2025/03/27 更新

写真a

イズタニ ヒロノリ
泉谷 裕則
Izutani Hironori
所属
大学院医学系研究科 医学専攻 教授
職名
教授
連絡先
メールアドレス
外部リンク

学位

  • 博士(医学) ( 大阪大学 )

研究分野

  • ライフサイエンス / 心臓血管外科学

論文

  • 張力固定型チタンケーブルとメッシュプレートを併用した胸骨固定法の検討

    檜垣 知秀, 黒部 裕嗣, 福西 琢真, 坂上 倫久, 西村 隆, 泉谷 裕則

    日本心臓血管外科学会雑誌   53 ( 2 )   56 - 61   2024年3月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本心臓血管外科学会  

    [背景と目的]胸骨正中切開後の不安定な胸骨固定は,感染症・出血のリスク増加や胸骨動揺に伴う疼痛等によるリハビリテーションの遅れなど,術後の経過に影響を与える要因の1つとしてあげられる.従来のワイヤー固定法では,経験年数にも左右されるが,閉胸時の胸骨離断やワイヤーの不完全固定など懸念としてあげられてきた.一方で,近年使用されてきた体内固定用胸骨プレートはその患者適応に制限があり,全例で使うことはむずかしい.今回,より安定した胸骨固定を目的に,チタンケーブルとメッシュプレートを併用した新固定法(N群)の手技を検討し,従来のワイヤーのみを用いた胸骨固定法(O群)と比較検討した.[方法・結果]2020年8月~2023年4月に施行した成人開心術のうち,術後CTを撮影した155例を対象とし,N群(86例:M 65,F 21),O群(69例:M 50,F 19)に分類した.術前因子としては,術時年齢(N群:O群=68.4±10.6 : 69.6±11.5歳(<i>p</i>=0.25)),BMI(N群:O群=23.0±3.7 : 24.1±7.7(<i>p</i>=0.16)),HbA1c(N群:O群=6.3±1.1:8.0±10.3 %(<i>p</i>=0.10))であり,両群間で有意差はなかった.術後CT解析では,第3肋骨位での術後の胸骨のずれを測定した.横ずれ(N群:O群=0.22±0.73:0.83±1.08 mm(<i>p</i>=0.005))は有意に減少し,縦ずれ(N群:O群=0.53±0.86:0.72±1.14 mm(<i>p</i>=0.13))は統計学的有意差を認めないものの減少傾向を認めた.[結語]チタンケーブルとメッシュプレートを併用した閉胸法は,術後の胸骨ずれを減少させ,その結果,安定した胸骨固定に寄与すると考えられる.チタンケーブルの固定手技は,テンショナーを用いた一定力で胸骨固定できる一方で,胸骨カッティングの懸念を指摘されていた.そのためメッシュプレートを胸骨背面に挿入して固定することにより,胸骨カッティングを防止し,より安定した胸骨固定に繋がると考えられた.

    DOI: 10.4326/jjcvs.53.56

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    その他リンク: https://search.jamas.or.jp/link/ui/2024187899

  • 張力固定型チタンケーブルとメッシュプレートを併用した胸骨固定法の検討

    檜垣 知秀, 黒部 裕嗣, 福西 琢真, 坂上 倫久, 西村 隆, 泉谷 裕則

    日本心臓血管外科学会雑誌   53 ( 2 )   56 - 61   2024年3月

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    記述言語:日本語   出版者・発行元:(NPO)日本心臓血管外科学会  

    [背景と目的]胸骨正中切開後の不安定な胸骨固定は,感染症・出血のリスク増加や胸骨動揺に伴う疼痛等によるリハビリテーションの遅れなど,術後の経過に影響を与える要因の1つとしてあげられる.従来のワイヤー固定法では,経験年数にも左右されるが,閉胸時の胸骨離断やワイヤーの不完全固定など懸念としてあげられてきた.一方で,近年使用されてきた体内固定用胸骨プレートはその患者適応に制限があり,全例で使うことはむずかしい.今回,より安定した胸骨固定を目的に,チタンケーブルとメッシュプレートを併用した新固定法(N群)の手技を検討し,従来のワイヤーのみを用いた胸骨固定法(O群)と比較検討した.[方法・結果]2020年8月~2023年4月に施行した成人開心術のうち,術後CTを撮影した155例を対象とし,N群(86例:M65,F21),O群(69例:M50,F19)に分類した.術前因子としては,術時年齢(N群:O群=68.4±10.6:69.6±11.5歳(p=0.25)),BMI(N群:O群=23.0±3.7:24.1±7.7(p=0.16)),HbA1c(N群:O群=6.3±1.1:8.0±10.3%(p=0.10))であり,両群間で有意差はなかった.術後CT解析では,第3肋骨位での術後の胸骨のずれを測定した.横ずれ(N群:O群=0.22±0.73:0.83±1.08mm(p=0.005))は有意に減少し,縦ずれ(N群:O群=0.53±0.86:0.72±1.14mm(p=0.13))は統計学的有意差を認めないものの減少傾向を認めた.[結語]チタンケーブルとメッシュプレートを併用した閉胸法は,術後の胸骨ずれを減少させ,その結果,安定した胸骨固定に寄与すると考えられる.チタンケーブルの固定手技は,テンショナーを用いた一定力で胸骨固定できる一方で,胸骨カッティングの懸念を指摘されていた.そのためメッシュプレートを胸骨背面に挿入して固定することにより,胸骨カッティングを防止し,より安定した胸骨固定に繋がると考えられた.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01122&link_issn=&doc_id=20240401280002&doc_link_id=10.4326%2Fjjcvs.53.56&url=https%3A%2F%2Fdoi.org%2F10.4326%2Fjjcvs.53.56&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Reply: Low-Grade Inflammation: A Familiar Factor in Cardiovascular Diseases. 国際誌

    Tomohisa Sakaue, Hironori Izutani

    JACC. Basic to translational science   8 ( 11 )   1476 - 1476   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jacbts.2023.09.009

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  • 胸部大動脈瘤に対するステントグラフト内挿術後のtype IIエンドリークに対して瘤内直接穿刺による塞栓が有効であった1例

    福西 琢真, 田中 宏明, 本郷 哲央, 八杉 巧, 黒部 裕嗣, 西村 隆, 薦田 宗則, 檜垣 知秀, 坂上 倫久, 泉谷 裕則

    血管外科   42 ( 1 )   82 - 87   2023年11月

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    記述言語:日本語   出版者・発行元:血管外科症例検討会  

    症例は40歳代の女性。全身性エリテマトーデスによる慢性腎不全で生体腎移植を受けている。経過中に拡大する57mm大の紡錘状下行大動脈瘤を認め、zone3/4に対して胸部ステントグラフト内挿術(TEVAR)を施行した。術後2年でのCT検査で62mmと再度瘤拡大を認め、血管造影を行い下甲状腺動脈等からの側副路を介して気管支動脈から瘤内に血流を認めるtype IIのエンドリーク(EL)と診断した。側副路からのカテーテル挿入は困難と判断し、CTガイド下瘤内直接穿刺で気管支動脈と肋間動脈の選択的にコイル塞栓を行い、さらに瘤内をn-butyl-cyanoacryrate:NBCA、リピオドール、エタノール混合液にて充填した。術後半年のCTでは、瘤径拡大なく経過良好である。(著者抄録)

