Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients
dc.contributor.author | Jameson, TSO | |
dc.contributor.author | Caldow, MK | |
dc.contributor.author | Stephens, F | |
dc.contributor.author | Denehy, L | |
dc.contributor.author | Lynch, GS | |
dc.contributor.author | Koopman, R | |
dc.contributor.author | Krajcova, A | |
dc.contributor.author | Urban, T | |
dc.contributor.author | Berney, S | |
dc.contributor.author | Duska, F | |
dc.contributor.author | Puthucheary, Z | |
dc.date.accessioned | 2023-12-13T09:36:37Z | |
dc.date.issued | 2023-11-06 | |
dc.date.updated | 2023-12-12T19:46:31Z | |
dc.description.abstract | BACKGROUND: Critically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function. METHODS: Primary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty. Validation cohort: Four-centre randomized controlled trial. INTERVENTION: FES cycling for 60-90min/day. ANALYSES: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation. RESULTS: Positively enriched pathways between healthy volunteers and ICU participants were "stress response", "response to stimuli" and "protein metabolism", in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were "FOXO-mediated transcription" (admission = 0.48 ± 0.94, day 7 = - 0.47 ± 1.04 mean log2 fold change; P = 0.042), "Fatty acid metabolism" (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2 fold change; P = 0.042) and "Interleukin-1 processing" (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2 fold change; P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P < 0.001), SLC25A20 (P = 0.017) and UCP3 (P < 0.001) decreased between admission and day 7 in both arms. LPIN-1 (P < 0.001) and SPT1 (P = 0.044) decreased between admission and day 7. IL-18 (P = 0.011) and TNFRSF12A (P = 0.009) increased in both arms between admission and day 7. IL-1β (P = 0.007), its receptor IL-1R1 (P = 0.005) and IL-6R (P = 0.001) decreased in both arms between admission and day 7. No between group differences were seen in any of these (all p > 0.05). CONCLUSIONS: Intramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone. | en_GB |
dc.description.sponsorship | Czech Ministry of Health and the National Health | en_GB |
dc.description.sponsorship | Czech Ministry of Health and the National Health | en_GB |
dc.description.sponsorship | National Health and Medical Research Council of Australia | en_GB |
dc.description.sponsorship | Johns Hopkins University | en_GB |
dc.description.sponsorship | Intensive Care Foundation of Australia | en_GB |
dc.description.sponsorship | Austin Health Medical Research Fund | en_GB |
dc.identifier.citation | Vol. 27, No. 1, article 428 | en_GB |
dc.identifier.doi | https://doi.org/10.1186/s13054-023-04664-7 | |
dc.identifier.grantnumber | 16-28663A | en_GB |
dc.identifier.grantnumber | NU21J-06-00078 of AZV | en_GB |
dc.identifier.grantnumber | App1079460 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/134781 | |
dc.identifier | ORCID: 0000-0001-6312-5351 (Stephens, F) | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/37932834 | en_GB |
dc.rights | © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | en_GB |
dc.subject | Critical illness | en_GB |
dc.subject | Exercise | en_GB |
dc.subject | Gene expression | en_GB |
dc.subject | Muscle wasting | en_GB |
dc.subject | Rehabilitation | en_GB |
dc.title | Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-12-13T09:36:37Z | |
dc.identifier.issn | 1364-8535 | |
exeter.article-number | 428 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from BMC via the DOI in this record. | en_GB |
dc.description | Availability of data and materials: Source data can be obtained from the corresponding author upon reasonable request. | en_GB |
dc.identifier.eissn | 1466-609X | |
dc.identifier.journal | Critical Care | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-09-26 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-11-06 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-12-13T09:31:06Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-12-13T09:36:48Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-11-06 |
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