Metabolic phenotype of skeletal muscle in early critical illness

Zudin Puthucheary ,Paul L Greenhaff ,Philip J Atherton ,L.d Calvert ,Sean Manning ,Michael Steiner ,Lindsay M Edwards ,Mervyn Singer ,Saima Saeed ,Kenneth Smith ,Elaine Holmes ,Nicholas Hart ,Cristiana P Velloso ,Danielle E Bear ,Rónan Astin ,Rachel L Batterham ,Y A Zahed Pasha ,María José Gómez-Romero ,Despina Constantin ,Stephen Harridge ,Mark Mcphail ,Hugh Montgomery

doi:10.1136/thoraxjnl-2017-211073

Abstract

ObjectivesTo characterise the sketetal muscle metabolic phenotype during early critical illness.MethodsVastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male,...

Highlights

IntroductionAcute skeletal muscle wasting occurs early and rapidly in critical illness[1] and is reported to be a Key messagesWhat is the key question? ►► To investigate if ATP bioavailability and lipid metabolism are drivers of the early and rapidly acute skeletal muscle wasting that occurs during critical illness.What is the bottom line? ►► In this first study to investigate the relationship between bioenergetics changes and skeletal muscle wasting during early critical illness, alterations in fat metabolism and ATP abundance are associated with the severity of inflammation and altered oxygen signalling, which could be considered as targets for future therapies.Why read on? ►► Skeletal muscle wasting in critical care is associated with impaired lipid oxidation and reduced ATP bioavailability, driven by intramuscular inflammation and altered hypoxic signalling, which may account for the inconsistent outcome observed in the nutrition and exercise clinical trials.major driver of long-term disability.[2]
Measurements and main results From day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger messenger RNA (mRNA) expression (−27.4CN; n=23; p=0.025) and mitochondrial DNA copy number (−1859CN (IQR −5557–1325); n=35; p=0.032)
What is the bottom line? ►► In this first study to investigate the relationship between bioenergetics changes and skeletal muscle wasting during early critical illness, alterations in fat metabolism and ATP abundance are associated with the severity of inflammation and altered oxygen signalling, which could be considered as targets for future therapies

Summary

Introduction

Acute skeletal muscle wasting occurs early and rapidly in critical illness[1] and is reported to be a Key messagesWhat is the key question? ►► To investigate if ATP bioavailability and lipid metabolism are drivers of the early and rapidly acute skeletal muscle wasting that occurs during critical illness.What is the bottom line? ►► In this first study to investigate the relationship between bioenergetics changes and skeletal muscle wasting during early critical illness, alterations in fat metabolism and ATP abundance are associated with the severity of inflammation and altered oxygen signalling, which could be considered as targets for future therapies.Why read on? ►► Skeletal muscle wasting in critical care is associated with impaired lipid oxidation and reduced ATP bioavailability, driven by intramuscular inflammation and altered hypoxic signalling, which may account for the inconsistent outcome observed in the nutrition and exercise clinical trials.major driver of long-term disability.[2]. ►► To investigate if ATP bioavailability and lipid metabolism are drivers of the early and rapidly acute skeletal muscle wasting that occurs during critical illness. ►► Skeletal muscle wasting in critical care is associated with impaired lipid oxidation and reduced ATP bioavailability, driven by intramuscular inflammation and altered hypoxic signalling, which may account for the inconsistent outcome observed in the nutrition and exercise clinical trials. Major driver of long-term disability.[2] muscle wasting is associated with increased length of intensive care unit (ICU) stay,[1] hospital stay[1] and mortality.[3] It is underpinned by a fall in muscle protein synthesis,[1] a process which, in healthy individuals, is responsive to exercise and amino acid loading.[4] clinical trials of enhanced nutritional support[5,6,7,8] and early exercise training[9,10,11,12] in acute critical illness have yielded inconsistent results in terms of amelioration of muscle wasting and improvement in physical function

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