Dworkin, Barry R.

The muscle wasting and impaired muscle function associated with critical llness in ICU patients have negative consequences for recovery from primary disease, but are also the most persistent and debilitating of problems for ICU survivors years after hospital discharge. This study aims at improving our understanding of the mechanisms underlying the muscle wasting in ICU patients by conducting time‐resolved analyses of skeletal muscle structure and function together with measurements of protein synthesis rate, myofibrillar protein and gene expression and intracellular signaling in response to post‐synaptic block of neuromuscular transmission (NMB), sedation, mechanical ventilation and muscle unloading at durations varying from hours to two wks by using a unique experimental rat ICU model. Skeletal muscle structure and function were well maintained during the first four days, followed by a dramatic and progressive decline in muscle size and function. The preferential loss of the molecular motor protein myosin and impaired forcegenerating capacity (specif force) are the major causes underlying the impaired skeletal muscle function in the ICU model. Muscle unloading due to lack of weightbearing (external unloading) and muscle membrane depolarization (internal unloading) are forwarded as very important underlying factors. Supported by the Sweish Research Council and AFM