Postischemic treatment with ethyl pyruvate prevents adenosine triphosphate depletion, ameliorates inflammation, and decreases thrombosis in a murine model of hind-limb ischemia and reperfusion

J Trauma. 2011 Jan;70(1):103-10; discussion 110. doi: 10.1097/TA.0b013e3182031ccb.


Introduction: Experiments were designed to investigate the effects of ethyl pyruvate (EP) in a murine model of hind-limb ischemia-reperfusion (IR) injury.

Methods: C57BL6 mice underwent 90 minutes of unilateral ischemia followed by 24 hours of reperfusion using two treatment protocols. For the preischemic treatment (pre-I) protocol, mice (n=6) were given 300 mg/kg EP before ischemia, followed by 150 mg/kg of EP just before reperfusion and at 6 hours and 12 hours after reperfusion. In a postischemic treatment (post-I) protocol, mice (n=7) were treated with 300 mg/kg EP at the end of the ischemic period, then 15 minutes later, and 2 hours after reperfusion and 150 mg/kg of EP at 4 hours, 6 hours, 10 hours, 16 hours, and 22 hours after reperfusion. Controls mice for both protocols were treated with lactated Ringers alone at time intervals identical to EP. Skeletal muscle levels of adenosine triphosphate (ATP), interleukin-1β, keratinocyte chemoattractant protein, and thrombin antithrombin-3 complex were measured. Skeletal muscle architectural integrity was assessed microscopically.

Results: ATP levels were higher in mice treated with EP compared with controls under the both treatment protocols (p=0.02). Interleukin-1β, keratinocyte chemoattractant protein, thrombin antithrombin-3 complex (p<0.05), and the percentage of injured fibers (p<0.0001) were significantly decreased in treated versus control mice under the both protocols.

Conclusion: Muscle fiber injury and markers of tissue thrombosis and inflammation were reduced, and ATP was preserved with EP in pre-I and post-I protocols. Further investigation of the efficacy of EP to modulate IR injury in a larger animal model of IR injury is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antithrombin III / analysis
  • Disease Models, Animal
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Interleukin-1 / analysis
  • Lactates / analysis
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • Peptide Hydrolases / analysis
  • Peroxidase / analysis
  • Pyruvates / therapeutic use*
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Thrombosis / etiology
  • Thrombosis / prevention & control*


  • Interleukin-1
  • Lactates
  • Pyruvates
  • antithrombin III-protease complex
  • ethyl pyruvate
  • Adenosine Triphosphate
  • Antithrombin III
  • Peroxidase
  • Peptide Hydrolases