Knuiman, P, Straw, S orcid.org/0000-0002-2942-4574, Gierula, J orcid.org/0000-0001-9588-191X et al. (5 more authors) (2021) Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure. ESC Heart Failure, 8 (2). pp. 898-907. ISSN 2055-5822
Abstract
Aims:
Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole‐body measures of exercise limitation in HFrEF.
Methods and results:
Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp‐incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O2peak), lactate threshold (V̇O2LT), the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2LT), peak circulatory power (CircPpeak), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O2peak (r = 0.40–0.64; P < 0.05), V̇O2LT (r = 0.52–0.72; P < 0.05), and CircPpeak (r = 0.42–0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O2peak and 80% of the variability in V̇O2LT, respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model.
Conclusions:
Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non‐invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O2peak, V̇O2LT, and CircPpeak. When combined with baseline patient characteristics, over 50% of the variability in V̇O2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Exercise; HFrEF; Lactate threshold; Skeletal muscle; V̇O2peak |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Clinical & Population Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/S025472/1 Heart Research UK RG2683/19/21 |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Mar 2021 15:50 |
Last Modified: | 13 Jun 2022 13:35 |
Status: | Published |
Publisher: | Wiley Open Access |
Identification Number: | 10.1002/ehf2.13272 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171876 |