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Critical Illness Myopathy (CIM) and Ventilator‐Induced Diaphragm Muscle Dysfunction (VIDD): Acquired Myopathies Affecting Contractile Proteins

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ABSTRACT

Critical care and intensive care units (ICUs) have undergone dramatic changes and improvements in recent years, and critical care is today one of the fastest growing hospital disciplines. Significant improvements in treatments, removal of inefficient and harmful interventions, and introduction of advanced technological support systems have improved survival among critically ill ICU patients. However, the improved survival is associated with an increased number of patients with complications related to modern critical care. Severe muscle wasting and impaired muscle function are frequently observed in immobilized and mechanically ventilated ICU patients. Approximately 30% of mechanically ventilated and immobilized ICU patients for durations of five days and longer develop generalized muscle paralysis of all limb and trunk muscles. These patients typically have intact sensory and cognitive functions, a condition known as critical illness myopathy (CIM). Mechanical ventilation is a lifesaving treatment in critically ill ICU patients; however, the being on a ventilator creates dependence, and the weaning process occupies as much as 40% of the total time of mechanical ventilation. Furthermore, 20% to 30% of patients require prolonged intensive care due to ventilator‐induced diaphragm dysfunction (VIDD), resulting in poorer outcomes, and greatly increased costs to health care providers. Our understanding of the mechanisms underlying both CIM and VIDD has increased significantly in the past decade and intervention strategies are presently being evaluated in different experimental models. This short review is restricted CIM and VIDD pathophysiology rather than giving a comprehensive review of all acquired muscle wasting conditions associated with modern critical care. © 2017 American Physiological Society. Compr Physiol 7:105‐112, 2017.

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Figure 1. Figure 1. Myofibrillar protein isoform composition (A). Chemically skinned single muscle cells from the tibialis anterior muscle from a normal control subject (a) and a patient with CIM (b) in relaxing solution (Relax) and during maximum activation (pCa 4.5). Scale bar, 50 μm. (B) Electrophoretic separation of myosin heavy chain (MyHC) isoforms by 6% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). MyHCs were separated from single tibial anterior fiber segments (lanes 1‐5, 7‐10), bundles of 10 tibial anterior fibers (lanes 11, 12) and from single 10 μm cross‐section from a vastus lateralis muscle biopsy (lanes 6, 13) expressing three MyHCs bands (types I, IIa, and IIx). Lanes 9 to 12 are from the quadriplegic patient (lane 10 corresponds to the fiber b above, A) and the other lanes are from normal control subjects. (C) Electrophoretic separation of thick‐ and thin‐filament protein isoforms with 12% SDS‐PAGE. Fibers 1 to 3 are from the tibialis anterior muscle of a patient with hemi paresis due to an upper motoneuron lesion. Lane 1 from the paretic side and lanes 2 and 3 from the nonparetic normal side. Lanes 4 and 5 (encircled in red) correspond to the fiber bundles from the quadriplegic patient, that is, the same bundles as lanes 11 and 12 (encircled in red) on the 6% SDS‐PAGE (B). Modified, with permission, from Larsson and Roland ().
Figure 2. Figure 2. Possible mechanisms of action of BGP‐15 in response to nicotinamide adenine dinucleotide hydride (NADH) oxidase and ROS production. Modified, with permission, from Crul et al. ().


Figure 1. Myofibrillar protein isoform composition (A). Chemically skinned single muscle cells from the tibialis anterior muscle from a normal control subject (a) and a patient with CIM (b) in relaxing solution (Relax) and during maximum activation (pCa 4.5). Scale bar, 50 μm. (B) Electrophoretic separation of myosin heavy chain (MyHC) isoforms by 6% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). MyHCs were separated from single tibial anterior fiber segments (lanes 1‐5, 7‐10), bundles of 10 tibial anterior fibers (lanes 11, 12) and from single 10 μm cross‐section from a vastus lateralis muscle biopsy (lanes 6, 13) expressing three MyHCs bands (types I, IIa, and IIx). Lanes 9 to 12 are from the quadriplegic patient (lane 10 corresponds to the fiber b above, A) and the other lanes are from normal control subjects. (C) Electrophoretic separation of thick‐ and thin‐filament protein isoforms with 12% SDS‐PAGE. Fibers 1 to 3 are from the tibialis anterior muscle of a patient with hemi paresis due to an upper motoneuron lesion. Lane 1 from the paretic side and lanes 2 and 3 from the nonparetic normal side. Lanes 4 and 5 (encircled in red) correspond to the fiber bundles from the quadriplegic patient, that is, the same bundles as lanes 11 and 12 (encircled in red) on the 6% SDS‐PAGE (B). Modified, with permission, from Larsson and Roland ().


Figure 2. Possible mechanisms of action of BGP‐15 in response to nicotinamide adenine dinucleotide hydride (NADH) oxidase and ROS production. Modified, with permission, from Crul et al. ().
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How to Cite

Lars Larsson, Oliver Friedrich. Critical Illness Myopathy (CIM) and Ventilator‐Induced Diaphragm Muscle Dysfunction (VIDD): Acquired Myopathies Affecting Contractile Proteins. Compr Physiol 2016, 7: 105-112. doi: 10.1002/cphy.c150054