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Biophysics of the Failing Heart pp 91–121Cite as

Biophysical Mechanisms for the Metabolic Component of Impaired Heart Function

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Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

This chapter explores metabolic basis of cardiac decompensation through maladaptative changes in metabolic enzyme expression that leads to dysregulation of lipid and carbohydrate metabolism. The consequences of this metabolic dysregulation are examined in detail with respect to inefficiencies in energy production in the myocardium that contribute to the energy starved heart and dysregulation of lipid metabolism that contributes to the potential for lipotoxicity. The initial section considers the link between early metabolic changes and early manifestations of impaired contractility in the decompensating, myopathic heart. Changes in the metabolic fate of the primary fuel for ATP in the heart, long chain fatty acids, occur in the decompensated and failing heart at the level of gene expression. As discussed below, long chain fatty acid oxidation and storage are both impaired in failing hearts, leading to a general dysregulation of lipid dynamics in the cardiomyocyte that contributes to the energy starved condition of the heart. The consequential metabolic adaptations in the cardiomyocyte invoke changes in the cytosolic and mitochondrial metabolism of not only lipids but also carbohydrates, as glucose is inefficiently metabolized for the production ATP. With changes in glycolytic activity and the reduction/oxidation state in the cytosolic space, transport of metabolic intermediates across the mitochondrial membrane serves to transduce the pathophysiological state of the cytosol to the mitochondrial matrix, while reciprocal exchange of intermediates from oxidative pathways links mitochondrial activity to the reduction/oxidation state of the cytosol. The latter sections of this chapter examine the details of altered mitochondrial transporter activity in response to the bioenergetic and biophysical state of the cell.

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Authors and Affiliations

  1. Departments of Physiology and Biophysics, Medicine, and Bioengineering, University of Illinois at Chicago College of Medicine, MC-901, 835 South Wolcott Avenue, Chicago, IL, 60612, USA

    E. Douglas Lewandowski Ph.D.

  2. UIC Center for Cardiovascular Research, 909 S. Wolcott Ave., M/C 801, Chicago, IL, 60612, USA

    E. Douglas Lewandowski Ph.D.

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  1. Dept. of Physiology & Biophysics, University of Illinois at Chicago, Chicago, USA

    R. John Solaro

  2. University of Arizona, Tucson, Arizona, USA

    Jil C. Tardiff

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Lewandowski, E.D. (2013). Biophysical Mechanisms for the Metabolic Component of Impaired Heart Function. In: Solaro, R., Tardiff, J. (eds) Biophysics of the Failing Heart. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7678-8_5

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