Effects of Electrical Muscle Stimulation on Skeletal Muscle During Lipopolysaccharide-Induced Inflammation: A Controlled Murine Study.
Level 5 - mechanism / opinion, no new human data
Controlled animal study
PubMed 42624470 · doi:10.1213/ANE.0000000000008260
What was done
Male C57BL/6J mice were randomly assigned to control, electrical muscle stimulation (EMS), lipopolysaccharide (LPS; 2 mg/kg intraperitoneally), or EMS plus LPS groups. EMS (80 Hz, 5 mA, 30 min) was delivered to the left hindlimb 8 hours following LPS or phosphate-buffered saline. Gastrocnemius muscle fiber cross-sectional area (CSA) was measured histologically (3 mice analyzed per group). Protein expression of Atrogin-1, MuRF1, C/EBPδ, phosphorylated mTOR, p70S6K, and STAT3 was analyzed by Western blot, and IL-6 was measured by qRT-PCR and ELISA.
What was found
Compared with control, EMS alone increased muscle fiber CSA (1610 ± 468 vs 1350 ± 437 μm2; P < .0001), phosphorylated mTOR (1.72 ± 0.234-fold; P < .0001), and p70S6K (2.34 ± 0.559-fold; P < .0001). In contrast, EMS applied under LPS inflammation failed to increase mTOR or p70S6K phosphorylation, decreased muscle fiber CSA compared with LPS alone (680 ± 327 vs 991 ± 453 μm2; P < .0001), and upregulated Atrogin-1 (13.1 ± 3.72 vs 7.85 ± 2.26-fold; p = 0.0014) and MuRF1 (3.77 ± 1.45 vs 2.50 ± 0.998-fold; p = 0.0094). EMS plus LPS also increased phosphorylated STAT3 (8.28 ± 4.16 vs 4.56 ± 1.88-fold; p = 0.0098), C/EBPδ (39.2 ± 16.4 vs 22.8 ± 12.3-fold; p = 0.0107), stimulated muscle IL-6 (335 ± 242 vs 140 ± 23.1-fold; p = 0.0095), and serum IL-6 (28.5 ± 4.60 vs 9.35 ± 3.19 ng/mL; P < .0001). Similar atrophy occurred in the contralateral non-stimulated limb.
Why it matters
These findings suggest that applying electrical muscle stimulation during active systemic inflammation may paradoxically accelerate muscle catabolism through IL-6/STAT3 signaling.
Limits
This is an acute murine model using LPS rather than clinical human sepsis. Sample size for histological analysis was small at 3 mice per group. Functional muscle strength, contractility, and long-term clinical recovery were not evaluated.
Cited by
- supports Lipopolysaccharide (LPS) administration causes extensive muscle wasting and sarcopenia over time in experimental models.