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  • 生体分解性素材を用いた医療デバイスの開発

    黒部 裕嗣, 新岡 俊治, 平田 陽一郎, 福西 琢真, 森谷 友造, 倉田 美恵, 坂上 倫久, 檜垣 高史, 泉谷 裕則

    愛媛医学   42 ( 3 )   119 - 126   2023年9月

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    記述言語:日本語   出版者・発行元:愛媛医学会  

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  • Bioprosthetic Valve Deterioration: Accumulation of Circulating Proteins and Macrophages in the Valve Interstitium. 国際誌

    Tomohisa Sakaue, Tadaaki Koyama, Yoshitsugu Nakamura, Keitaro Okamoto, Takayuki Kawashima, Tadashi Umeno, Yasuhide Nakayama, Shinji Miyamoto, Fumiaki Shikata, Mika Hamaguchi, Jun Aono, Mie Kurata, Kenji Namiguchi, Shunji Uchita, Junya Masumoto, Osamu Yamaguchi, Shigeki Higashiyama, Hironori Izutani

    JACC. Basic to translational science   8 ( 7 )   862 - 880   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Histologic evaluations revealed excessive accumulations of macrophages and absence of fibroblastic interstitial cells in explanted bioprosthetic valves. Comprehensive gene and protein expression analysis and histology unveiled an accumulation of fibrinogen and plasminogen, an activator of infiltrated macrophages, from degenerated valve surfaces in the interstitial spaces. These pathologies were completely reproduced in a goat model replaced with an autologous pericardium-derived aortic valve. Further preclinical animal experiments using goats demonstrated that preventing infiltration of macrophages and circulating proteins by increasing collagen density and leaflet strength is an effective treatment option.

    DOI: 10.1016/j.jacbts.2023.01.003

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  • 循環補助用心内留置型ポンプカテーテルImpella挿入後の大動脈弁尖の病理学的検討

    倉田 美恵, 三好 徹, 東 晴彦, 坂上 倫久, 井上 勝次, 西村 隆, 池田 俊太郎, 泉谷 裕則, 山口 修, 増本 純也

    脈管学   63 ( 1 )   12 - 12   2023年2月

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    記述言語:日本語   出版者・発行元:(一社)日本脈管学会  

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  • 安全に小開胸心臓手術を遂行するために 下肢灌流を考慮したSize Down送血管使用時のパラメーターの検討

    黒部 裕嗣, 泉谷 裕則, 檜垣 知秀, 福西 琢真, 管野 司, 三木 航太, 伴野 誠幸, 杉村 直紀, 平川 太基, 塚本 伶央奈, 品部 雅俊, 坂上 倫久, 山田 文哉, 西村 隆, 八杉 巧

    日本胸部外科学会定期学術集会   75回   CP5 - 5   2022年10月

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    記述言語:日本語   出版者・発行元:(一社)日本胸部外科学会  

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  • 大動脈弁石灰化におけるプロスタグランジン代謝経路の役割

    坂上 倫久, 濱口 美香, 青野 潤, 薦田 宗則, 福西 琢真, 黒部 裕嗣, 西村 隆, 泉谷 裕則

    日本胸部外科学会定期学術集会   75回   JP2 - 3   2022年10月

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    記述言語:日本語   出版者・発行元:(一社)日本胸部外科学会  

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  • 心拍動下MICS弁形成術の工夫

    檜垣 知秀, 黒部 裕嗣, 薦田 宗則, 福西 琢真, 坂上 倫久, 西村 隆, 八杉 巧, 泉谷 裕則

    小切開・鏡視外科学会雑誌   13 ( 1 )   47 - 47   2022年6月

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    記述言語:日本語   出版者・発行元:(NPO)小切開・鏡視外科学会  

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  • Huge Right Coronary Artery Aneurysm in Mixed Connective Tissue Disease.

    Haruhiko Higashi, Chiharuko Iio, Shuntaro Ikeda, Teruyoshi Uetani, Shinji Inaba, Katsuji Inoue, Tomohisa Sakaue, Hironori Izutani, Osamu Yamaguchi

    Circulation journal : official journal of the Japanese Circulation Society   86 ( 5 )   881 - 881   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1253/circj.CJ-21-1001

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  • Hypoxic Culture Maintains Cell Growth of the Primary Human Valve Interstitial Cells with Stemness. 査読 国際誌

    Kaho Kanno, Tomohisa Sakaue, Mika Hamaguchi, Kenji Namiguchi, Daisuke Nanba, Jun Aono, Mie Kurata, Junya Masumoto, Shigeki Higashiyama, Hironori Izutani

    International journal of molecular sciences   22 ( 19 )   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro.

    DOI: 10.3390/ijms221910534

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  • Pathological Evidence of Native Aortic Valve Injury After Impella Support. 国際誌

    Haruhiko Higashi, Takashi Nishimura, Jun Aono, Tomohisa Sakaue, Mie Kurata, Hironori Izutani, Osamu Yamaguchi

    Circulation. Heart failure   14 ( 2 )   e007571   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1161/CIRCHEARTFAILURE.120.007571

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  • Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation. 国際誌

    Kenji Namiguchi, Tomohisa Sakaue, Mikio Okazaki, Kaho Kanno, Yuhei Komoda, Fumiaki Shikata, Mie Kurata, Noritaka Ota, Yoshiaki Kubota, Hirotsugu Kurobe, Takashi Nishimura, Junya Masumoto, Shigeki Higashiyama, Hironori Izutani

    Frontiers in cardiovascular medicine   8   761591 - 761591   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objectives: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. Methods and Results: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. Conclusions: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.

    DOI: 10.3389/fcvm.2021.761591

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  • Usefulness of contrast computed tomography for diagnosing left ventricular thrombus before impella insertion. 査読

    Yasuhisa Nakao, Jun Aono, Kenji Namiguchi, Takashi Nishimura, Hironori Izutani, Haruhiko Higashi, Shinji Inaba, Kazuhisa Nishimura, Katsuji Inoue, Shuntaro Ikeda, Osamu Yamaguchi

    Journal of cardiology cases   22 ( 6 )   291 - 293   2020年12月

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    記述言語:英語  

    The Impella (Abiomed, Danvers, MA, USA) is a novel percutaneous heart pump device for left ventricular (LV) assistance; however, LV thrombus is a notable contraindication for this device. Contrast computed tomography assessment is useful for detecting LV thrombus and preventing thromboembolism in patients recommended for Impella use. <Learning objective: The Impella (Abiomed, Danvers, MA, USA) is a heart pump device which aspirates blood from a left ventricular (LV) cavity and ejects it into an ascending aorta. Therefore, LV thrombus should be explored before the Impella insertion to prevent systemic embolism. Generally, echocardiography is the first choice to detect LV thrombus. Given limited diagnostic sensitivity for detecting LV thrombus in echocardiography, contrast computed tomography might be a useful strategy for the patient targeting Impella insertion.>.

    DOI: 10.1016/j.jccase.2020.07.016

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  • A case report of thrombotic complete obstruction of the ascending aorta as a complication of Venoarterial extracorporeal membrane oxygenation support: Steps to prevent thrombosis

    Tasuku Nishihara, Natsuko Kudamatsu, Taisuke Hamada, Yukihiro Nakata, Waichi Yamamoto, Hideyuki Nandate, Kenji Namiguchi, Takashi Nishimura, Hironori Izutani, Toshihiro Yorozuya

    Journal of Cardiothoracic Surgery   15 ( 1 )   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central  

    Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis. Case presentation: A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated
    therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation. Conclusions: To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.

    DOI: 10.1186/s13019-020-01239-3

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  • Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves

    Tomohisa Sakaue, Mika Hamaguchi, Jun Aono, Koh-ichi Nakashiro, Fumiaki Shikata, Natsuki Kawakami, Yusuke Oshima, Mie Kurata, Daisuke Nanba, Junya Masumoto, Osamu Yamaguchi, Shigeki Higashiyama, Hironori Izutani

    ANNALS OF THORACIC SURGERY   110 ( 1 )   40 - 49   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Background. The molecular mechanisms underlying aortic valve calcification are poorly understood. Here, we aimed to identify the master regulators of calcification by comparison of genes in valve interstitial cells (VICs) with calcified and noncalcified aortic valves.Methods. Calcified aortic valves were surgically excised from patients with aortic valve stenosis who required aortic valve replacements. Noncalcified and calcified sections were obtained from aortic valve leaflets. Collagenase-digested tissues were seeded into dishes, and VICs adhering to the dishes were cultured for 3 weeks, followed by comprehensive gene expression analysis. Functional analyses of identified proteins were performed by in vitro calcification assays. Tissue localization was determined by immunohistochemical staining for normal (n = 11) and stenotic valves (n = 30).Results. We found 87 genes showing greater than a twofold change in calcified tissues. Among these genes, 68 were downregulated and 19 were upregulated. Cyclooxygenase-1 (COX1) messenger RNA and protein levels were upregulated in VICs from calcified tissues. The COX1 messenger RNA and protein levels in VICs were also strongly increased by stimulation with osteoblast differentiation medium. These were VIC-specific phenotypes and were not observed in other cell types. Immunohistochemical staining revealed that COX1-positive VICs were specifically localized in the calcified area of aortic valve tissues.Conclusions. The VIC-specific COX1 overexpression played a crucial role in calcification by promoting osteoblast differentiation in aortic valve tissues. (Ann Thorac Surg 2020;110:40-9) (C) 2020 by The Society of Thoracic Surgeons

    DOI: 10.1016/j.athoracsur.2019.09.085

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  • A simple mouse model of pericardial adhesions. 査読 国際誌

    Ai Kojima, Tomohisa Sakaue, Mikio Okazaki, Fumiaki Shikata, Mie Kurata, Yuuki Imai, Hirotomo Nakaoka, Junya Masumoto, Shunji Uchita, Hironori Izutani

    Journal of cardiothoracic surgery   14 ( 1 )   124 - 124   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Postoperative pericardial adhesions are considered a risk factor for redo cardiac surgery. Several large- and medium-size animal models of pericardial adhesions have been reported, but small animal models for investigating the development of anti-adhesion materials and molecular mechanisms of this condition are lacking. In this study, we aimed to establish a simple mouse model of pericardial adhesions to address this gap. METHODS: We administered blood, minocycline, picibanil, and talc into the murine pericardial cavity via one-shot injection. Micro-computed tomography analyses of contrast agent-injected mice were carried out for methodological evaluation. We investigated various dosages and treatment durations for molecules identified to be inducers of pericardial adhesion. The adhesive grade was quantified by scoring the strength and volume of adhesion tissues at sacrificed time points. Histological staining with hematoxylin and eosin and Masson's trichrome, and immunostaining for F4/80 or αSMA was performed to investigate the structural features of pericardial adhesions, and pathological features of the pericardial adhesion tissue were compared with human clinical specimens. RESULTS: Administration of talc resulted in the most extensive pericardial adhesions. Micro-computed tomography imaging data confirmed that accurate injection into the pericardial cavity was achieved. We found the optimal condition for the formation of strong pericardial adhesions to be injection of 2.5 mg/g talc for 2 weeks. Furthermore, histological analysis showed that talc administration led to an invasion of myofibroblasts and macrophages in the pericardial cavity and epicardium, consistent with pathological findings in patients with left ventricular assistive devices. CONCLUSIONS: We successfully established a simple mouse model of talc-induced pericardial adhesions, which mimics human pathology and could contribute to solving the clinical issues related to pericardial adhesions.

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  • Impact of the sampling rate of dynamic myocardial computed tomography perfusion on the quantitative assessment of myocardial blood flow. 査読

    Yokoi T, Tanabe Y, Kido T, Kurata A, Kido T, Uetani T, Ikeda S, Izutani H, Miyagawa M, Mochizuki T

    Clinical imaging   56   93 - 101   2019年4月

  • Impella 5.0 Mechanical Assist Device Catheter-Induced Severe Hemolysis Due to Giant Swinging Motion - New Concern in Impella Usage. 査読

    Nakao Y, Aono J, Tasaka T, Uetani T, Higashi H, Ikeda S, Yorozuya T, Izutani H, Yamaguchi O

    Circulation journal : official journal of the Japanese Circulation Society   83 ( 10 )   2080   2019年3月

  • Biochemical and histological evidence of deteriorated bioprosthetic valve leaflets: the accumulation of fibrinogen and plasminogen. 査読

    Sakaue T, Nakaoka H, Shikata F, Aono J, Kurata M, Uetani T, Hamaguchi M, Kojima A, Uchita S, Yasugi T, Higashi H, Suzuki J, Ikeda S, Higaki J, Higashiyama S, Izutani H

    Biology open   7 ( 8 )   2018年8月

  • Refractory ventricular fibrillations after surgical repair of atrial septal defects in a patient with CACNA1C gene mutation - case report 査読

    Ai Kojima, Fumiaki Shikata, Toru Okamura, Takashi Higaki, Seiko Ohno, Minoru Horie, Shunji Uchita, Yujiro Kawanishi, Kenji Namiguchi, Takumi Yasugi, Hironori Izutani

    JOURNAL OF CARDIOTHORACIC SURGERY   12 ( 1 )   118   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history.
    Case presentation: A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8.
    Conclusions: This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

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  • Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation 査読

    Tomoki Sakaue, Jun Suzuki, Mika Hamaguchi, Chika Suehiro, Akiko Tanino, Tomoaki Nagao, Teruyoshi Uetani, Jun Aono, Hirotomo Nakaoka, Mie Kurata, Tomohisa Sakaue, Takafumi Okura, Takumi Yasugi, Hironori Izutani, Jitsuo Higaki, Shuntaro Ikeda

