The Journal of Physiological Sciences

, Volume 69, Issue 6, pp 885–893 | Cite as

Neuromuscular stimulation ameliorates ischemia-induced walking impairment in the rat claudication model

  • Momoko Shiragaki-OgitaniEmail author
  • Keita Kono
  • Futoshi Nara
  • Atsushi Aoyagi
Original Paper


Intermittent claudication (IC) is the most common symptom of peripheral arterial disease which significantly deteriorates the quality of life of patients. Exercise training is by far the most effective treatment for IC; however, the underlying mechanisms remain elusive. To determine the local mechanisms by which exercise training improves walking performance in claudicants, we developed an implantable device to locally induce ischemic skeletal muscle contraction mimicking exercise via electrical stimulation (ES). Rats were assigned to four groups, Sham, Ischemia (Isch), Isch + exercise and Isch + ES groups. Following both unilateral femoral and iliac artery occlusion, rats showed sustained impairment of walking performance in the treadmill test. Chronic low-frequency ES of ischemic skeletal muscles for 2 weeks significantly recovered the occlusion-induced walking impairment in the rat claudication model. We further analyzed the ischemic skeletal muscles immunohistochemically following ES or exercise training; both ES and exercise training significantly increased capillaries in the ischemic skeletal muscles and shifted the muscle fibers toward oxidative types. These findings demonstrate that ES takes on common features of exercise in the rat claudication model, which may facilitate investigations on the local mechanisms of exercise-induced functional recovery.


Intermittent claudication Exercise Electrical stimulation Skeletal muscle Mechanism 



The authors thank Jun Harada for the scientific counsel.

Author contributions

Momoko Shiragaki-Ogitani: conceptualization, formal analysis, investigation, and writing—original draft. Keita Kono: writing—original draft. Futhoshi Nara: conceptualization and writing—original draft. Atsushi Aoyagi: conceptualization, formal analysis, investigation, and writing—original draft.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Daiichi Sankyo Co., Ltd.

Supplementary material

12576_2019_701_MOESM1_ESM.pdf (217 kb)
Supplementary material 1 Muscle weight of tibialis anterior (TA) following IAO + 2FAO ischemia (Isch) and effects of exercise training (EX) and electrical stimulation (ES) in rats. Values are presented as the percentage to mean values of Sham group. n   = 5 rats per group. Values are presented as mean ± SE and statistical significance was determined using Dunnett’s test. *P < 0.05, **P < 0.01, vs. Sham group (PDF 217 kb)
12576_2019_701_MOESM2_ESM.docx (24 kb)
Supplementary material 2 (DOC 25 kb)


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Venture Science LaboratoriesDaiichi Sankyo Co., Ltd.TokyoJapan
  2. 2.Global Project Management DepartmentDaiichi Sankyo Co., Ltd.TokyoJapan
  3. 3.Ube Industries, Ltd. Pharmaceuticals Research LaboratoryUbeJapan

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