Sparing of muscle mass and function by passive loading in an experimental intensive care unit model
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Sparing of muscle mass and function by passive loading in an experimental intensive care unit model. / Renaud, Guillaume; Llano-Diez, Monica; Ravara, Barbara; Gorza, Luisa; Feng, Han Zhong; Jin, Jian Ping; Cacciani, Nicola; Gustafson, Ann Marie; Ochala, Julien; Corpeno, Rebeca; Li, Meishan; Hedström, Yvette; Ford, G. Charles; Nair, K. Sreekumaran; Larsson, Lars.
In: Journal of Physiology, Vol. 591, No. 5, 03.2013, p. 1385-1402.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sparing of muscle mass and function by passive loading in an experimental intensive care unit model
AU - Renaud, Guillaume
AU - Llano-Diez, Monica
AU - Ravara, Barbara
AU - Gorza, Luisa
AU - Feng, Han Zhong
AU - Jin, Jian Ping
AU - Cacciani, Nicola
AU - Gustafson, Ann Marie
AU - Ochala, Julien
AU - Corpeno, Rebeca
AU - Li, Meishan
AU - Hedström, Yvette
AU - Ford, G. Charles
AU - Nair, K. Sreekumaran
AU - Larsson, Lars
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874447722&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2012.248724
DO - 10.1113/jphysiol.2012.248724
M3 - Journal article
C2 - 23266938
AN - SCOPUS:84874447722
VL - 591
SP - 1385
EP - 1402
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 5
ER -
ID: 245663650