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

AbstractINTRODUCTION:
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.
AuthorsRobert S Crawford, Hassan Albadawi, Marvin D Atkins, John J Jones, Mark F Conrad, William G Austen Jr, Mitchell P Fink, Michael T Watkins
JournalThe Journal of trauma (J Trauma) Vol. 70 Issue 1 Pg. 103-10; discussion 110 (Jan 2011) ISSN: 1529-8809 [Electronic] United States
PMID21217488 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-1
  • Lactates
  • Pyruvates
  • antithrombin III-protease complex
  • ethyl pyruvate
  • Adenosine Triphosphate
  • Antithrombin III
  • Peroxidase
  • Peptide Hydrolases
Topics
  • Adenosine Triphosphate (analysis, metabolism)
  • Animals
  • Antithrombin III (analysis)
  • Disease Models, Animal
  • Inflammation (drug therapy, etiology)
  • Interleukin-1 (analysis)
  • Lactates (analysis)
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal (chemistry, drug effects, pathology)
  • Peptide Hydrolases (analysis)
  • Peroxidase (analysis)
  • Pyruvates (therapeutic use)
  • Reperfusion Injury (complications, drug therapy, metabolism, pathology, physiopathology)
  • Thrombosis (etiology, prevention & control)

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