
authors: G
authors: Peña
authors: Vadim
authors: V
authors: Pisarenko
authors: Gergely
authors: G
authors: Vida
authors: Danielle
authors: D
authors: Doucet
authors: Marlon
authors: M
authors: Lee
authors: Susan
authors: S
authors: Sharpe
authors: Qi
authors: Q
authors: Lu
authors: Da-Zhong
authors: DZ
authors: Xu
authors: Laura
authors: L
authors: Ramos
authors: Edwin A
authors: EA
authors: Deitch
authors: Luis
authors: L
authors: Ulloa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D006470:Hemorrhage / Q000188:drug therapy*; D006943:Hyperglycemia / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011773:Pyruvates / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate