Low force exercise training using muscle stimulation adapts physiologic phenotype in people with Spinal Cord Injury

Abstract

Physical activity, even in short bursts, is critical to maintain human skeletal muscle. Low physical activity levels are associated with poor health, chronic non‐communicable diseases (NCDs), and impaired cognition in people with intact nervous systems as they age. Exercise as a form of medicine increases physical activity levels, attenuates the development of NCDs, and improves cognitive capacity. Because people with spinal cord injury (SCI) cannot volitionally activate their paralyzed muscles, the musculoskeletal system deteriorates with an increased risk for NCDs and cognitive decline as they age. High force electrically induced exercise is risky; therefore, a safe low‐force alternative is needed. Whether training using a low‐force electrically induced exercise can influence muscle and systemic health markers in people with SCI is unknown.PurposeTo determine if low‐force electrically induced exercise changes the phenotype and metabolic health of paralyzed skeletal muscle in people with SCI.Methods10 people with complete SCI completed electrically induced exercise training using low‐force (3Hz) stimulation of the quadriceps. Participants targeted at least 5 exercise training sessions per week. A muscle fatigue test and fasting venous blood draw, measuring CRP, insulin, leptin, BDNF, myostatin, and PTH, were performed before and after training. Muscle biopsies were obtained from a trained and untrained vastus lateralis. Gene expression was measured using the Affymetrix HTA 2.0 array from the trained and untrained muscle samples. All participants provided written consent approved by the University of Iowa Institutional Review Board in compliance with the Declaration of Helsinki.ResultsParticipants were compliant completing ~119±19% of the training sessions for ~7.2±1.2 months. There was a ~68% improvement in fatigue after of exercise training compared to baseline (p=0.002). There was a significant increase in the resting gene expression of slow‐twitch proteins MYH6(p=0.023), MYH7(p=0.034), and MYL3(p=0.022) compared to the untrained limb. Serum concentration of CRP, insulin, myostatin, and leptin were decreased by ~74% (p=0.089), ~179%(0.057), ~64%(p=0.096), and ~79%(p=0.021) after exercise training compared to baseline, respectively. Serum BDNF and PTH concentration were increased by ~70%(p=0.093) and ~78%(p=0.048) after exercise training, respectively.ConclusionsLow‐force electrically induced exercise training improved fatigability and phenotype of paralyzed muscle. Consistent with this change, the homeostatic gene expression of slow‐twitch proteins (MYH6, MYH7, and MYL3) were increased, but the transcription factors (PGC1a and MSTN) remained unchanged. Serum biomarkers (CRP, insulin, leptin, BDNF, myostatin and PTH) showed a consistent trend systemic metabolic health after training. Together, this study highlights the potential of low‐force electrically induced exercise to improve the health in people with chronic SCI, though the minimum duration of training required may be delayed compared to other exercises modalities.Support or Funding InformationResearch SupportThis study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109