title: Resuscitation with Ringer's ethyl pyruvate solution prolongs survival and modulates plasma cytokine and nitrite/nitrate concentrations in a rat model of lipopolysaccharide-induced shock.
abstract: The glycolytic intermediate, pyruvate, is capable of scavenging reactive oxygen species (ROS). However, this compound is relatively unstable and hence is not useful as a therapeutic agent. Ethyl pyruvate, a simple derivative of pyruvate, appears to be more stable, and when formulated in a calcium-containing Ringer's-type balanced salt solution (REPS), has been shown to be salutary in rat models of two pathophysiological conditions--mesenteric ischemia/reperfusion and hemorrhagic shock/resuscitation--that are thought to be mediated, at least in part, by ROS. Because ROS also have been implicated in the pathogenesis of lipopolysaccharide (LPS)-induced shock, we carried out a series of experiments to determine if REPS is beneficial in this condition. Anesthetized rats were challenged with intravenous LPS (20 mg/kg). When mean arterial pressure (MAP) decreased to 60 mmHg, 3- to 5-mL boluses of either REPS (n = 10) or Ringer's lactate solution (RLS; n = 10) were infused as needed to prevent MAP from decreasing further. By design, the maximal volume of fluid infused was 7 mL/kg. Resuscitation with REPS as compared with RLS prolonged survival time (498 +/- 48 min vs. 362 +/- 30 min; P = 0.0014). Resuscitation with REPS as compared with RLS also was associated with significantly lower circulating concentrations of nitrite/nitrate and interleukin (IL)-6 and higher plasma levels of IL-10. These data support the view that delayed treatment with REPS modulates the inflammatory response to LPS, and prolongs survival time in a lethal model of endotoxic shock.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Venkataraman
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Mingchen
authors.initials: M
authors.lastname: Song
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D007552:Isotonic Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012769:Shock / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D007552:Isotonic Solutions; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; C439503:Ringer's ethyl pyruvate; D019344:Lactic Acid