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Erschienen in:
01.04.2014 | Original
Dynamics of myosin degradation in intensive care unit-acquired weakness during severe critical illness
Erschienen in: Intensive Care Medicine | Ausgabe 4/2014
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Importance
Intensive care unit (ICU)-acquired muscle wasting is a devastating complication leading to persistent weakness and functional disability. The mechanisms of this myopathy are unclear, but a disturbed balance of myosin heavy chain (MyHC) is implicated.
Objective
To investigate pathways of myosin turnover in severe critically ill patients at high risk of ICU-acquired weakness.
Design
Prospective, mechanistic, observational study.
Setting
Interdisciplinary ICUs of a university hospital.
Participants
Twenty-nine patients with Sequential Organ Failure Assessment (SOFA) scores of at least 8 on three consecutive days within the first 5 days in ICU underwent two consecutive open skeletal muscle biopsies from the vastus lateralis at median days 5 and 15. Control biopsy specimens were from healthy subjects undergoing hip-replacement surgery.
Interventions
None.
Main outcome(s) and measure(s)
Time-dependent changes in myofiber architecture, MyHC synthesis, and degradation were determined and correlated with clinical data.
Results
ICU-acquired muscle wasting was characterized by early, disrupted myofiber ultrastructure followed by atrophy of slow- and fast-twitch myofibers at later time points. A rapid decrease in MyHC mRNA and protein expression occurred by day 5 and persisted at day 15 (P < 0.05). Expression of the atrophy genes MuRF-1 and Atrogin1 was increased at day 5 (P < 0.05). Early MuRF-1 protein content was closely associated with late myofiber atrophy and the severity of weakness.
Conclusions and relevance
Decreased synthesis and increased degradation of MyHCs contribute to ICU-acquired muscle wasting. The rates and time frames suggest that pathogenesis of muscle failure is initiated very early during critical illness. The persisting reduction of MyHC suggests that sustained treatment is required.