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Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease

  • Thomas J. Wargovich
    Correspondence
    Address for reprints: Thomas J. Wargovich, MD, Box J-277. Division of Cardiology, Department of Medicine, JHM Health Center, University of Florida, Gainesville, Florida 32610.
    Footnotes
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • Robert G. MacDonald
    Footnotes
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • James A. Hill
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • Robert L. Feldman
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • Peter W. Stacpoole
    Footnotes
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • Carl J. Pepine
    Affiliations
    From the Division of Cardiology and Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Florida, USA

    From the Veterans Administration Medical Center, Gainesville, Florida, USA
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  • Author Footnotes
    1 Dr. Wargovich was supported by a grant from the Florida Chapter of the American Heart Association.
    2 Dr. Macdonald was supported in part by a grant from the Canadian Heart Foundation; presently at Maritime Heart Center, Dalhousie University, Victoria General Hospital, Halifax, Nova Scotia, Canada.
    3 Dr. Stacpoole is the recipient of a Research Career Development Award from the National Institutes of Health, Bethesda, Maryland.
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      Abstract

      Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 ± 7 to 87 ± 7 ml and decreased systemic vascular resistance from 1,573 ± 199 to 1,319 ± 180 dynes · s · cm−5 (both, p < 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p < 0.05). Myocardial lactate consumption was maintained (21 ± 8 vs 19 ± 11 × 103 mEq/min, p is not significant at p < 0.05 level) at a lower arterial lactate concentration (0.72 ± 0.09 to 0.47 ± 0.08 mEq/liter, p < 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease.
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