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Departments of 1 Critical Care Medicine, 2 Surgery, and 4 Pathology, and 3 Center for Biologic Imaging, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261
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 [Ringer ethyl pyruvate solution (REPS)] and evaluated in a murine model of hemorrhagic shock
and resuscitation (HS/R). Resuscitation with REPS instead of Ringer
lactate solution (RLS) significantly improved survival at 24 h and
abrogated 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 nuclear
factor-
B in liver and colonic mucosa after HS/R and also decreased
the expression of inducible nitric oxide synthase, tumor necrosis
factor, cyclooxygenase-2, and interleukin-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.
translocation; bacterial; permeability; mucosal; tumor necrosis factor; cyclooxygenase-2; inducible nitric oxide synthase
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