Neuromuscular Electrical Stimulation Improves Energy Substrate Metabolism and Survival in Mice With Acute Endotoxic Shock

This study investigated the therapeutic benefits of neuromuscular electrical stimulation (NMES). C57BL/6 mice were administered lipopolysaccharide (LPS; 20 mg/kg body weight) by intraperitoneal injection and divided into control (C) and NMES groups (n = 10–12 each). The latter received NMES to the bilateral gastrocnemius muscle for 1 h at low or high frequency (LF = 2 Hz and HF = 50 Hz, respectively) and low or high voltage (LV = 10 V and HV = 50 V, respectively). In LF–LV and LF–HV groups, NMES was performed twice and the results were compared with those for mice that received one round of NMES. Changes in energy metabolism were measured by indirect calorimetry up to 24 h; survival was evaluated up to 72 h after LPS administration; peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α expression in the liver and gastrocnemius muscle was evaluated by quantitative PCR; and plasma concentration of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay. Survival was improved only in the LF–LV group with one round of NMES (P < 0.01) and the LF–HV group with two rounds of NMES (P < 0.05). Fatty acid oxidation (FAO) was slightly increased in these two groups, whereas carbohydrate oxidation (CHO) was decreased or not changed. Significant upregulation of PGC-1α in muscle as well as a decrease in plasma IL-6 level were also observed in these two groups (P < 0.05). Thus, NMES exerts therapeutic effects under conditions that induce a mild switch in energy metabolism from glucose to lipid predominant metabolism through PGC-1α upregulation and suppression of inflammation, and may be an effective early intervention even in hemodynamically unstable patients.