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June 15, 2004AJP Heart and Circulatory Physiology

Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation

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Why the study?

Does moderate coronary microembolization-induced heart failure alter myocardial substrate metabolism compared to normal controls in a canine model?

Population

Normal dogs and dogs with microembolization-induced moderate heart failure

Comparison

Microembolization-induced moderate heart failure… vs Normal dogs (healthy controls)

Design

Preclinical

Authors

MCMargaret P. ChandlerCase Western Reserve UniversityJKJános KernerPoznan University of Medical SciencesHHHazel HuangUniversity of Washington

Discussion

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Implication

Suggests metabolic switch occurs late in HF; leaves open timing of malonyl-CoA effects in compensated models.

Key Points

  • To investigate whether moderate, well-compensated heart failure causes a shift from myocardial fatty acid oxidation to glucose oxidation.
  • Assessed cardiac substrate uptake and oxidation in anesthetized open-chest normal dogs (n = 8) and dogs with microembolization-induced heart failure (n = 18, ejection fraction = 28%) using infusions of three isotopic tracers ([9,10-3H]oleate, [U-14C]glucose, and [1-13C]lactate).
  • Measured total activity of pyruvate dehydrogenase, carnitine palmitoyl transferase I (CPT-I) activity and sensitivity to malonyl-CoA, and the kinetics of malonyl-CoA decarboxylase.
  • Myocardial substrate metabolism and the total activity of pyruvate dehydrogenase did not differ between normal controls and dogs with moderate heart failure.
  • CPT-I activity, its sensitivity to malonyl-CoA inhibition, and the kinetics of malonyl-CoA decarboxylase remained unchanged between groups.
  • Myocardial malonyl-CoA content was decreased by 22% in the heart failure group, suggesting less in vivo inhibition of CPT-I activity.

Structured PICO

Does moderate coronary microembolization-induced heart failure alter myocardial substrate metabolism compared to normal controls in a canine model?

P
Population
Normal dogs (n = 8) and dogs with microembolization-induced moderate heart failure (n = 18, ejection fraction = 28%)
I
Intervention
Microembolization-induced moderate heart failure model
C
Comparator
Normal dogs (healthy controls)
O
Outcome
Cardiac substrate uptake and oxidation measured by infusing three isotopic tracers ([9,10-(3)H]oleate, [U-(14)C]glucose, and [1-(13)C]lactate) in anesthetized open-chest animalssurrogate

In a canine model, moderate compensated heart failure does not downregulate myocardial fatty acid oxidation, suggesting the metabolic switch to carbohydrate oxidation is a late-stage phenomenon.

Cite This Study

Chandler et al. (2004) studied this question.

synapsesocial.com/papers/6a75b6b41eaff9cba916141ehttps://doi.org/10.1152/ajpheart.00281.2004

Topics

Heart failureHFrEF treatment
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia2002 · 35 citations
  2. 2Partitioning of pyruvate between oxidation and anaplerosis in swine hearts2000 · 100 citations
  3. 3Effects of moderate hypertension on cardiac function and metabolism in the rabbit.1988 · 240 citations
  4. 4High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5’-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase1995 · 577 citations
  5. 5Probing the Origin of Acetyl-CoA and Oxaloacetate Entering the Citric Acid Cycle from the 13C Labeling of Citrate Released by Perfused Rat Hearts1997 · 61 citations