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Updated: Jun 23, 2026
12:24
Methods for the Determination of Rates of Glucose and Fatty Acid Oxidation in the Isolated Working Rat Heart
Published on: September 28, 2016
Metabolic mechanisms in heart failure
Houman Ashrafian1, Michael P Frenneaux, Lionel H Opie
1Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. houman.ashrafian@cardiov.ox.ac.uk
Circulation
|July 25, 2007
Summary
Heart failure can worsen metabolism and insulin resistance, creating a harmful cycle. New therapies targeting these metabolic changes may improve heart function and reduce mortality.
Area of Science:
- Cardiology
- Metabolic Medicine
- Biochemistry
Background:
- Neurohumoral antagonism has improved heart failure outcomes but residual mortality remains high.
- Heart failure is linked to metabolic abnormalities, including insulin resistance, potentially driven by neurohumoral activation.
- A detrimental cycle of heart failure promoting metabolic changes, which in turn worsen heart failure, is hypothesized.
Purpose of the Study:
- To review the cellular mechanisms and pathophysiology of altered metabolism and insulin resistance in heart failure.
- To explore how these metabolic changes contribute to the progression of heart failure.
- To discuss current and novel therapeutic strategies targeting metabolic dysfunction in heart failure.
Main Methods:
- Review of existing literature on myocardial metabolism, insulin resistance, and heart failure pathophysiology.
- Analysis of cellular mechanisms linking neurohumoral activation to metabolic perturbations.
- Discussion of therapeutic interventions aimed at mitigating aberrant metabolism.
Main Results:
- Heart failure can induce insulin resistance and alter myocardial substrate utilization, favoring free fatty acid over glucose metabolism.
- These metabolic changes lead to reduced myocardial energy (ATP, phosphocreatine) and impaired mechanical efficiency.
- Neurohumoral activation, adverse fatty acid metabolism, and insulin resistance are key contributors to myocardial energetic deficits.
Conclusions:
- Altered myocardial metabolism and insulin resistance represent a critical, self-perpetuating aspect of heart failure progression.
- Therapies including neurohumoral antagonism, lifestyle modifications, and novel metabolic modulators show promise.
- Targeting metabolic pathways offers a potential strategy to further reduce mortality and improve cardiac function in heart failure patients.
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