    HYPERTENSION   70 ( 4 )   780 - +   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Perivascular adipose tissue exhibits characteristics of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of obesity/metabolic syndrome. However, the precise role of perivascular adipose tissue in the progression of abdominal aortic aneurysm remains unclear. To test the hypothesis that genetic deletion of angiotensin II type 1a (AT(1a)) receptor in perivascular visceral adipose tissue (VAT) can attenuate aortic aneurysm formation in apolipoprotein E-deficient (ApoE(-/-)) mice, we performed adipose tissue transplantation experiments by using an angiotensin II-induced aneurysm murine model, in which we transplanted VAT from ApoE(-/-) or ApoE(-/-) AT(1a)(-/-) donor mice onto the abdominal aorta of ApoE(-/-) recipient mice. Compared with ApoE-/VAT transplantation, ApoE(-/-)AT(1a)(-/-) VAT transplantation markedly attenuated aortic aneurysm formation, macrophage infiltration, and gelatinolytic activity in the abdominal aorta. AT(1a) receptor activation led to the polarization of macrophages in perivascular VAT toward the proinflammatory phenotype. Moreover, osteopontin expression and gelatinolytic activity were considerably lower in ApoE(-/-)AT(1a)(-/-) perivascular VAT than in ApoE(-/-) perivascular VAT, and angiotensin II-induced osteopontin secretion from adipocytes was eliminated after deletion of AT(1a) receptor in adipocytes. Notably, induction of macrophage migration by conditioned medium from angiotensin II-stimulated wild-type adipocytes was suppressed by treatment with an osteopontin-neutralizing antibody, and ApoE(-/-) OPN-/- VAT transplantation more potently attenuated aortic aneurysm formation than ApoE(-/-) VAT transplantation. Our findings indicate a previously unrecognized effect of AT(1a) receptor in perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

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  • Proteomics-based analysis of lung injury induced proteins in a mouse model of common bile duct ligation 査読

    Tomohisa Sakaue, Fumiaki Shikata, Kaho Utsunomiya, Shunya Fukae, Mie Kurata, Hirotomo Nakaoka, Mikio Okazaki, Yujiro Kawanishi, Ai Kojima, Shigeki Higashiyama, Hironori Izutani

    SURGERY   161 ( 6 )   1525 - 1535   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    Background. Lung injury is a life-threatening complication in patients with liver dysfunction. We recently provided an experimental lung injury model in mouse with common bile duct ligation. In this study, we aimed to characterize the pathologic and biochemical features of lung tissues in common bile duct ligation mice using a proteomic approach.
    Methods. Common bile ducts of BALB/c mice, 8 weeks of age, were ligated operatively. CD31-expressing pulmonary cells were sorted with immunomagnetic microbeads, and protein profiles were examined by 2 dimensional gel electrophoresis. Based on the results of protein identification, immunohistochemistry and quantitative reverse transcription polymerase chain reaction were carried out in pulmonary and hepatic tissues.
    Results. Two-dimensional gel electrophoresis revealed 3 major inflammation-associated proteins exhibiting considerable increases in the number of CD31-positive pulmonary cells after common bile duct ligation. Mass spectrometry analysis identified these proteins as SerpinB 1 a (48 kDa), ANXA1 (46 kDa), and S100A9 (16 kDa). Furthermore, the 3 proteins were more highly expressed in dilated pulmonary blood vessels of common bile duct ligation mice, in which neutrophils and monocytes were prominent, as shown by immunohistochemistry. More importantly, SerpinB la mRNA and protein were significantly upregulated in the liver, whereas S100A9 and ANXA1 mRNA and protein were upregulated in the lungs, as shown by quantitative reverse transcription polymerase chain reaction and Western blotting.
    Conclusion. We identified 3 proteins that were highly expressed in the lung after common bile duct ligation using a proteomics-based approach.

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  • Eccentric Left Ventricular Hypertrophy in Aortic Stenosis Caused by Unicuspid Aortic Valve 査読

    Haruhiko Higashi, Akiyoshi Ogimoto, Katsuji Inoue, Naohito Tokunaga, Chiharuko Iio, Jun Aono, Satoshi Yoshida, Hironori Izutani, Yasuharu Tabara, Takafumi Okura, Jitsuo Higaki, Shuntaro Ikeda

    CIRCULATION JOURNAL   81 ( 6 )   895 - 897   2017年6月

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    記述言語:英語   出版者・発行元:JAPANESE CIRCULATION SOC  

    DOI: 10.1253/circj.CJ-16-0945

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  • 大動脈弁置換術における摘出大動脈弁を用いたα-SMAの発現解析

    中岡 裕智, 坂上 倫久, 村上 貴志, 阪下 裕司, 小嶋 愛, 鹿田 文昭, 打田 俊司, 八杉 巧, 泉谷 裕則

    日本外科学会定期学術集会抄録集   117回   PS - 2   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • 大動脈弁置換術患者由来の摘出大動脈弁を用いた組織学的解析

    坂上 倫久, 中岡 裕智, 鹿田 文昭, 村上 貴志, 阪下 裕司, 小嶋 愛, 打田 俊司, 八杉 巧, 泉谷 裕則

    日本心臓血管外科学会学術総会抄録集   47回   572 - 572   2017年2月

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    記述言語:日本語   出版者・発行元:(NPO)日本心臓血管外科学会  

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  • Aortic Coarctation 28 Days after an Arterial Switch Operation in a Neonate 査読

    Fumiaki Shikata, Toru Okamura, Takashi Higaki, Masahiro Okura, Ai Kojima, Shunji Uchita, Hironori Izutani

    TEXAS HEART INSTITUTE JOURNAL   43 ( 4 )   354 - 356   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TEXAS HEART INST  

    Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient.

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  • Staged Repair of Complete Sternal Cleft and Interrupted Aortic Arch Associated With PHACES Syndrome in a Very Low Birth Weight Infant 査読

    Ai Kojima, Toru Okamura, Fumiaki Shikata, Shunji Uchita, Toshiaki Yamauchi, Masaaki Ohta, Hideki Mori, Asami Tozawa, Sonoko Fujii, Yujiro Kawanishi, Takashi Higaki, Hironori Izutani

    INTERNATIONAL SURGERY   101 ( 7-8 )   313 - 317   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT COLLEGE OF SURGEONS  

    Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal malformations' (PHACES) syndrome comprises various defects that require a concrete therapeutic plan. Herein, we report a case of a very low birth weight infant with PHACES syndrome presenting complete sternal cleft, interrupted aortic arch with ventricular septal defect, and absence of communicating cerebral arteries. Due to the infant's very low birth weight, we planned staged surgery for this complex disease. First, bilateral pulmonary artery banding was performed to improve unstable hemodynamics. Then, after sufficient body weight was obtained, aortic arch and intracardiac repair was done. However, when the tracheal tube was removed 2 weeks after surgery, the patient could not breathe well due to paradoxical chest movement related to complete sternal cleft. Consequently, to improve chest wall compliance, the upper sternum was constructed with dislocated ribs. After these treatments, the patient gained adequate weight and was in stable condition. Staged surgical treatment of sternal cleft and congenital heart defects is a potential therapeutic option for PHACES syndrome, particularly in very low birth weight infants with complex cardiovascular disease.

