Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Enhances the Collateral Blood Flow in the Ischemic Hindlimb

Yasukatsu Izumi*, Yasukatsu Izumi*, Takehiro Yamaguchi, Takanori Yamazaki, Naoto Yamashita, Yasuhiro Nakamura, Yasuhiro Nakamura, Masayuki Shiota, Masako Tanaka, Masako Tanaka, Soichi Sano, Mayuko Osada-oka, Mayuko Osada-oka, Kenei Shimada, Hideki Wanibuchi, Katsuyuki Miura, Minoru Yoshiyama, Hiroshi Iwao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Aim: 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. Conclusion: Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis.

Original languageEnglish
Pages (from-to)38-51
Number of pages14
JournalJournal of Atherosclerosis and Thrombosis
Issue number1
Publication statusPublished - 2015
Externally publishedYes


  • Angiogenesis
  • Carbon dioxide mist
  • Ischemia
  • Mass spectrometry
  • Peripheral arterial disease

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical


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