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- Kristen T Crowell and Charles H Lang.
- Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania.
- Shock. 2021 May 1; 55 (5): 649-659.
AbstractConvalescence in humans after severe sepsis occurs over weeks to months and is associated with prolonged functional disabilities and impaired quality-adjusted survival. While much is known regarding the acute early phase of sepsis, there is a knowledge gap pertaining to restoration of muscle mass and function after elimination of the septic nidus. We used a sepsis-recovery model-where cecal-ligation-puncture (CLP) was performed in adult male mice followed 24 h later by removal of the cecum and antibiotic treatment-to assess changes in the abundance of muscle contractile proteins and function during the acute phase of sepsis (24 h post-CLP) and during the recovery phase (day 10 post-CLP). Although body weight and food consumption decreased acutely with sepsis, both had normalized by day 10; however, extensor digitorum longus mass remained decreased 10%. During acute sepsis, there were few contractile defects or significant changes in contractile proteins. In contrast, during sepsis recovery, specific maximum isometric twitch and specific maximum tetanic force were decreased ≈50%, compared with time-matched pair-fed controls, and defects were independent of the concomitant reduction in muscle mass. Force generation in sepsis-recovery mice was decreased 30% with increasing stimulus frequency. Contractile defects during sepsis-recovery were associated with 50% to 90% reductions in thin filament (troponin T, troponin I, tropomyosin, α-sarcomeric actin), thick filament (myosin heavy and myosin light chains), Z-disc (α-actinin 3), and M-band (myomesin-2) proteins, but no change in the intermediate filaments desmin and vimentin. During sepsis recovery, myofibrillar protein synthesis did not differ from control, but synthesis of sarcoplasmic proteins was increased 60%. These data suggest intrinsic defects in muscle contractile function exist during the recovery phase of sepsis and may negatively impact convalescence.Copyright © 2020 by the Shock Society.
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