Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults

Knee osteoarthritis (OA) is the leading cause of physical disability in older adults. Total knee arthroplasty (TKA) is a common treatment for advanced stage knee OA that alleviates knee pain, but it is associated with precipitous reductions in physical function early after surgery that can take mont...

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Main Authors: Michael J. Toth, Patrick D. Savage, Deena B. Snoke, Emma R. Bellefleur, Michael DeSarno, Timothy W. Tourville, Michael Blankstein, Alexander R. Keeble, Sara Gonzalez-Velez, Christopher S. Fry, Jennifer Stevens-Lapsley, Nathaniel J. Nelms
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Experimental Gerontology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0531556525001603
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author Michael J. Toth
Patrick D. Savage
Deena B. Snoke
Emma R. Bellefleur
Michael DeSarno
Timothy W. Tourville
Michael Blankstein
Alexander R. Keeble
Sara Gonzalez-Velez
Christopher S. Fry
Jennifer Stevens-Lapsley
Nathaniel J. Nelms
author_facet Michael J. Toth
Patrick D. Savage
Deena B. Snoke
Emma R. Bellefleur
Michael DeSarno
Timothy W. Tourville
Michael Blankstein
Alexander R. Keeble
Sara Gonzalez-Velez
Christopher S. Fry
Jennifer Stevens-Lapsley
Nathaniel J. Nelms
author_sort Michael J. Toth
collection DOAJ
description Knee osteoarthritis (OA) is the leading cause of physical disability in older adults. Total knee arthroplasty (TKA) is a common treatment for advanced stage knee OA that alleviates knee pain, but it is associated with precipitous reductions in physical function early after surgery that can take months or years to recover. Sustaining neuromuscular activation after surgery with neuromuscular electrical stimulation (NMES) can improve recovery of physical function, but the mechanisms underlying its benefits are unclear. To examine the unique effects of NMES on skeletal muscle, we randomized older adult patients (70 % female) to early NMES (n = 11) or no intervention (n = 12) for 5 weeks after surgery. We measured skeletal muscle (vastus lateralis) fiber size, contractility, mitochondrial content, and mRNA abundance pre-surgery and 5 weeks post-surgery. NMES diminished TKA-induced muscle fiber atrophy in fast-twitch, myosin heavy chain (MHC) IIA fibers and improved or preserved single muscle fiber contractility in MHC I and MHC IIA fibers, respectively. In MHC IIA fibers, the beneficial effects of NMES to sustain fiber force production were explained at the molecular level by preservation of strongly bound, myosin-actin crossbridges. Additionally, TKA-induced increases in markers of denervation (CHRNA1 and MYOG) in controls were prevented by NMES. Our results identify beneficial effects of sustaining neuromuscular activation early, post-TKA with NMES on skeletal muscle fiber size and function and potential molecular mechanisms underlying these effects.
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spelling doaj-art-8465ee2e16354c2aaf8d4e74c8bc151c2025-08-20T03:12:49ZengElsevierExperimental Gerontology1873-68152025-10-0120911283110.1016/j.exger.2025.112831Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adultsMichael J. Toth0Patrick D. Savage1Deena B. Snoke2Emma R. Bellefleur3Michael DeSarno4Timothy W. Tourville5Michael Blankstein6Alexander R. Keeble7Sara Gonzalez-Velez8Christopher S. Fry9Jennifer Stevens-Lapsley10Nathaniel J. Nelms11Department of Medicine, University of Vermont College of Medicine, Burlington, VT, United States of America; Department of Orthopaedics and Rehabilitation, University of Vermont College of Medicine, Burlington, VT, United States of America; Corresponding author at: University of Vermont College of Medicine, Firestone Biomedical Research Building Room 260, 149 Beaumont Ave, Burlington, VT 05405, United States of America.Department of Medicine, University of Vermont College of Medicine, Burlington, VT, United States of AmericaDepartment of Medicine, University of Vermont College of Medicine, Burlington, VT, United States of AmericaDepartment of Medicine, University of Vermont College of Medicine, Burlington, VT, United States of AmericaDepartment of the Biomedical Statistics Core, University of Vermont College of Medicine, United States of AmericaDepartment of Orthopaedics and Rehabilitation, University of Vermont College of Medicine, Burlington, VT, United States of America; Department of Rehabilitation and Movement Science, College of Nursing and Health Science, University of Vermont, Burlington, VT, United States of AmericaDepartment of Orthopaedics and Rehabilitation, University of Vermont College of Medicine, Burlington, VT, United States of AmericaDepartment of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, United States of AmericaDepartment of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, United States of AmericaDepartment of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, United States of AmericaDepartment of Physical Medicine and Rehabilitation, College of Medicine, University of Colorado Anschutz Medical Campus, United States of America; VA Eastern Colorado Geriatric Research Education and Clinical Center, Denver, CO, United States of AmericaDepartment of Orthopaedics and Rehabilitation, University of Vermont College of Medicine, Burlington, VT, United States of AmericaKnee osteoarthritis (OA) is the leading cause of physical disability in older adults. Total knee arthroplasty (TKA) is a common treatment for advanced stage knee OA that alleviates knee pain, but it is associated with precipitous reductions in physical function early after surgery that can take months or years to recover. Sustaining neuromuscular activation after surgery with neuromuscular electrical stimulation (NMES) can improve recovery of physical function, but the mechanisms underlying its benefits are unclear. To examine the unique effects of NMES on skeletal muscle, we randomized older adult patients (70 % female) to early NMES (n = 11) or no intervention (n = 12) for 5 weeks after surgery. We measured skeletal muscle (vastus lateralis) fiber size, contractility, mitochondrial content, and mRNA abundance pre-surgery and 5 weeks post-surgery. NMES diminished TKA-induced muscle fiber atrophy in fast-twitch, myosin heavy chain (MHC) IIA fibers and improved or preserved single muscle fiber contractility in MHC I and MHC IIA fibers, respectively. In MHC IIA fibers, the beneficial effects of NMES to sustain fiber force production were explained at the molecular level by preservation of strongly bound, myosin-actin crossbridges. Additionally, TKA-induced increases in markers of denervation (CHRNA1 and MYOG) in controls were prevented by NMES. Our results identify beneficial effects of sustaining neuromuscular activation early, post-TKA with NMES on skeletal muscle fiber size and function and potential molecular mechanisms underlying these effects.http://www.sciencedirect.com/science/article/pii/S0531556525001603DisablementMyosinDenervationRehabilitation
spellingShingle Michael J. Toth
Patrick D. Savage
Deena B. Snoke
Emma R. Bellefleur
Michael DeSarno
Timothy W. Tourville
Michael Blankstein
Alexander R. Keeble
Sara Gonzalez-Velez
Christopher S. Fry
Jennifer Stevens-Lapsley
Nathaniel J. Nelms
Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
Experimental Gerontology
Disablement
Myosin
Denervation
Rehabilitation
title Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
title_full Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
title_fullStr Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
title_full_unstemmed Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
title_short Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults
title_sort sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size contractility and innervation in older adults
topic Disablement
Myosin
Denervation
Rehabilitation
url http://www.sciencedirect.com/science/article/pii/S0531556525001603
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