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.

• Klíčová slova
• Critical illness, Exercise, Gene expression, Muscle wasting, Rehabilitation,
• MeSH
• elektrická stimulace MeSH
• interleukin-18 * MeSH
• jednotky intenzivní péče MeSH
• kritický stav * MeSH
• lidé MeSH
• mastné kyseliny MeSH
• membránové transportní proteiny MeSH
• messenger RNA MeSH
• svalová atrofie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-18 * MeSH
• mastné kyseliny MeSH
• membránové transportní proteiny MeSH
• messenger RNA MeSH
• SLC25A20 protein, human MeSH Prohlížeč

BACKGROUND: Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome. METHODS: An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. PRIMARY OUTCOME: quality of life measured by 36-Item Short Form Health Survey score at 6 months. SECONDARY OUTCOMES: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.

• Klíčová slova
• Critically ill, Early rehabilitation, Functional electrical stimulation-assisted cycle ergometry, Intensive care unit, Mobility, Physical therapy,
• MeSH
• časové faktory MeSH
• cyklistika * MeSH
• elektrostimulační terapie * škodlivé účinky   MeSH
• ergometrie * MeSH
• jednotky intenzivní péče MeSH
• kosterní svaly inervace   MeSH
• kritický stav MeSH
• kvalita života MeSH
• lidé MeSH
• obnova funkce MeSH
• pragmatické klinické studie jako téma MeSH
• svalová kontrakce * MeSH
• svalová síla * MeSH
• svalová slabost diagnóza   patofyziologie   rehabilitace   MeSH
• výsledek terapie MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH