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Series GSE37944 Query DataSets for GSE37944
Status Public on May 12, 2012
Title Sparing of muscle mass and function by passive loading in an experimental intensive care unit model
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
 
Overall design This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days.
A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) α-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80°C. RNA was extracted.
 
Contributor(s) Llano-Diez M, Renaud G, Ravara B, Gorza L, Larsson L, Feng HZ, Jin JP, Cachiani N, Gustafsson AM, Li M, Hedström Y, Ford GC, Nair KS
Citation(s) 23266938
Submission date May 11, 2012
Last update date Nov 06, 2013
Contact name Monica Llano-Diez
Organization name Uppsala university
Department Neuroscience
Lab Clinical neurophysilogy
Street address Akademiska sjukhuset, Ing.85, 3tr
City Uppsala
ZIP/Postal code 75185
Country Sweden
 
Platforms (1)
GPL6247 [RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version]
Samples (46)
GSM930471 Muscle_AQM_6h-4d_unloaded_U11
GSM930472 Muscle_AQM_6h-4d_unloaded_UU13
GSM930473 Muscle_AQM_6h-4d_unloaded_UU15
Relations
BioProject PRJNA165713

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Supplementary file Size Download File type/resource
GSE37944_RAW.tar 184.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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