Percutaneous Carbon Dioxide Treatment using a Gas Mist Generator Enhances the Collateral Blood Flow in the Ischemic Hindlimb
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概要
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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.
著者
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Sano Soichi
Department of Internal Medicine, Osaka City General Hospital
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Shimada Kenei
Department Of Cardiology Osaka City General Hospital
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SHIOTA Masayuki
Department of Pharmacology, Osaka City University Medical School
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Miura Katsuyuki
Applied Pharmacology And Therapeutics Osaka City Univ. Medical School Jpn
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Shiota Masayuki
Department Of Pharmacology Osaka City University Medical School
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Yamazaki Takanori
Department Of Biomolecular Engineering Tokyo Institute Of Technology
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Izumi Yasukatsu
Department Of Pharmacology Osaka City University Graduate School Of Medicine
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Tanaka Masako
Department Of Applied Physics Osaka City University:(present Address) Department Of Physics Tohoku U
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Yamashita Naoto
Department Of Internal Medicine Shobara Red Cross Hospital
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Nakamura Yasuhiro
Department Cardiology Baba Memorial Hospital
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Iwao Hiroshi
Department Of Cardiovascular Medicine Akita University Graduate School Of Medicine
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Wanibuchi Hideki
Department Of Pathology Osaka City University Graduate School Of Medicine
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Osada-Oka Mayuko
Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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Yamaguchi Takehiro
Department of Internal Medicine and Cardiology, Matsue Seikyo Hospital
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YOSHIYAMA Minoru
Department Internal Medicine and Cardiology, Osaka City University School of Medicine
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Shimada Kenei
Department of Cardiovascular Medicine, Osaka City University Medical School
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