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The Failing Heart: Is It an Inefficient Engine or an Engine Out of Fuel?

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

Abstract

To meet its high-energy demand, the heart is very flexible in its choice of energy substrates. It can use a variety of energy substrates which include fatty acids, glucose, lactate, pyruvate, ketones, and amino acids. In the failing heart, significant changes in cardiac energy substrate metabolism occur, although there is no consensus as to exactly what these changes are. Energy starvation in heart failure has been extensively discussed, where reduced oxygen and energy substrate delivery to the heart, reduced cardiac energy substrate uptake, reduced mitochondrial oxidative phosphorylation, and decreased metabolic flexibility have been implicated as contributing factors to the declining mechanical function in heart failure. In addition to energy starvation, there is also the possibility of inefficient energy utilization in the failing heart. This inefficiency can occur at the level of ATP production where the preferential dependence on fatty acids consumes more oxygen per unit ATP and/or the overexpression of uncoupling proteins can increase energy loss as heat rather than ATP production. Increased ATP utilization for non-contractile purposes, such as ionic homeostasis and futile cycling of fatty acids, can also contribute to inefficiency in the failing heart. Impaired phosphocreatine/creatine kinase shuttle activity may also contribute to inefficient transport of ATP from the mitochondria to the contractile myofibrils. The degree and type of energy inefficiency in the failing heart are likely dependent on the pathogenesis and severity of heart failure. In this chapter, we review the various contributors to energy inefficiency in heart failure and discuss the potential to optimize cardiac energy metabolism as a potential treatment for heart failure.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Waleed G. T. Masoud, Alexander S. Clanachan & Gary D. Lopaschuk

  2. Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Gary D. Lopaschuk

  3. Mazankowski Alberta Heart Institute, Edmonton, AB, Canada

    Gary D. Lopaschuk

  4. 423 Heritage Medical Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Gary D. Lopaschuk

Authors
  1. Waleed G. T. Masoud
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  2. Alexander S. Clanachan
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  3. Gary D. Lopaschuk
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Corresponding author

Correspondence to Gary D. Lopaschuk .

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Editors and Affiliations

  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Masoud, W.G.T., Clanachan, A.S., Lopaschuk, G.D. (2013). The Failing Heart: Is It an Inefficient Engine or an Engine Out of Fuel?. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_4

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