Warren, PM, Kissane, RWP, Egginton, S orcid.org/0000-0002-3084-9692 et al. (2 more authors) (2021) Oxygen transport kinetics underpin rapid and robust diaphragm recovery following chronic spinal cord injury. The Journal of Physiology, 599 (4). pp. 1199-1224. ISSN 0022-3751
Abstract
Months after spinal cord injury (SCI), respiratory deficits remain the primary cause of morbidity and mortality for patients. It is possible to induce partial respiratory motor functional recovery in chronic SCI following 2 weeks of spinal neuroplasticity. However, the peripheral mechanisms underpinning this recovery are largely unknown, limiting development of new clinical treatments with potential for complete functional restoration. Utilizing a rat hemisection model, diaphragm function and paralysis was assessed and recovered at chronic time points following trauma through chondroitinase ABC induced neuroplasticity. We simulated the diaphragm's in vivo cyclical length change and activity patterns using the work loop technique at the same time as assessing global and local measures of the muscles histology to quantify changes in muscle phenotype, microvascular composition, and oxidative capacity following injury and recovery. These data were fed into a physiologically informed model of tissue oxygen transport. We demonstrate that hemidiaphragm paralysis causes muscle fibre hypertrophy, maintaining global oxygen supply, although it alters isolated muscle kinetics, limiting respiratory function. Treatment induced recovery of respiratory activity normalized these effects, increasing oxygen supply, restoring optimal diaphragm functional properties. However, metabolic demands of the diaphragm were significantly reduced following both injury and recovery, potentially limiting restoration of normal muscle performance. The mechanism of rapid respiratory muscle recovery following spinal trauma occurs through oxygen transport, metabolic demand and functional dynamics of striated muscle. Overall, these data support a systems‐wide approach to the treatment of SCI, and identify new targets to mediate complete respiratory recovery.
Metadata
Item Type: | Article |
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Authors/Creators: |
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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: | angiogenesis; capillary domain area; diaphragm; mechanical properties; spinal cord injury |
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) |
Funding Information: | Funder Grant number Wings For Life Spinal Cord Research Foundation WFL-UK-008/15 MRC (Medical Research Council) MR/S011110/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Oct 2020 15:17 |
Last Modified: | 05 Jan 2023 16:48 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1113/JP280684 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167390 |