title: Sparing of muscle mass and function by passive loading in an experimental intensive care unit model.
abstract: The response to mechanical stimuli, i.e., tensegrity, plays an important role in regulating cell physiological and pathophysiological function, and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims to unravel the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long-term (weeks) time-resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. 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 versus the unloaded muscles after a 2-week ICU intervention. We demonstrate that the improved maintenance of muscle mass and function is probably a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, 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, extracellular matrix/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
authors.affiliation: Department of Neuroscience, Clinical Neurophysiology, University Hospital, Entrance 85, 3rd floor, SE-751 85 Uppsala, Sweden.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Renaud
authors.forename: Monica
authors.initials: M
authors.lastname: Llano-Diez
authors.forename: Barbara
authors.initials: B
authors.lastname: Ravara
authors.forename: Luisa
authors.initials: L
authors.lastname: Gorza
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Jin
authors.forename: Nicola
authors.initials: N
authors.lastname: Cacciani
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Gustafson
authors.forename: Julien
authors.initials: J
authors.lastname: Ochala
authors.forename: Rebeca
authors.initials: R
authors.lastname: Corpeno
authors.forename: Meishan
authors.initials: M
authors.lastname: Li
authors.forename: Yvette
authors.initials: Y
authors.lastname: Hedström
authors.forename: G Charles
authors.initials: GC
authors.lastname: Ford
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Lars
authors.initials: L
authors.lastname: Larsson
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003422:Critical Care; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007103:Immobilization; D009119:Muscle Contraction; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009218:Myosins / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D026741:Physical Therapy Modalities; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050050:Protein Carbonylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013997:Time Factors
chemical_list: D046988:Proteasome Endopeptidase Complex; D009218:Myosins