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Metabolic phenotype of skeletal muscle in early critical illness

Puthucheary, ZA; Astin, R; Mcphail, MJW; Saeed, S; Pasha, Y; Bear, DE; Constantin, D; ... Montgomery, HE; + view all (2018) Metabolic phenotype of skeletal muscle in early critical illness. Thorax 10.1136/thoraxjnl-2017-211073. (In press). Green open access

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Abstract

OBJECTIVES: To characterise the sketetal muscle metabolic phenotype during early critical illness. METHODS: Vastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5). MEASUREMENTS AND MAIN RESULTS: From day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (-27.4CN (95% CI -123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (-1859CN (IQR -5557-1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (-4.8 mmol/kg dw (IQR -8.0-1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR -0.09-2.6); n=31; p<0.001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5-1672); n=15; p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR -0.44-3.33); n=29; p=0.041) and IL-10 (13.6 ng (IQR 3.4-39.0); n=29; p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7); p<0.001) and ghrelin (16.0 ng/mL (IQR -7-100); p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered. CONCLUSIONS: Decreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting. TRIAL REGISTRATION NUMBER: NCT01106300.

Type: Article
Title: Metabolic phenotype of skeletal muscle in early critical illness
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/thoraxjnl-2017-211073
Publisher version: http://doi.org/10.1136/thoraxjnl-2017-211073
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ARDS, respiratory muscles
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Metabolism and Experi Therapeutics
URI: https://discovery.ucl.ac.uk/id/eprint/10052836
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