Neuromuscular electrical stimulation in physical inactivity

Physical inactivity and immobilization have emerged as major health issues. Neuromuscular electrical stimulation (NMES) is a potential treatment to prevent the negative effects of physical inactivity, such as muscle atrophy and poor venous circulation. However, current NMES application is limited by poor compliance. Thus, the overarching aim of this thesis was to improve the efficacy of NMES targeting compliance by developing wearable NMES-pants. Development and testing of the NMES-pants on healthy, voluntary participants explored the effects on comfort, global muscle mRNA-expression, venous hemodynamics and blood coagulation.

To optimize electrode dimensions and positioning within the NMES-pants, the intensity (mA) needed for a visible muscle contraction (ML I) and comfort during NMES when applied with different electrode sizes and placements on the quadriceps (Q), hamstrings (H), and gluteus (G) muscles were tested. The NMES-pants were then created based on the combination of electrode size and placement that provided the best comfort and that required the lowest current intensity for ML I.

Subsequently, the textile electrodes in the NMES-pants were compared to commercial self-adhesive electrodes, by investigating the knee extensor force production created with NMES measured in an isokinetic dynamometer. We demonstrated that a contraction at 20% of the participant’s maximal voluntary contraction (MVC) could be reached at an acceptable level of discomfort with both methods. A large inter-individual variation in regards of comfort, intensity required, and force production was demonstrated, highlighting the importance of individually adjusted NMES for optimal compliance.

To further investigate the NMES-pants, the effects of Q-NMES on muscle activation were assessed by examining vastus lateralis muscle gene expression using RNA-sequencing before and three hours after a 30-minute Q-NMES-pants session and/or regular exercise. The NMES-intensity was set to 20% of each participant’s MVC and the EX-protocol was performed at 80% of 1-repetition-maximum. NMES induced 4448 differentially expressed genes (DEGs) with an 80%-overlap of the 2571 DEGs observed with EX. Genes well-known to be upregulated by EX were also upregulated by NMES to a lesser extent. Gene set enrichment analysis demonstrated many common pathways affected by both NMES and EX, but also some pathways exclusive to NMES, such as connective tissue proliferation.

Next, the effects of NMES-pants on venous hemodynamics and coagulation were explored. The peak venous velocity (PVV) in the femoral vein was assessed at ML I, and with an additional increase of six NMES-levels (ML II). NMES-pants significantly increased PVV from baseline by 93% at ML I and 173% at ML II. Additionally, levels of different coagulation factors and inflammatory markers were assessed with blood samples before and immediately after a 2-hour QHG-NMES-pants session. The NMES resulted in a small but significant increase in overall hemostatic potential, fibrinogen, and factor VIII, as well as a decrease in overall fibrinolytic potential. Furthermore, proteins which regulate inflammation and extracellular matrix degradation were differentially expressed by NMES.

The present findings of this thesis demonstrate that NMES-pants can be used, with single or combined thigh-gluteal muscle-stimulation, with a high comfort at low-intensity and with an acceptable discomfort at submaximal intensity. Treatment with NMES-pants produced intensity-dependent increases in venous hemodynamics and induced more DEGs, but with a significant overlap, as compared to exercise. These findings suggest that NMES can induce exercise-like molecular effects, with potential health and performance benefits in individuals unable to perform resistance exercise and that textile-based NMES-wearables have the potential to improve compliance with treatment.

List of scientific papers

I. Flodin J, Juthberg R, Ackermann PW. Effects of electrode size and placement on comfort and efficiency during low-intensity neuromuscular electrical stimulation of quadriceps, hamstrings and gluteal muscles. BMC Sports Sci Med Rehabil. 2022 Jan 16;14(1):11.
https://doi.org/10.1186/s13102-022-00403-7

II. Flodin J, Mikkelsen C, Ackermann PW. Knee extensor force production and discomfort during neuromuscular electrical stimulation of quadriceps with and without gluteal muscle co-stimulation. Eur J Appl Physiol. 2022 Jun;122(6):15211530.
https://doi.org/10.1007/s00421-022-04949-9

III. Flodin J, Wallenius P, Guo L, Persson NK, Ackermann P. Wearable Neuromuscular Electrical Stimulation on Quadriceps Muscle Can Increase Venous Flow. Ann Biomed Eng. 2023 Aug 19.
https://doi.org/10.1007/s10439-023-03349-0

IV. Flodin J, Reitzner SM, Emanuelsson EB, Sundberg CJ, Ackermann P. The effect of neuromuscular electrical stimulation on the human skeletal muscle transcriptome. Acta Physiol. 2024 Mar 8 240:e14129.
https://doi.org/10.1111/apha.14129

V. Flodin J, Reitzner SM, Mahmoud Hourani Soutari N, Ahmed AS, Guo L, Persson NK, Antovic JP, Ackermann PW. The effect of Neuromuscular Electrical Stimulation on Overall Hemostatic Potential and Coagulation Factors. [Manuscript]