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

Shock. 2002 Dec;18(6):507-12. doi: 10.1097/00024382-200212000-00004.


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.

MeSH terms

  • Animals
  • Cytokines / blood*
  • Disease Models, Animal*
  • Isotonic Solutions / pharmacology
  • Isotonic Solutions / therapeutic use*
  • Lactic Acid / blood
  • Lipopolysaccharides / pharmacology*
  • Male
  • Nitrates / blood
  • Nitrites / blood
  • Rats
  • Rats, Sprague-Dawley
  • Resuscitation / methods*
  • Shock / blood*
  • Shock / chemically induced
  • Shock / drug therapy*
  • Shock / immunology
  • Survival Analysis


  • Cytokines
  • Isotonic Solutions
  • Lipopolysaccharides
  • Nitrates
  • Nitrites
  • Ringer's ethyl pyruvate
  • Lactic Acid