Tickle, PG orcid.org/0000-0003-0389-3580, Hendrickse, PW, Degens, H et al. (1 more author) (2020) Impaired skeletal muscle performance as a consequence of random functional capillary rarefaction can be restored with overload‐dependent angiogenesis. The Journal of Physiology, 598 (6). pp. 1187-1203. ISSN 0022-3751
Abstract
To what extent microvascular rarefaction contributes to impaired skeletal muscle function remains unknown. Our understanding of whether pathological changes in the microcirculation can be reversed remains limited by a lack of basic physiological data in otherwise healthy tissue. Principal objectives were: 1) quantify the effect of random microvascular rarefaction on limb perfusion and muscle performance; 2) determine if these changes could be reversed. We developed a novel protocol in rats whereby microspheres injected into the femoral artery allowed a unilateral reduction in functional capillary density in the extensor digitorum longus (EDL), and assessed acute and chronic effects on muscle function. Simultaneous bilateral EDL force and hindlimb blood flow measurements were made during electrical stimulation. Following functional capillary rarefaction there was an acute microsphere dose‐dependent reduction in muscle fatigue resistance (P < 0.001), despite preserved femoral artery perfusion. Histological analysis of EDL samples taken from injected animals confirmed a positive correlation between the proportion of functional capillaries and fatigue resistance (P = 0.002). Such impaired performance persisted for at least 2 weeks (P = 0.016). Concomitant mechanical overload improved both perfused capillary density and fatigue resistance (P < 0.05), confirming that the capacity for muscle remodelling was retained following chronic distributed ischaemia, and that the impact of capillary rarefaction could be alleviated. These results demonstrate that loss of functional capillaries is detrimental to muscle function, even in otherwise healthy tissue, independent of arterial perfusion. Restoration of muscle performance following a mechanical overload stimulus indicates that angiogenic treatments to alleviate microvascular rarefaction may be key to restoring exercise tolerance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 University of Leeds. 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 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | blood flow; fatigue; ischaemia; microcirculation; microspheres; 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: | 13 Feb 2020 16:27 |
Last Modified: | 25 Jun 2023 22:09 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1113/jp278975 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:156995 |