title: Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb.
abstract: OBJECTIVE
  Whole-body periodic acceleration (WBPA) has been developed as a passive exercise technique to improve endothelial function by increasing shear stress through repetitive movements in spinal axis direction. We investigated the effects of WBPA on blood flow recovery in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease.
  
  
  RESULTS
  After unilateral femoral artery excision, mice were assigned to either the WBPA (n=15) or the control (n=13) group. WBPA was applied at 150 cpm for 45 minutes under anesthesia once a day. WBPA significantly increased blood flow recovery after ischemic surgery, as determined by laser Doppler perfusion imaging. Sections of ischemic adductor muscle stained with anti-CD31 antibody showed a significant increase in capillary density in WBPA mice compared with control mice. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in skeletal muscle. The proangiogenic effect of WBPA on ischemic limb was blunted in eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on revascularization are eNOS dependent. Quantitative real-time polymerase chain reaction analysis showed significant increases in angiogenic growth factor expression in ischemic hindlimb by WBPA. Facilitated blood flow recovery was observed in a mouse model of diabetes despite there being no changes in glucose tolerance and insulin sensitivity. Furthermore, both a single session and 7-day repeated sessions of WBPA significantly improved blood flow in the lower extremity of patients with peripheral arterial disease.
  
  
  CONCLUSIONS
  WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of proangiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable noninvasive intervention to facilitate therapeutic angiogenesis.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Rokutanda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Miura
authors.forename: Shota
authors.initials: S
authors.lastname: Fukuda
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Araki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hanatani
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Taishi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kataoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshikawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000054:Acceleration; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005500:Follow-Up Studies; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015915:Motion Therapy, Continuous Passive / Q000379:methods*; D018482:Muscle, Skeletal / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000503:physiopathology / Q000628:therapy*; D010805:Physical Conditioning, Animal / Q000379:methods*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D052250:Nitric Oxide Synthase Type III