• D Clark Files, Kunhong Xiao, Tan Zhang, Chun Liu, Jiang Qian, Weiling Zhao, Peter E Morris, Osvaldo Delbono, and Xin Feng.
• Internal Medicine-Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America ; Wake Forest Critical Care Translational Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
• Plos One. 2014 Jan 1; 9 (1): e87587.

BackgroundSkeletal muscle wasting in acute lung injury (ALI) patients increases the morbidity and mortality associated with this critical illness. The contribution of laryngeal muscle wasting to these outcomes is unknown, though voice impairments and aspiration are common in intensive care unit (ICU) survivors. We evaluated the intrinsic laryngeal abductor (PCA, posterior cricoarytenoid), adductor (CT, cricothyroid) and limb (EDL, extensor digitorum longus) muscles in a mouse model of ALI.MethodsEscherichia coli lipopolysaccharides were instilled into the lungs of adult male C57Bl6J mice (ALI mice). Limb and intrinsic laryngeal muscles were analyzed for fiber size, type, protein expression and myosin heavy chain (MyHC) composition by SDS-PAGE and mass spectroscopy.ResultsMarked muscle atrophy occurred in the CT and EDL muscles, while the PCA was spared. The E3 ubiquitin ligase muscle ring finger-1 protein (MuRF1), a known mediator of limb muscle atrophy in this model, was upregulated in the CT and EDL, but not in the PCA. Genetic inhibition of MuRF1 protected the CT and EDL from ALI-induced muscle atrophy. MyHC-Extraocular (MyHC-EO) comprised 27% of the total MyHC in the PCA, distributed as hybrid fibers throughout 72% of PCA muscle fibers.ConclusionThe vocal cord abductor (PCA) contains a large proportion of fibers expressing MyHC-EO and is spared from muscle atrophy in ALI mice. The lack of MuRF1 expression in the PCA suggests a previously unrecognized mechanism whereby this muscle is spared from atrophy. Atrophy of the vocal cord adductor (CT) may contribute to the impaired voice and increased aspiration observed in ICU survivors. Further evaluation of the sparing of muscles involved in systemic wasting diseases may lead to potential therapeutic targets for these illnesses.

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