Preventive effects of kilohertz frequency electrical stimulation on sepsis-induced muscle atrophy

Area of Science:

• Biomedical Engineering
• Physiology
• Molecular Biology

Background:

• Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
• Sepsis frequently leads to muscle atrophy, contributing to prolonged recovery and increased morbidity.
• The ubiquitin-proteasome pathway plays a critical role in the catabolism of muscle proteins during sepsis.

Purpose of the Study:

• To investigate the efficacy of kilohertz frequency electrical stimulation (ES) in preventing muscle atrophy induced by sepsis.
• To evaluate the impact of ES on muscle mass, fiber cross-sectional area, and specific molecular markers of muscle degradation.

Main Methods:

• Sepsis was induced in male ICR mice using lipopolysaccharide (LPS) injection over four days.
• Mice were divided into control, LPS-induced sepsis, and LPS with ES treatment groups.
• Muscle atrophy was assessed by measuring tibialis anterior muscle weight, fiber cross-sectional area (CSA), and analyzing inflammatory cytokines and ubiquitinated proteins via ELISA and Western blot.

Main Results:

• LPS injection significantly increased inflammatory cytokines and induced muscle mass loss (-29.0%) and decreased fiber CSA.
• Electrical stimulation (ES) attenuated sepsis-induced muscle mass loss (-23.1%) and preserved fiber CSA.
• ES treatment also reduced the upregulation of atrogin-1 and ubiquitinated proteins in the tibialis anterior muscle.

Conclusions:

• Kilohertz frequency electrical stimulation demonstrates a protective effect against sepsis-induced muscle atrophy.
• ES may exert its beneficial effects by inhibiting the ubiquitin-proteasome pathway, a key mechanism in muscle protein degradation.
• These findings suggest ES as a potential therapeutic strategy to combat muscle wasting in sepsis patients.