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Weak by the Machines: Muscle Motor Protein Dysfunction ‐NDASH‐ a side Effect of Intensive Care Unit Treatment

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Acta Physiologica

Published online on


Intensive care interventions involve periods of mechanical ventilation, sedation and complete mechanical silencing of patients. Critical illness myopathy (CIM) is an ICU‐acquired myopathy that is associated with limb muscle weakness, muscle atrophy, electrical silencing of muscle and motor‐proteinopathy. The hallmark of CIM is a preferential muscle myosin loss due to increased catabolic and reduced anabolic activity. The ubiquitin‐proteasome pathway plays an important role, apart from recently identified novel mechanisms affecting nonlysosomal protein degradation or autophagy. CIM is not reproduced by pure disuse atrophy, denervation atrophy, steroid‐induced atrophy or septic myopathy, although combinations of high‐dose steroids and denervation can mimic CIM. Novel animal models of critical illness and ICU‐treatment (i.e. mechanical ventilation and complete immobilization) provide novel insights regarding the time course of protein synthesis and degradation alterations, and the role of protective chaperone activities in the process of myosin loss. Altered mechano‐signaling seems involved in triggering a major part of myosin loss in experimental CIM models and passive loading of muscle potently ameliorates the CIM phenotype. We provide a systematic overview of similarities and distinct differences in the signaling pathways involved in triggering muscle atrophy in CIM and isolated trigger factors. Since preferential myosin loss is mostly determined from biochemistry analyses providing no spatial resolution of myosin loss processes within myofibres, we also provide first results monitoring myosin signal intensities during experimental ICU‐intervention using multiphoton Second harmonic Generation microscopy. Our results confirm that myosin loss is an evenly distributed process within myofibres rather than being confined to hot spots. This article is protected by copyright. All rights reserved.