Pathology International 2004; 54: 740–741

Blackwell Science, LtdOxford, UKPINPathology International1320-54632004 Japanese Society of PathologySeptember 2004549740741Letter to the Editor

Letter to the Editor

To the Editor:Subsequent to the study by Ebina and colleagues1 evaluatingthe mechanism of electrical stimulation (ES) inducing thepromotion of capillary density in normal skeletal muscle, wepublished a study2 that evaluated ES in relation to arterio-genesis and angiogenesis. A rabbit model was used, in whichthe femoral arteries were excised unilaterally (Fig. 1) and ESwas applied to the left hind limb excision site for 30 contrac-tions per minute, at 3 V, and single impulses were appliedcontinuously, 24 h a day, for 1 month’s duration (Fig. 2).We found that ES opened pre-existing collaterals (arterio-genesis) to a greater extent (approximately 1.5 times controlvalues) than the body’s normal compensatory response toacute ischemia. In addition, ES promoted a dramatic three-fold increase in capillary density (angiogenesis) in contrastto the body’s normal response, in which capillary densitydecreased by 50%. Angiography further revealed that thenew vessels restored distal blood flow by arising proximaland distal to the site of excision and then connecting witheach other. Our study’s macroscopic findings supplementand support Ebina et al.’s microscopic findings in that ES is

a powerful tool that promotes the opening/production of bloodvessels and increases blood flow in muscle tissue.

Imran SheikhRajesh MaddikuntaValeri S. ChekanovAurora Sinai/St Luke’s Medical CentersUniversity of Wisconsin Medical School – MilwaukeeClinical CampusMilwaukeeWisconsin, USA

REFERENCES

1 Ebina T, Hoshi N, Kobayashi M et al. Physiological angiogen-esis in electrically stimulated skeletal muscle in rabbits:Characterization of capillary sprouting by ultrastructural 3-Dreconstruction study. Pathol Int 2002; 52: 702–12.

2 Chekanov V, Rayel R, Krum D et al. Electrical stimulationpromotes angiogenesis in a rabbit hind-limb ischemia model.Vasc Endovascular Surg 2002; 36: 357–66.

Figure 1 Angiogram immediately after femoral artery excision.Figure 2 Angiogram at 1 month after femoral artery excision andafter 1 month of electrical stimulation.

741September 2004549Letter to the Editor

Author’s Reply:We believe that our report1 strongly supports Imran Sheikhet al.’s findings.2 Their findings in particular predict thatarterial restructuring by electrical stimulation (ES), via anincrease in blood flow, is consistent with an increase in cap-illary density. Recently, we found that a high flow inducedremarkable endothelial proliferation in the carotid artery ofrabbits and was compatible with capillary angiogenesis.3,4

Therefore, when we can induce capillary angiogenesis, arte-rial restructuring can also be induced simultaneously. Weconsider that ES, via an increase in blood flow, shall be veryeffective.

Hirotake MasudaToshihiro EbinaDivision of Organ and Cellular PathologyDepartment of Pathology and ImmunologyAkita University School of MedicineAkita, Japan

REFERENCES

1 Ebina T, Hoshi N, Kobayashi M et al. Physiological angiogen-esis in electrically stimulated skeletal muscle in rabbits:Characterization of capillary sprouting by ultrastructural 3-Dreconstruction study. Pathol Int 2002; 52: 702–12.

2 Chekanov V, Rayel R, Krum D et al. Electrical stimulationpromotes angiogenesis in a rabbit hind-limb ischemia model.Vasc Endovascular Surg 2002; 36: 357–66.

3 Masuda H, Kawamura K, Nanjo H et al. Ultrastructure of endo-thelial cells under flow alteration. Microsc Res Tech 2003; 60:2–12.

4 Sho E, Komatsu M, Sho M et al. High flow drives vascularendothelial cell proliferation during flow-induced arterial remod-eling associated with the expression of vascular endothelialgrowth factor. Exp Mol Pathol 2003; 75: 1–11.