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Post-Ischemic Treatment with Dipyruvyl-Acetyl-Glycerol Decreases Myocardial Infarct Size in the Pig

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Abstract

The beneficial effects of pyruvate in organ reperfusion injury have been documented, however the therapeutic use of pyruvate has been hindered by the lack of an appropriate delivery method. Pyruvic acid is unstable and high rates of sodium pyruvate infusion are toxic. Dipyruvyl-acetyl-glycerol (DPAG) ester was developed as a novel method for intravenous pyruvate delivery at a high rate without sodium overload. We tested the ability of DPAG to reduce myocardial infarct size when administered after severe myocardial ischemia in an anesthetized open-chest pig model of ischemia-reperfusion injury. Ischemia was induced by total occlusion of the distal 2/3 of the left anterior descending coronary artery for one hour, followed by two hours of reperfusion. Animals were either untreated (n = 7), or treated with intravenous DPAG (8.0 mg/kg−1 · min−1, n = 8) during the two hours of reperfusion. Infarct size was measured on blinded samples using tetrazolium staining. The DPAG treated group had elevated pyruvate levels (0.82 ± 0.07 mM) and reduced infarct size (20.1 ± 4.2% of the volume at risk, compared to 30.8 ± 4.6% in the untreated animals (p < 0.05)), with no difference in blood pressure or heart rate between groups. In conclusion, an intravenous infusion of DPAG safely increases arterial pyruvate concentration and reduces myocardial infarct size following myocardial ischemia.

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Authors and Affiliations

  1. Departments of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA

    William C. Stanley, Krista M. Kivilo & Ashish R. Panchal

  2. Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA

    Peter H. Hallowell, Catherine Bomont & Takhar Kasumov

  3. Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA

    Henri Brunengraber

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  1. William C. Stanley
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  2. Krista M. Kivilo
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  3. Ashish R. Panchal
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  4. Peter H. Hallowell
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  5. Catherine Bomont
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  6. Takhar Kasumov
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  7. Henri Brunengraber
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Stanley, W.C., Kivilo, K.M., Panchal, A.R. et al. Post-Ischemic Treatment with Dipyruvyl-Acetyl-Glycerol Decreases Myocardial Infarct Size in the Pig. Cardiovasc Drugs Ther 17, 209–216 (2003). https://doi.org/10.1023/A:1026163921643

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