    DOI: 10.9738/INTSURG-D-15-00228.1

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  • An unusual cause of life-threatening right-sided heart failure: undifferentiated pleomorphic sarcoma in the right ventricular outflow tract 査読

    Haruhiko Higashi, Shinji Inaba, Hironori Izutani, Takumi Sumimoto

    EUROPEAN HEART JOURNAL   37 ( 12 )   1002 - 1002   2016年3月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    DOI: 10.1093/eurheartj/ehv659

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  • Aortic prosthetic graft infection detected by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. 査読

    Kono T, Ogimoto A, Iio C, Fujimoto K, Fujii A, Uetani T, Nagai T, Nishimura K, Inoue K, Suzuki J, Hiasa G, Okayama H, Okura T, Miyagawa M, Mochizuki T, Izutani H, Higaki J

    International journal of cardiology   203   972 - 974   2016年1月

  • Features of an alternative hemodialysis method using a hemoconcentrator during cardiopulmonary bypass surgeries 査読

    M. Tagaya, M. Matsuda, M. Yakehiro, H. Izutani

    PERFUSION-UK   30 ( 4 )   318 - 322   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS LTD  

    Purpose: This study clarified the features of a hemoconcentrator-based, alternative hemodialysis (ALTHD) method that improves the speed of serum potassium (K+) concentration adjustments, compared with dilutional ultrafiltration (DUF), during cardiopulmonary bypasses.
    Methods: Standardized bovine blood was recirculated (300 ml/min) through an in vitro hemoconcentrator circuit; hematocrit, K+ and glucose levels were measured at 5-20 min after DUF or ALTHD. We evaluated DUF at dialysis speeds of 50-250 ml/min and ALTHD at speeds of 50-1000 ml/min.
    Results: ALTHD rapidly corrected K+ and glucose concentrations at speeds up to 800 ml/min. ALTHD took 8.9 min to reach a K+ level of 4.5 mmol/L, faster than DUF (12.8 min). The ALTHD efficiency curves plateaued at 600 ml/min.
    Conclusion: ALTHD allowed faster adjustment of electrolyte levels, with peak efficiency at 600 ml/min. ALTHD has possible clinical application if available for potential use during all cardiopulmonary bypass surgeries involving extracorporeal circulation.

    DOI: 10.1177/0267659114547378

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  • Redo cardiac surgery for active prosthetic valve endocarditis associated with hereditary hemorrhagic telangiectasia: report of a case 査読

    Yuki Nakamura, Fumiaki Shikata, Masahiro Ryugo, Toru Okamura, Takumi Yasugi, Hironori Izutani

    SURGERY TODAY   44 ( 12 )   2378 - 2381   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Hereditary hemorrhagic telangiectasia (HHT) is caused by an autosomal dominant gene and characterized by multiple arteriovenous malformations in several organs, leading to bleeding or shunting. These patients often suffer severe infections and heart failure, which should be managed in the perioperative period, when open heart surgery is indicated. We report a case of successful aortic root replacement for active prosthetic valve endocarditis and ventricular septal perforation in a patient with HHT, who had severe heart failure.

    DOI: 10.1007/s00595-014-0876-6

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  • The analysis of ascending aortic dilatation in patients with a bicuspid aortic valve using the ratio of the diameters of the ascending and descending aorta 査読

    Yuki Nakamura, Masahiro Ryugo, Fumiaki Shikata, Masahiro Okura, Toru Okamura, Takumi Yasugi, Hironori Izutani

    JOURNAL OF CARDIOTHORACIC SURGERY   9   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: A bicuspid aortic valve (BAV) is associated with premature valve dysfunction and abnormalities of the ascending aorta. The aim of our study was to assess the degree of ascending aortic dilatation by measuring the ratio of the dimension of the AAo to that of the descending aorta (DAo) using preoperative computerized tomography (CT).
    Methods: A review of our institutional clinical database identified 76 patients undergoing aortic valve replacement (AVR) and 73 control patients undergoing off-pump coronary artery bypass (OPCAB group) between September 2009 and April 2012.
    Results: There were 17 patients diagnosed with BAV (BAV group), and the remaining 59 patients had a tricuspid aortic valve (TAV group). The ratios of the dimensions of the AAo to that of the DAo (AAo/DAo) for each group were: BAV, 1.58 +/- 0.25; TAV, 1.32 +/- 0.11; and OPCAB, 1.29 +/- 0.12. Interestingly, the AAo/DAo of the BAV group was significantly larger than that of the other groups.
    Conclusions: Although progressive AAo dilatation for BAV is well documented, the diameter of the AAo is currently the only estimate of aortic dilatation. In this study, we report that the ratio of the AAo and DAo diameters in patients with BAV can be a new index for assessing the dilatation of the AAo and differentiating the patients with BAV from those with TAV.

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  • Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice 査読

    Fumiaki Shikata, Tomohisa Sakaue, Koh-ichi Nakashiro, Mikio Okazaki, Mie Kurata, Toru Okamura, Masahiro Okura, Masahiro Ryugo, Yuki Nakamura, Takumi Yasugi, Shigeki Higashiyama, Hironori Izutani

    PLOS ONE   9 ( 4 )   e94550   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches.
    Methods: Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses.
    Results: We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-a and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group.
    Conclusions: We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.

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  • Prospects for using a hemoconcentrator as an alternative hemodialysis method in cardiopulmonary bypass surgeries

    M. Tagaya, M. Matsuda, M. Yakehiro, H. Izutani

    Perfusion (United Kingdom)   29 ( 2 )   117 - 123   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: Cardioplegic solutions often cause high blood concentrations of potassium. The conventional hemoconcentration circuit was improved to correct electrolyte imbalances through a method involving dilutional ultrafiltration (DUF) and an alternative hemodialysis (ALTHD) method. This study aimed to determine the effectiveness of this ALTHD method. Methods: Bovine blood was used, in conjunction with a hemoconcentrator, in an experimental hemodialysis (HD) circuit to evaluate an ALTHD method. The effectiveness of the method was determined by electrolyte and hematocrit measurements following the procedure. Results: The ALTHD method corrected electrolyte levels as effectively as DUF and was less affected by dilution than DUF. Conclusion: The ALTHD method may provide faster electrolyte adjustments than DUF because its efficiency depends on both the blood and dialysate flow rates. In addition, the ALTHD method is expected to provide increased efficiency. Thus, our DUF/ALTHD circuit-switching method may be clinically useful when rapid electrolyte correction is required. © The Author(s) 2013.

    DOI: 10.1177/0267659113502831

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  • Cardiac sarcoidosis diagnosed by histological assessment of a left ventricular apical core excised for insertion of a left ventricular assist device 査読

    Masahiro Ryugo, Hironori Izutani, Toru Okamura, Fumiaki Shikata, Masahiro Okura, Yuki Nakamura, Akiyoshi Oogimoto, Jitsuo Higaki

    General Thoracic and Cardiovascular Surgery   61 ( 12 )   716 - 718   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 58-year-old male with no history of heart disease was admitted to hospital for congestive heart failure due to severe left ventricular dysfunction, and clinically diagnosed with dilated cardiomyopathy. He developed recurrent heart failure requiring several admissions to hospital and was finally referred to our institution with severe congestive heart failure. Despite medical treatment with inotropic agents, his symptoms gradually worsened. A left ventricular assist device (LVAD) was implanted together with mitral and tricuspid valve repair at 22 days after hospitalization. A histological assessment of a left ventricular apical core specimen revealed non-caseating granulomas consistent with cardiac sarcoidosis. The postoperative course was uneventful, and he remains under cardiac rehabilitation while waiting for cardiac transplantation. © 2013 The Japanese Association for Thoracic Surgery.

