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Dynamics of myosin degradation in intensive care unit-acquired weakness during severe critical illness

Tobias Wollersheim| Janine Woehlecke| Martin Krebs| Jida Hamati| Doerte Lodka| Anja Luther-Schroeder| Claudia Langhans| Kurt Haas| Theresa Radtke| Christian Kleber| Claudia Spies| Siegfried Labeit| Markus Schuelke| Simone Spuler| Joachim Spranger| Steffen Weber-Carstens| Jens Fielitz
Original
Volume 40, Issue 4 / April , 2014

Pages 528 - 538

Abstract

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.

Keywords

References

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