Electrical Impedance Myography to Detect the Effects of Electrical Muscle Stimulation in Wild Type and Mdx Mice

Abstract

ObjectiveTools to better evaluate the impact of therapy on nerve and muscle disease are needed. Electrical impedance myography (EIM) is sensitive to neuromuscular disease progression as well as to therapeutic interventions including myostatin inhibition and antisense oligonucleotide-based treatments. Whether the technique identifies the impact of electrical muscle stimulation (EMS) is unknown.MethodsTen wild-type (wt) C57B6 mice and 10 dystrophin-deficient (mdx) mice underwent 2 weeks of 20 min/day EMS on left gastrocnemius and sham stimulation on the right gastrocnemius. Multifrequency EIM data and limb girth were obtained before and at the conclusion of the protocol. Muscle weight, in situ force measurements, and muscle fiber histology were also assessed at the conclusion of the study.ResultsAt the time of sacrifice, muscle weight was greater on the EMS-treated side than on the sham-stimulated side (p = 0.018 for wt and p = 0.007 for mdx). Similarly, in wt animals, EIM parameters changed significantly compared to baseline (resistance (p = 0.009), reactance (p = 0.0003) and phase (p = 0.002); these changes were due in part to reductions in the EIM values on the EMS-treated side and elevations on the sham-simulated side. Mdx animals showed analogous but non-significant changes (p = 0.083, p = 0.064, and p = 0.57 for resistance, reactance and phase, respectively). Maximal isometric force trended higher on the stimulated side in wt animals only (p = 0.06). Myofiber sizes in wt animals were also larger on the stimulated side than on the sham-stimulated side (p = 0.034); no significant difference was found in the mdx mice (p = 0.79).ConclusionEIM is sensitive to stimulation-induced muscle alterations in wt animals; similar trends are also present in mdx mice. The mechanisms by which these EIM changes develop, however, remains uncertain. Possible explanations include longer-term trophic effects and shorter-term osmotic effects.

Non‐invasive assessment of muscle injury in healthy and dystrophic animals with electrical impedance myography

“…We measured left and right longitudinal quadriceps impedance between 10 kH z and 1 MH z (EIM1103, Skulpt, Inc., San Francisco, California) using a surface electrode array described elsewhere (Fig. B) . Data were collected after the fur was clipped and all remaining fur was removed using a depilatory agent.…”

“…EIM works on the premise that these properties are altered in disease, and earlier work has demonstrated differences in the electrical material properties of healthy muscle compared with diseased muscles. To date, EIM has proven a valuable tool for detecting a variety of neuromuscular diseases both in humans and in animal models . EIM has also been shown to be sensitive to the effects of therapy in spinal muscular atrophy and recovery from disuse .…”

Frequency-Dependent Reaction of the Triceps Surae Muscle of the Mouse During Electromyostimulation

“…The depletion of the Na + (or the accumulation of K + ) could reduce the muscle membrane excitability sufficiently to explain the force loss during a higher frequency (Moritani et al, 1985). Frontiers in Physiology | www.frontiersin.org Due to different stimulation protocols and other environmental conditions, the comparison of the results presented here to other animal studies remains complicated (Guo et al, 2012;Kobayashi et al, 2012;Tsutaki et al, 2013;Hering et al, 2016;Li et al, 2016;Valenzuela et al, 2017). Nevertheless, similar results could be observed in the behavior of the muscle during stimulation with different frequencies, even if the environmental influences and the way of stimulation of the muscle (ex vivo, needle electrode) were different.…”

Estimating myofiber cross‐sectional area and connective tissue deposition with electrical impedance myography: A study in D2‐mdx mice

“…23 Indeed, our previous EIM studies were all based on this model. 25,[46][47][48] However, muscle pathology in these animals is far less severe than in DMD patients. Therefore, we chose to use the D2-mdx mouse model of DMD in the current study.…”