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  • Beating heart mitral valve repair for a patient with previous coronary bypass: a case report and review of the literature 査読

    Teruya Nakamura, Hironori Izutani, Naosumi Sekiya, Taro Nakazato, Yoshiki Sawa

    JOURNAL OF CARDIOTHORACIC SURGERY   8   187   2013年8月

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    記述言語:英語   出版者・発行元:BIOMED CENTRAL LTD  

    Mitral valve reoperation, through a median sternotomy, for a patient with patent coronary bypass grafts is technically challenging and carries higher postoperative morbidity and mortality than a primary operation. We present a case of mitral valve repair using a beating heart technique under normothermic cardiopulmonary bypass that was performed 3 years after a coronary artery bypass operation. A limited ( 10 cm) right thoracotomy was made and cardiopulmonary bypass was conducted using the ascending aortic and femoral venous cannulation. The left atrium was opened while beating was maintained. Triangular resection of the prolapsed portion of the posterior leaflet and ring annuloplasty were performed. Completeness of the repair was verified by direct visualization under beating condition and transesophageal echocardiogram. This technique is a safe and feasible option for a mitral valve reoperation that excludes re-sternotomy, extensive pericardial dissection and aortic clamping, thereby minimizes risks of bleeding, graft injury and myocardial damage.

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  • Large thrombus originating from left atrial diverticulum: a new concern for catheter ablation of atrial fibrillation. 査読

    Nagai T, Fujii A, Nishimura K, Inoue K, Suzuki J, Kido T, Nakamura M, Matsumoto Y, Izutani H, Mochizuki T, Kawachi K, Higaki J, Ogimoto A

    Circulation   124 ( 9 )   1086 - 1088   2011年8月

  • Clinical Impact of Combined Transplantation of Autologous Skeletal Myoblasts and Bone Marrow Mononuclear Cells in Patients with Severely Deteriorated Ischemic Cardiomyopathy 査読

    Tomoyuki Fujita, Taichi Sakaguchi, Sigeru Miyagawa, Atsuhiro Saito, Naosumi Sekiya, Hironori Izutani, Yoshiki Sawa

    SURGERY TODAY   41 ( 8 )   1029 - 1036   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Purpose. Simultaneous injection of autologous bone marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device (LVAD) implantation.
    Methods. Four patients (age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium.
    Results. No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7 x 10(7) to 3.0 x 10(8), and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by H(2)(15)O positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients.
    Conclusions. Combined cell transplantation is feasible for patients with severe ischemic cardiomyopathy, and functional recovery is anticipated in selected patients.

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  • Asymptomatic Giant Traumatic Right Coronary Artery Pseudoaneurysm Caused by Sternal Fracture 査読

    Daisuke Yoshioka, Hironori Izutani, Masahiro Ryugo, Kanji Kawachi, Yoshiki Sawa

    ANNALS OF THORACIC SURGERY   92 ( 2 )   E33 - E35   2011年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE INC  

    Giant traumatic coronary artery pseudoaneurysm is extremely rare, and very few cases of traumatic coronary artery aneurysm have been previously reported. We present a case of an asymptomatic, giant, traumatic right coronary artery pseudoaneurysm caused by blunt chest trauma and sternal fracture. The risk of rupture or peripheral embolization remains unclear, but we believe that pseudoaneurysm resection and coronary artery bypass grafting are adequate procedures for preventing rupture or ischemia. (Ann Thorac Surg 2011;92:e33-5) (C) 2011 by The Society of Thoracic Surgeons

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  • Mid-term outcomes of the modified Cox-maze procedure for elderly patients: a risk analysis for failure 査読

    Teruya Nakamura, Hironori Izutani, Yoshiki Sawa

    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY   12 ( 6 )   924 - 928   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Although the maze procedure is highly effective for most patients with atrial fibrillation (AF), its standardized application to elderly patients is controversial. Between 2004 and 2007, 143 patients with a mean age of 65 years of age or older underwent the modified Cox-maze procedure concomitant with other cardiac procedures. The follow-up data were available from 128 patients, and the mean followup period was 37.1 months. The overall sinus rhythm (SR) rate at the latest follow-up was 74.2%. The cumulative freedom from AF without antiarrhythmic medication was 65.2% at five years. Stroke was less prevalent in patients with a stable SR than in those with a recurrence of AF. There were two patients (1.6%) who required permanent pacemaker placement during follow-up. Multivariate analysis demonstrated that a duration of AF &gt;5 years, a fine f-wave and a dimension of the left atrium &gt;= 60 mm were independent risk factors for recurrent AF. The Cox proportional hazard model showed that the former two factors independently affected freedom from recurrence. In conclusion, the modified Cox-maze procedure was safe and beneficial for patients 65 years of age or older, supporting that the limited biatrial ablation might be sufficient for elderly patients without risk factors for recurrence. (C) 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

    DOI: 10.1510/icvts.2010.263491

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  • Pseudoaneurysm in the Left Groin due to Ruptured Knitted Dacron Graft.

    Masahiro Ryugo, Takumi Yasugi, Mitsugi Nagashima, Hironori Izutani, Toru Okamura, Fumiaki Shikata, Masashi Kawamura, Kanji Kawachi

    Annals of vascular diseases   4 ( 2 )   154 - 6   2011年

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    記述言語:英語  

    An 82-year-old man was admitted to our institution with a painful pulsating mass in the left groin. He had undergone bypass surgery with a bifurcated Cooley double velour knitted Dacron graft to treat aorto-iliac occlusive disease 21 years previously. Computed tomography demonstrated a 35-mm pseudoaneurysm near the distal anastomosis site of the graft. Opening the aneurysm revealed that the graft was disrupted along the guideline. We resected the aneurysm and interposed an expanded polytetrafluoroethylene (ePTFE) graft. Vascular surgeons should consider that grafts can fail in patients with long-term prosthetic grafts.

    DOI: 10.3400/avd.cr.10.00018

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  • Combined ablation of atrial fibrillation and minimally invasive mitral valve surgery: a case report 査読

    Hironori Izutani, Masahiro Ryugo, Fumiaki Shikata, Masashi Kawamura, Tatsuhiro Nakata, Toru Okamura, Takumi Yasugi, Mitsugi Nagashima, Kanji Kawachi

    JOURNAL OF CARDIOTHORACIC SURGERY   5   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    A partial lower inverted J sternotomy and an extended transseptal incision provide excellent exposure for minimally invasive mitral valve surgery. However, the extended trasnsseptal incision causes dividing the sinus node artery, which may result in conduction system disturbance and need for permanent pacemaker implantation. Therefore, there is a challenge in the patient who requires concomitant ablation for atrial fibrillation because of possible conduction system disturbance caused by extended transseptal incision. We describe a new strategy for combined ablation of atrial fibrillation with minimally invasive cardiac surgery by a transseptal approach to the mitral valve through a partial lower sternotomy incision. Cryoablation was performed using a T-shaped cryoprobe with a lesion set of pulmonary vein isolation and ablation of the left and right isthmus in performing mitral annuloplasty, tricuspid annuloplasty, and atrial septal defect closure through a limited sternotomy incision. This technique might minimize possible conduction system disturbance and provide good surgical result for the patients who undergo mitral valve surgery and ablation of atrial fibrillation.

