Espino‐Gonzalez, E, Tickle, PG orcid.org/0000-0003-0389-3580, Benson, AP orcid.org/0000-0003-4679-9842 et al. (4 more authors) (2021) Abnormal skeletal muscle blood flow, contractile mechanics and fibre morphology in a rat model of obese‐HFpEF. The Journal of Physiology, 599 (3). pp. 981-1001. ISSN 0022-3751
Abstract
Peripheral skeletal muscle and vascular alterations induced by heart failure with preserved ejection fraction (HFpEF) remain poorly identified, with limited therapeutic targets. This study used a cardiometabolic obese‐HFpEF rat model to comprehensively phenotype skeletal muscle mechanics, blood flow, microvasculature and fibre atrophy. Lean (n = 8) and obese‐HFpEF (n = 8) ZSF1 rats were compared. Skeletal muscles (soleus and diaphragm) were assessed for in vitro contractility (isometric and isotonic properties) alongside indices of fibre‐type cross‐sectional area, myosin isoform, and capillarity, and estimated muscle PO2. In situ extensor digitorum longus (EDL) contractility and femoral blood flow were assessed. HFpEF soleus demonstrated lower absolute maximal force by 22%, fibre atrophy by 24%, a fibre‐type shift from I to IIa, and a 17% lower capillary‐to‐fibre ratio despite increased capillary density (all P < 0.05) with preserved muscle PO2 (P = 0.115) and isometric specific force (P > 0.05). Soleus isotonic properties (shortening velocity and power) were impaired by up to 17 and 22%, respectively (P < 0.05), while the magnitude of the exercise hyperaemia was attenuated by 73% (P = 0.012) in line with higher muscle fatigue by 26% (P = 0.079). Diaphragm alterations (P < 0.05) included Type IIx fibre atrophy despite Type I/IIa fibre hypertrophy, with increased indices of capillarity alongside preserved contractile properties during isometric, isotonic, and cyclical contractions. In conclusion, obese‐HFpEF rats demonstrated blunted skeletal muscle blood flow during contractions in parallel to microvascular structural remodelling, fibre atrophy, and isotonic contractile dysfunction in the locomotor muscles. In contrast, diaphragm phenotype remained well preserved. This study identifies numerous muscle‐specific impairments that could exacerbate exercise intolerance in obese‐HFpEF.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | blood flow; diaphragm; heart failure; HFpEF; muscle atrophy; muscle contraction; skeletal muscle |
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) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Jan 2021 15:38 |
Last Modified: | 05 Jan 2023 16:54 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1113/jp280899 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169897 |