Contractility and Myofibrillar Content in Skeletal Muscle are Decreased During Post-Sepsis Recovery, But Not During the Acute Phase of Sepsis

• Published in: Shock (Augusta, Ga.) Vol. 55; no. 5; p. 649
• Main Authors: Crowell, Kristen T, Lang, Charles H
• Format: Journal Article
• Language: English
• Published: United States 01.05.2021
• Subjects: Acute Disease; Animals; Male; Mice; Mice, Inbred C57BL; Muscle Contraction; Muscle, Skeletal - physiopathology; Muscle, Skeletal - ultrastructure; Myofibrils; Recovery of Function; Sepsis - physiopathology; Time Factors
• ISSN: 1540-0514
• DOI: 10.1097/SHK.0000000000001555

Convalescence 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.