    DOI: 10.1186/1749-8090-5-79

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  • Aortoventricular disruption after aortic valve replacement: a rare complication 査読

    Teruya Nakamura, Hironori Izutani, Takanori Shibukawa, Takuya Higuchi

    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY   11 ( 4 )   447 - 448   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Aortoventricular disruption after aortic valve replacement is extremely rare. A case of aortoventricular disruption following aortic valve replacement is described in detail, and related case reports are reviewed. A 76-year-old male underwent aortic valve replacement with a tissue valve using everting mattress sutures, repair of the ascending aortic aneurysm, and mitral valve repair. After cardiopulmonary bypass was terminated, pulsatile bleeding behind the aortic root was observed, which required cardiopulmonary bypass. The ventricular rupture was located just below the left coronary annulus, and appeared secondary to a tear through the ventricular myocardium by the valve sutures. The tear was internally repaired by pledgeted sutures and Dacron patch reinforcement. The patient recovered and was discharged without major complications. Although this serious complication is extremely rare, surgeons should be aware that deep everting stitches on the left coronary annulus potentially causes aortoventricular disruption. Overstretching the posterior aortoventricular junction may contribute to this type of injury. (C) 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

    DOI: 10.1510/icvts.2010.237354

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  • Flexible band versus rigid ring annuloplasty for functional tricuspid regurgitation 査読

    Hironori Izutani, Teruya Nakamura, Kanji Kawachi

    Heart International   5 ( 2 )   64 - 68   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wichtig Publishing  

    We review and compare our experience with tricuspid ring annuloplasty between usage of the Cosgrove-Edwards flexible band and the MC3 rigid ring for repair of functional tricuspid regurgitation to determine the efficacy and mid-term durability of tricuspid annuloplasty. 117 patients with functional tricuspid regurgitation undergoing open heart surgery and tricuspid valve repair from May 2005 to December 2007 were reviewed. The flexible bands were used in thirty five patients before October 2006. Since then, the rigid rings were used in the next consecutive eighty two cases. Echocardiographic evaluation of tricuspid regurgitation was performed preoperatively and postoperatively in followup schedule. The degree of tricuspid regurgitation was reduced from 2.80±0.67 to 0.71±1.0 (regurgitation severity grade: 0 to 4) in the patients with flexible bands at discharge It was from 2.68±0.70 to 0.22±0.60 in the patients with rigid rings. At thirty six months postoperative period, tricuspid regurgitation grades in patients with flexible bands and rigid rings were 0.80±0.95 and 0.36±0.77, respectively. Freedom from recurrent tricuspid regurgitation (grade 2 or 3) in patients with flexible bands and rigid rings were 68.6% and 87.8%, respectively. Recurrent tricuspid regurgitation was significantly lower in the patients with rigid rings. Although both flexible band and rigid ring annuloplasty provide low rate of recurrent tricuspid regurgitation, rigid ring annuloplasty might be more effective than flexible band annuloplasty for decreasing functional tricuspid regurgitation in immediate and mid-term postoperative periods. © H. Izutani et al., 2010.

    DOI: 10.4081/hi.2010.e13

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  • Impact of Ostial Stenosis on the Doppler Flow Profiles in Internal Thoracic Artery Graft

    YOSHITATSU Masao, NOMURA Fumikazu, IZUTANI Hironori, TODA Koichi, KATAYAMA Akira, TAMURA Kentaro, KATAYAMA Keijiro, IHARA Katsuhiko

    Circulation journal : official journal of the Japanese Circulation Society   69 ( 2 )   253 - 256   2005年1月

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    記述言語:英語   出版者・発行元:社団法人日本循環器学会  

    As ostial stenoses of internal thoracic artery (ITA) grafts rarely occur after coronary artery bypass grafting, little is known about their Doppler flow profile. This report describes changes in the Doppler flow of ITA grafts with ostial stenosis after surgical repair of the stenosis. A 54-year-old male underwent coronary artery bypass grafting (CABG) in which the left ITA was anastomosed to the left anterior descending coronary artery. The follow-up coronary angiography revealed an ostial 90% stenosis of the ITA. The patient underwent elective surgery during which the radial artery was interposed between the left subclavian artery and the ITA. Intraoperative ultrasonography was performed immediately before cut down of the ITA graft and again immediately after completion of all anastomoses. Both diastolic and systolic velocities and the velocity time integral increased more than 2-fold after the repair. Neither the diastolic-to-systolic peak velocity ratio nor the diastolic velocity time integral fraction showed remarkable change. These profiles were different from those reported previously for distal stenosis. (<i>Circ J</i> 2005; <b>69:</b> 253 - 256)<br>

    DOI: 10.1253/circj.69.253

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    その他リンク: http://search.jamas.or.jp/link/ui/2006247899

  • Plasma brain natriuretic peptide reflects left ventricular function during percutaneous cardiopulmonary support 査読

    T Ohata, T Sakakibara, H Takano, H Izutani

    ANNALS OF THORACIC SURGERY   77 ( 1 )   164 - 167   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Background. Plasma levels of brain natriuretic peptide (BNP), a cardiac hormone secreted predominantly from the ventricle, are elevated in patients with myocardial infarction, hypertension, and dilated cardiomyopathy. In this study, we assessed the usefulness of measuring BNP to evaluate left ventricular function in patients with severe heart failure receiving mechanical circulatory support.
    Methods. Plasma BNP and creatine kinase (CK)-MB levels were measured serially in 8 consecutive patients with cardiogenic shock who received percutaneous cardiopulmonary support (PCPS) at Osaka Police Hospital from August 1999 to March 2000. Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was also performed in 5 patients during PCPS; in addition, 1 patient underwent insertion of a left ventricular venting catheter and implantation of a left ventricular assist system after PCPS.
    Results. Five patients were weaned from PCPS, and 3 died. In survivors, plasma BNP and CK-MB levels correlated positively and significantly (r = 0.968, p = 0.03). After PCPS was initiated, plasma BNP levels gradually decreased in survivors, but not in patients who died (p 0.003).
    Conclusions. These results suggest that plasma BNP levels accurately reflect myocardial damage in patients undergoing PCPS. A decrease in BNP might appear to indicate improved left ventricular function and predict successful weaning from mechanical support.

