Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model

Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

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2 Citations (Scopus)

Abstract

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed.

Original languageEnglish
Article numbere49920
JournaleLife
Volume8
DOIs
Publication statusPublished - 12-2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Owen, A. M., Patel, S. P., Smith, J. D., Balasuriya, B. K., Mori, S. F., Hawk, G. S., Stromberg, A. J., Kuriyama, N., Kaneki, M., Rabchevsky, A. G., Butterfield, T. A., Esser, K. A., Peterson, C. A., Starr, M. E., & Saito, H. (2019). Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model. eLife, 8, [e49920]. https://doi.org/10.7554/eLife.49920