• Sarah Derde, Greet Hermans, Inge Derese, Fabian Güiza, Yvette Hedström, Pieter J Wouters, Frans Bruyninckx, André D'Hoore, Lars Larsson, Greet Van den Berghe, and Ilse Vanhorebeek.
• Departments of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
• Crit. Care Med.. 2012 Jan 1;40(1):79-89.

ObjectiveMuscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and denervation, and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness.DesignSecondary analysis of two large, prospective, single-center randomized clinical studies.SettingUniversity hospital surgical and medical intensive care unit.PatientsCritically ill patients and matched controls.InterventionsIntensive care unit patients had been randomized to blood glucose control to 80-110 mg/dL with insulin infusion or conventional glucose management, where insulin was only administered when glucose levels rose above 215 mg/dL.Measurements And Main ResultsAs compared with controls, rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size, decreased mRNA levels for myofibrillar proteins, increased proteolytic enzyme activities, and a lower myosin/actin ratio, virtually irrespective of insulin therapy. Increased forkhead box O1 action may have played a role. Most alterations were more severe in patients treated with corticosteroids. Duration of corticosteroid treatment, independent of duration of intensive care unit stay or other risk factors, was a dominant risk factor for a low myosin/actin ratio. The immature acetylcholine receptor subunit γ messenger RNA expression was elevated in vastus lateralis, independent of the myosin/actin ratio.ConclusionsBoth limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis. This affected myosin to a greater extent than actin, resulting in a decreased myosin/actin ratio. Muscle atrophy was not ameliorated by intensive insulin therapy, but possibly aggravated by corticosteroids.

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