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.
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Authors | Robert S Crawford, Hassan Albadawi, Marvin D Atkins, John J Jones, Mark F Conrad, William G Austen Jr, Mitchell P Fink, Michael T Watkins |
Journal | The Journal of trauma
(J Trauma)
Vol. 70
Issue 1
Pg. 103-10; discussion 110
(Jan 2011)
ISSN: 1529-8809 [Electronic] United States |
PMID | 21217488
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-1
- Lactates
- Pyruvates
- antithrombin III-protease complex
- ethyl pyruvate
- Adenosine Triphosphate
- Antithrombin III
- Peroxidase
- Peptide Hydrolases
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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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