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Metabolic Approaches to the Treatment of Ischemic Heart Disease: The Clinicians' Perspective

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Abstract

This review article discusses pharmacological approaches to optimizing myocardial metabolism during ischemia. Fatty acids are the main fuel for the healthy heart, with a lesser contribution coming from the oxidation of glucose and lactate. Myocardial ischaemia dramatically alters fuel metabolism, causing an accelerated rate of glucose conversion to lactate and a switch from lactate uptake by the heart to lactate production. This causes a dramatic disruption in cell homeostasis (e.g. lactate accumulation and a decrease in pH and ATP). Paradoxically, moderately ischemic tissue (∼50% of normal flow) continues to derive most of its energy (50–70%) from the oxidation of fatty acids despite a high rate of lactate production. This ischaemia-induced disruption in cardiac metabolism can be minimized by metabolic agents that reduce fatty acid oxidation and increase the combustion of glucose and lactate, resulting in clinical benefit to the ischemic patient. Agents that inhibit fatty acid beta-oxidation, such as ranolazine and trimetazidine, have proven to be effective in the treatment of stable angina. Treatment of acute myocardial infarction patients with an infusion of the glucose-insulin-potassium, which results in suppression of myocardial fatty acid oxidation and greater glucose combustion, has proven effective in reducing mortality. These metabolic therapies are free of direct hemodynamic or chronotropic effects, and thus are well positioned for use alongside traditional agents such as beta-adrenergic receptor antagonists or calcium channel antagonists.

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Authors and Affiliations

  1. CV Therapeutics, Palo Alto, California

    Andrew A. Wolff

  2. Division of Cardiology, Department of Medicine and Veterans' Affairs Medical Center, University of California, San Francisco, California, USA

    Andrew A. Wolff

  3. Cato Research Israel and Department of Medicine C, Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv, Israel

    Heschi H. Rotmensch

  4. Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, USA

    William C. Stanley

  5. Division of Cardiology, University of Ferrara, and Center of Cardiovascular Pathophysiology, Fondazione Clinica del Lavoro “S. Maugeri”, Gussago, Brescia, Italy

    Roberto Ferrari

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  1. Andrew A. Wolff
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  4. Roberto Ferrari
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Wolff, A.A., Rotmensch, H.H., Stanley, W.C. et al. Metabolic Approaches to the Treatment of Ischemic Heart Disease: The Clinicians' Perspective. Heart Fail Rev 7, 187–203 (2002). https://doi.org/10.1023/A:1015384710373

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