Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial.

Autor: Stephenson MC; Centre for Translational MR Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Krishna L; Division of Sports Medicine and Surgery, Department of Orthopaedic Surgery, National University Hospital, National University Health System, Singapore., Pannir Selvan RM; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore., Tai YK; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore., Kit Wong CJ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore., Yin JN; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore., Toh SJ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore., Torta F; Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore.; Precision Medicine Translational Research Program, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Triebl A; Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore., Fröhlich J; Fields at Work GmbH, Zurich, Switzerland., Beyer C; Centre Suisse d'électronique et de Microtechnique, CSEM SA, Neuchatel, Switzerland., Li JZ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Tan SS; Division of Sports Medicine and Surgery, Department of Orthopaedic Surgery, National University Hospital, National University Health System, Singapore., Wong CK; Centre for Translational MR Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Chinnasamy D; National University Hospital, Department of Rehabilitation Centre, National University Health System, Singapore., Pakkiri LS; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS), Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Lee Drum C; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS), Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Wenk MR; Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore.; Precision Medicine Translational Research Program, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Totman JJ; Centre for Translational MR Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Academic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Franco-Obregón A; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Institute for Health Innovation & Technology, iHealthtech, National University of Singapore, Singapore.; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore.; Competence Center for Applied Biotechnology and Molecular Medicine, University of Zürich, Zürich, Switzerland.
Jazyk: angličtina
Zdroj: Journal of orthopaedic translation [J Orthop Translat] 2022 Oct 13; Vol. 35, pp. 99-112. Date of Electronic Publication: 2022 Oct 13 (Print Publication: 2022).
DOI: 10.1016/j.jot.2022.09.011
Abstrakt: Background: Metabolic disruption commonly follows Anterior Cruciate Ligament Reconstruction (ACLR) surgery. Brief exposure to low amplitude and frequency pulsed electromagnetic fields (PEMFs) has been shown to promote in vitro and in vivo murine myogeneses via the activation of a calcium-mitochondrial axis conferring systemic metabolic adaptations. This randomized-controlled pilot trial sought to detect local changes in muscle structure and function using MRI, and systemic changes in metabolism using plasma biomarker analyses resulting from ACLR, with or without accompanying PEMF therapy.
Methods: 20 patients requiring ACLR were randomized into two groups either undergoing PEMF or sham exposure for 16 weeks following surgery. The operated thighs of 10 patients were exposed weekly to PEMFs (1 ​mT for 10 ​min) for 4 months following surgery. Another 10 patients were subjected to sham exposure and served as controls to allow assessment of the metabolic repercussions of ACLR and PEMF therapy. Blood samples were collected prior to surgery and at 16 weeks for plasma analyses. Magnetic resonance data were acquired at 1 and 16 weeks post-surgery using a Siemens 3T Tim Trio system. Phosphorus ( 31 P) Magnetic Resonance Spectroscopy (MRS) was utilized to monitor changes in high-energy phosphate metabolism (inorganic phosphate (P i ), adenosine triphosphate (ATP) and phosphocreatine (PCr)) as well as markers of membrane synthesis and breakdown (phosphomonoesters (PME) and phosphodiester (PDE)). Quantitative Magnetization Transfer (qMT) imaging was used to elucidate changes in the underlying tissue structure, with T1-weighted and 2-point Dixon imaging used to calculate muscle volumes and muscle fat content.
Results: Improvements in markers of high-energy phosphate metabolism including reductions in ΔP i /ATP, P i /PCr and (P i  ​+ ​PCr)/ATP, and membrane kinetics, including reductions in PDE/ATP were detected in the PEMF-treated cohort relative to the control cohort at study termination. These were associated with reductions in the plasma levels of certain ceramides and lysophosphatidylcholine species. The plasma levels of biomarkers predictive of muscle regeneration and degeneration, including osteopontin and TNNT1, respectively, were improved, whilst changes in follistatin failed to achieve statistical significance. Liquid chromatography with tandem mass spectrometry revealed reductions in small molecule biomarkers of metabolic disruption, including cysteine, homocysteine, and methionine in the PEMF-treated cohort relative to the control cohort at study termination. Differences in measurements of force, muscle and fat volumes did not achieve statistical significance between the cohorts after 16 weeks post-ACLR.
Conclusion: The detected changes suggest improvements in systemic metabolism in the post-surgical PEMF-treated cohort that accords with previous preclinical murine studies. PEMF-based therapies may potentially serve as a manner to ameliorate post-surgery metabolic disruptions and warrant future examination in more adequately powered clinical trials.
The Translational Potential of This Article: Some degree of physical immobilisation must inevitably follow orthopaedic surgical intervention. The clinical paradox of such a scenario is that the regenerative potential of the muscle mitochondrial pool is silenced. The unmet need was hence a manner to maintain mitochondrial activation when movement is restricted and without producing potentially damaging mechanical stress. PEMF-based therapies may satisfy the requirement of non-invasively activating the requisite mitochondrial respiration when mobility is restricted for improved metabolic and regenerative recovery.
Competing Interests: AFO, JF and CB are inventors on patent WO 2019/17863 A1, System, and Method for Applying Pulsed Electromagnetic Fields, AFO and JF are contributors to QuantumTx Pte. Ltd., which elaborates electromagnetic field devices for human use. JZL is currently an employee of QuantumTx Pte. Ltd, but at the time of writing the manuscript was an employee of the NUS, Department of Surgery. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 The Authors.)
Databáze: MEDLINE
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