title: Percutaneous carbon dioxide treatment using a gas mist generator enhances the collateral blood flow in the ischemic hindlimb.
abstract: OBJECTIVE
  Highly concentrated carbon dioxide (CO2) is thought to be useful for ischemic diseases. We investigated whether treatment with a few micrometers of CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic effect in a mouse ischemic hindlimb model.
  
  
  METHODS
  Mice with unilateral hindlimb ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups. The lower body of the mice was encased in a polyethylene bag filled with each gaseous agent using a gas mist generator for 10 minutes daily.
  
  
  RESULTS
  According to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently higher after the seventh day of induction of ischemia in the CM group than in the UT group. The capillary density was also greater in the CM group on day 28 compared with that observed in the UT group. In addition, the parameters in the AM and CG groups were similar to those obtained in the UT group. The observed effects were abolished by the administration of an inhibitor of nitric oxide synthase (NOS). The vascular endothelial growth factor mRNA expression and protein levels and the phosphorylated endothelial NOS level were increased in the CM group compared with that observed in the UT group. A proteomic analysis using liquid chromatography-tandem mass spectrometry identified novel protein candidates regulated by CO2 mist.
  
  
  CONCLUSIONS
  Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis.
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan; Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamashita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.forename: Masako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Soichi
authors.initials: S
authors.lastname: Sano
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D010766:Phosphorylation; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology*; D014664:Vasodilation
chemical_list: D002245:Carbon Dioxide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse