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Articles in PresS, published online ahead of print February 27, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00022.2002
Submitted on January 16, 2002
Accepted on February 21, 2002
1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
5 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: finkmp{at}anes.upmc.edu.
Administration of pyruvate, an effective scavenger of reactive oxygen species, has been shown to be salutary in numerous models of redox-mediated tissue or organ injury. Pyruvate, however, is unstable in solution, and, hence, is not attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which is thought to be more stable than the parent compound, was formulated in a calcium-containing balanced salt solution (REPS), and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R). Resuscitation with REPS instead of Ringer's lactate solution (RLS) significantly improved survival at 24 h, and abrograted bacterial translocation to mesenteric lymph nodes and the development of increased ileal mucosal permeability to FITC-labeled dextran (4,000 Da) at 4 h. Mice treated with REPS instead of RLS also had lower circulating levels of alanine aminotransferase at 4 h. Treatment with REPS instead of RLS decreased activation of NF-
B in liver and colonic mucosa following HS/R, and also decreased the expression of inducible nitric oxide synthase, TNF, cyclooxygenase-2, and IL-6 mRNA in liver, ileal mucosa and/or colonic mucosa. These data support the view that resuscitation with REPS modulates the inflammatory response and decreases hepatocellular and gut mucosal injury in mice subjected to HS/R.
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