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Vamorolone treatment improves skeletal muscle outcome in a critical illness myopathy rat model
Author(s) -
Akkad Hazem,
Cacciani Nicola,
LlanoDiez Monica,
Corpeno Kalamgi Rebeca,
Tchkonia Tamara,
Kirkland James L.,
Larsson Lars
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13172
Subject(s) - prednisolone , myopathy , muscle atrophy , intensive care unit , medicine , muscle weakness , critical illness , mechanical ventilation , atrophy , critical illness polyneuropathy , skeletal muscle , weakness , intensive care , intensive care medicine , critically ill , surgery
Aim Critical illness myopathy ( CIM ) is a consequence of modern critical care, leading to skeletal muscle atrophy/paralysis with negative consequences for mortality/morbidity and health care costs. Glucocorticoids ( GC s) have been proposed to trigger CIM . Here, we compare outcomes of two GC s, the commonly used prednisolone and the newly developed dissociative vamorolone in response to the intensive care unit ( ICU ) condition for 5 days, ie, sedation, immobilization, and mechanical ventilation. Methods Rats were divided into a 0‐day sham‐operated control group, and three groups exposed to 5 days ICU condition during treatment with prednisolone ( PRED ) or vamorolone ( VAM ) or none of these GC s ( ICU ‐group). Survival, body and muscle weights, cytokine concentrations, regulation of muscle contraction in single fast‐ and slow‐twitch muscle fibres, myofibrillar protein expression and protein degradation pathways were studied. Results Critical illness myopathy geno‐ and pheno‐types were confirmed in the ICU group. However, VAM and PRED groups showed reduced atrophy/weakness than the ICU group, and muscle specific differences with more severe negative effects on fast‐twitch muscle fibres in the PRED than the other groups. Conclusion These results show that vamorolone provides a GC intervention superior to typical GC s in improving CIM outcomes. Further, the findings do not support the notion that moderate‐dose GC treatment represents a factor triggering CIM .