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Physical inactivity and muscle weakness in the critically ill

Chambers, Melissa A. PhD; Moylan, Jennifer S. PhD; Reid, Michael B. PhD

doi: 10.1097/CCM.0b013e3181b6e974
Scientific Reviews

Patients in the intensive care unit commonly develop muscle weakness. In part, this reflects loss of mechanical loading due to physical inactivity, bed rest, or immobilization. Mechanical unloading stimulates a complex adaptive response that results in muscle atrophy and loss of specific force. One element of this response is slowing of protein synthesis, which is regulated by signaling pathways downstream of mammalian target of rapamycin and insulin-like growth factor-1. In parallel, protein degradation is accelerated via three coordinate processes: calcium-dependent proteolysis, adenosine triphosphate-dependent proteolysis, and lysosomal proteolysis. Finally, unloading stimulates apoptosis of a subset of myonuclei within multinucleated muscle fibers. This helps to stabilize the relationship between nuclear number and cell volume during atrophy. Each of these responses is promoted by concurrent development of oxidative stress caused by increased production of reactive oxygen species in unloaded muscle fibers. Countermeasures that lessen the effects of unloading include physical activity, nutritional supplements, hormone therapy, and antioxidant administration. Targeted research is needed to define the role of mechanical unloading in intensive care unit-associated weakness and develop countermeasures to preserve muscle function, lessen illness, and hasten the recovery of critically ill patients.

From the Department of Physiology, University of Kentucky, Lexington, KY.

Our work in this area is supported, in part, by the National Space Biomedical Research Institute through National Aeronautics and Space Administration Grant NC9-58 (MBR) and an American Heart Association predoctoral fellowship (MAC). Dr. Reid has received funding from National Aeronautics and Space Administration and the American Heart Association. Drs. Chambers and Moylan have received funding from the National Institutes of Health.

The authors have not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins