High-intensity interval training using electrical stimulation improves mitochondrial dysfunction and muscle endurance in rats with chronic kidney disease.

Abstract

Mitochondrial dysfunction in skeletal muscle has recently been highlighted as a major pathophysiological factor of chronic kidney disease (CKD)-associated muscle fatigue. However, effective therapeutic interventions to improve mitochondrial function have not been established. Here we examined the effects of high-intensity interval training (HIIT) using electrical stimulation (ES) intervention on skeletal muscle in CKD rats. CKD was induced by 5/6 nephrectomy (Nx) in male Wistar rats, and sham-operated rats served as controls (Sham). We defined the left leg of Nx rat trained with HIIT as the Nx-HIIT leg and the untrained right leg as the Nx-CNT leg. HIIT was enforced by electrically stimulating plantar flexor muscles every other day for 4 weeks. In vivo muscle endurance analysis using repeated fatiguing stimulation measured 24 h after the last training session showed a significantly greater force depression in the Nx-CNT leg compared to that in the Sham leg, which was significantly improved in the Nx-HIIT leg. Pyruvate/malate-driven ADP- and uncoupler-stimulated mitochondrial respiration in isolated muscle mitochondria from the Nx-CNT leg assessed by Seahorse XFe96 analyzer were significantly decreased compared with those from the Sham leg, which were also significantly recovered in those of the Nx-HIIT leg. Consistent with improved mitochondrial function, myosin heavy chain (MyHC) electrophoresis showed a significant increase in the proportion of fast-twitch MyHC IIB fibers in the Nx-CNT leg compared to that in the Sham and the Nx-HIIT leg. HIIT with ES improved muscle fatigue and mitochondrial function in a rat model of CKD-associated cachexia. HIIT with ES may lead to an innovative therapeutic intervention that can be utilized for patients with CKD-associated cachexia who have difficulty with full-body exercise.