Gene expression and muscle fiber function in a porcine ICU model.
Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to 1) the poorly understood intricate cellular and molecular networks and 2) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a 5-day period. Among the differentially regulated transcripts, extracellular matrix, energy metabolism, sarcomeric and LIM protein mRNA levels were downregulated, while ubiquitin proteasome system, cathepsins, oxidative stress responsive genes and heat shock proteins (HSP) mRNAs were upregulated. Despite 5 days of immobilization and mechanical ventilation single muscle fiber cross-sectional areas as well as the maximum force generating capacity at the single muscle fiber level were preserved. It is proposed that HSP induction in skeletal muscle is an inherent, primary, but temporary protective mechanism against protein degradation. To our knowledge, this is the first study that isolates the effect of immobilization and mechanical ventilation in an ICU condition from various other cofactors.
Banduseela
Varuna C
VC
Department of Clinical Neurophysiology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Ochala
Julien
J
Chen
Yi-Wen
YW
Göransson
Hanna
H
Norman
Holly
H
Radell
Peter
P
Eriksson
Lars I
LI
Hoffman
Eric P
EP
Larsson
Lars
L
D000818:Animals; D001706:Biopsy; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007103:Immobilization; D015151:Immunoblotting; D007362:Intensive Care Units; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D012121:Respiration, Artificial; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D013997:Time Factors
D006360:Heat-Shock Proteins