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

Robert S. Crawford, Hassan Albadawi, Marvin D. Atkins, John J. Jones, Mark F. Conrad, William G. Austen, Mitchell P. Fink, Michael T. Watkins

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume70
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • Inflammation
  • Ischemia-reperfusion
  • Skeletal muscle
  • cytokines

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Postischemic treatment with ethyl pyruvate prevents adenosine triphosphate depletion, ameliorates inflammation, and decreases thrombosis in a murine model of hind-limb ischemia and reperfusion'. Together they form a unique fingerprint.

  • Cite this