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Congestive Heart Failure as Metabolic Disease

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Frontiers in Cardiovascular Health

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 9))

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Summary

The aim of the present paper is to recall some of our previous data which bring an evidence that hearts of rats with 3-mo-old aorto-caval fistula are metabolically restricted. Due to a 40 per cent depletion of tissue L-carnitine, related to impaired carrier-mediated carnitine transport, they are unable to utilize correctly both carbohydrates and long-chain fatty acids during in vitro per fusicus. This results in substrate limitation of their oxidative phosphorylation reflected by decreased VO2max. At the same time, when supplied with 10mM glucose, insulin and 1.2 mM palmitate, volume-overloaded hearts seem to operate at significantly higher ΔG’ATP at each workload studied. The limitation of oxidative phosphorylation disappears when octanoate instead of palmitate is used for the in vitro perfusions. This short-chain fatty acid bypasses mitochondrial carnitine acyltransferases and, thus, improves mitochondrial NADH availability. This, per se, improves the kinetics of oxidative phosphorylation and left ventricular performance of volume-overloaded hearts. The long-term administration of propionyl-L-carnitine which restores tissue levels of L-carnitine has similar effects. In this latter case, we observe an acceleration of palmitate oxidation and an improved coupling between glycolysis and glucose oxidation. This recovery of both fatty acid and carbohydrate utilization improves mitochondrial NADH availability and, thus, increases VO2max of volume-overloaded hearts. At the same time, cytololic phosphorylation potential and ADPf become regulatory again. The restitution of energy transfer from metabolic substrates to cytosolic adenine nucleotides is thus associated with an acceleration of ATP turnover and with a significant improvement of left ventricular function. Our data suggest that the pathogenesis of congestive heart failure may involve a metabolic component, i.e. the simultaneous inhibition of long-chain fatty acid and glucose oxidation, which results in the kinetic failure of oxidative phosphorylation. It follows that appropriate pharmacological interventions that improve mitochondrial NADH availability and, thus, the kinetics of oxidative phosphorylation may be used to delay the transition from cardiac hypertrophy to congestive heart failure. Prospective molecular mechanisms which may explain the recovery of contractile function in substrate-repleted mechanically-overloaded hearts are briefly discussed.

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Authors and Affiliations

  1. Laboratoire d’Energétique et de Cardiologie cellulaire, INSERM, France

    Dr. Josef Moravec

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  1. Dr. Josef Moravec
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Correspondence to Josef Moravec .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), H. Ivan Berkowitz MBA (Consultant) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Consultant) &  (Professor)

  2. Institute of Circulatory & Respiratory Health, Canadian Institutes of Health Research, Vancouver, Canada

    Arun Chockalingam PhD (Assistant Director) (Assistant Director)

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Moravec, J. (2003). Congestive Heart Failure as Metabolic Disease. In: Dhalla, N.S., Chockalingam, A., Berkowitz, H.I., Singal, P.K. (eds) Frontiers in Cardiovascular Health. Progress in Experimental Cardiology, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0455-9_20

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  • DOI: https://doi.org/10.1007/978-1-4615-0455-9_20

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