    DOI: 10.1016/S0003-4975(03)01322-5

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  • Rapid enlargement of a distal arch aneurysm after endovascular stent-grafting for pseudoaneurysm: Case report 査読

    T Ohata, T Sakakibara, H Takano, H Izutani, Y Inoue

    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY   120 ( 4 )   824 - 826   2000年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY, INC  

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  • Right ventricular outflow tract reconstruction using a goretex membrane monocusp valve in infant animals 査読

    H Izutani, Gundry, SR, LA Vricella, H Xu, LL Bailey

    ASAIO JOURNAL   46 ( 5 )   553 - 555   2000年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    We examined the feasibility of using a polytetrafluoroethylene membrane (goretex) valve and transannular patch (TAP) for right ventricular outflow tract (RVOT) reconstruction in growing animal models. Eleven infant goats (Group A) and 12 infant sheep (Croup B) underwent RVOT reconstruction under cardiopulmonary bypass. In Group A, a monocusp valve was constructed of goretex, and the RVOT was roofed over utilizing a TAP of bovine pericardium. In Group B, both a monocusp valve and a TAP were constructed of goretex. Animals were sacrificed at 6 or 12 postoperative months. Two goats in Group A died at 9 days and 4 months postoperatively due to RVOT obstruction caused by thrombus formation. Seven goats in Group A and 11 in Group B showed no pressure gradient across the valve. All animals in Group B revealed mild to moderate valvular insufficiency, but no ventricular deterioration. In contrast to the bovine pericardium, which showed a prominent fibroinflammatory reaction with calcified areas causing TAP shrinkage and RVOT stenosis, there was minimal calcification and inflammatory reaction directed against the goretex valve and TAP. We conclude that goretex can be used as a material from which to create both a monocusp valve and TAP for long-term RVOT reconstruction.

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MISC

  • 心膜再生のための新規代用心膜シートの開発-New Zealand white rabbitを用いた実験-

    坂本裕司, 打田俊司, 坂上倫久, 倉田美恵, 増本純也, 岩立力, 泉谷裕則

    日本胸部外科学会定期学術集会(Web)   77th   2024年

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  • Fontan術後ePTFE導管石灰化狭窄-CFD(数値流体学),病理組織所見からその石灰化メカニズムに迫る-

    杉本愛, 太田教隆, 坂上倫久, 白石修一, 渡邉マヤ, 土田正則, 倉田美恵, 泉谷裕則

    日本胸部外科学会定期学術集会(Web)   77th   2024年

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  • ニュージーランドホワイトラビットを使用した心膜再生の研究と代用心膜の開発

    坂本裕司, 打田俊司, 坂上倫久, 倉田美恵, 増本純也, 岩立力, 泉谷裕則

    日本心臓血管外科学会学術総会(Web)   54th   2024年

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  • 張力固定型チタンケーブルとメッシュプレートを併用した胸骨固定法の検討

    檜垣知秀, 黒部裕嗣, 福西琢真, 坂上倫久, 西村隆, 泉谷裕則

    日本心臓血管外科学会雑誌   53 ( 2 )   2024年

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  • 大動脈弁石灰化を制御する遺伝子の網羅的探索研究

    薦田宗則, 坂上倫久, 坂上倫久, 濱口美香, 坂本裕司, 福西琢真, 倉田美恵, 倉田美恵, 青野潤, 黒部裕嗣, 西村隆, 山口修, 泉谷裕則

    日本胸部外科学会定期学術集会(Web)   76th   2023年

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  • 循環補助用心内留置型ポンプカテーテルImpella挿入後の大動脈弁尖の病理学的検討

    倉田美恵, 三好徹, 東晴彦, 坂上倫久, 井上勝次, 西村隆, 池田俊太郎, 泉谷裕則, 山口修, 増本純也

    脈管学(Web)   63 ( 1 )   2023年

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  • 大動脈弁石灰化におけるvalve interstitial cellsの役割

    坂上倫久, 坂上倫久, 菅野果穂, 浪口謙治, 黒部裕嗣, 福西琢真, 薦田宗則, 西村隆, 泉谷裕則

    日本心臓血管外科学会学術総会(Web)   53rd   2023年

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  • 心膜癒着における血管新生の役割解明

    坂上倫久, 坂上倫久, 薦田宗則, 倉田美恵, 黒部裕嗣, 西村隆, 久保田義顕, 東山繁樹, 泉谷裕則

    日本血管生物医学会学術集会プログラム・抄録集   31st (CD-ROM)   2023年

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  • 生体分解性素材を用いた医療デバイスの開発

    黒部裕嗣, 黒部裕嗣, 新岡俊治, 平田陽一郎, 福西琢真, 森谷友造, 倉田美恵, 坂上倫久, 檜垣高史, 泉谷裕則

    愛媛医学   42 ( 3 )   2023年

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  • 胸部大動脈瘤に対するステントグラフト内挿術後のtype IIエンドリークに対して瘤内直接穿刺による塞栓が有効であった1例

    福西琢真, 田中宏明, 本郷哲央, 八杉巧, 黒部裕嗣, 西村隆, 薦田宗則, 檜垣知秀, 坂上倫久, 泉谷裕則

    血管外科   42 ( 1 )   2023年

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  • 大動脈弁狭窄症モデルマウスの組織学的解析

    坂本裕司, 坂上倫久, 薦田宗則, 濱口美香, 山口修, 泉谷裕則

    日本胸部外科学会定期学術集会(Web)   76th   2023年

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  • 急性循環不全に対する最新の補助循環治療 当院における補助循環用ポンプカテーテル(IMPELLA)の臨床成績

    青野 潤, 稲葉 慎二, 東 晴彦, 上谷 晃由, 西村 和久, 池田 俊太郎, 井上 勝次, 薦田 宗則, 浪口 謙治, 黒部 裕嗣, 打田 俊司, 太田 教隆, 西村 隆, 泉谷 裕則, 山口 修

    人工臓器   49 ( 2 )   S - 85   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本人工臓器学会  

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  • 大動脈弁置換術における摘出大動脈弁を用いたα-SMAの発現解析

    中岡裕智, 坂上倫久, 村上貴志, 阪下裕司, 小嶋愛, 鹿田文昭, 打田俊司, 八杉巧, 泉谷裕則

    日本外科学会定期学術集会(Web)   117th   2017年

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  • Acute Ischemia Due to Coronary Spastic Angina Exaggerated Mitral Regurgitation in a Patient With Dilated-Phase Hypertrophic Cardiomyopathy

    Chiharuko Iio, Haruhiko Higashi, Kazuhisa Nishimura, Yuta Watanabe, Hironori Izutani, Takafumi Okura, Jitsuo Higaki, Shuntaro Ikeda

    JOURNAL OF CARDIAC FAILURE   22 ( 9 )   S221 - S221   2016年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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  • Fatal Right Heart Failure after Left Ventricular Assist Device Implantation for a Patient of Cardiomyopathy Following Fulminant Myocarditis

    Yuji Sakashita, Hironori Izutani, Kenji Namiguchi, Ai Kojima, Fumiaki Shikata, Shunji Uchida, Takumi Yasugi

    JOURNAL OF CARDIAC FAILURE   21 ( 10 )   S164 - S164   2015年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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  • Fusion Image of Coronary Artery and Myocardial Perfusion Using Computed Tomography

    Teruhito Kido, Akira Kuata, Teruyoshi Uetani, Yuki Tanabe, Hikaru Nishiyama, Akiyoshi Ogimoto, Hironori Izutani, Teruhito Mochizuki

    ANNALS OF THORACIC SURGERY   99 ( 2 )   715 - 715   2015年2月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE INC  

    DOI: 10.1016/j.athoracsur.2014.09.065

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  • Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages

    Tatsuhiro Nakata, Kanji Kawachi, Mitsugi Nagashima, Takumi Yasugi, Hironori Izutani, Masahiro Ryugo, Toru Okamura, Fumiaki Shikata, Hiroshi Imagawa, Hajime Yano, Hisaaki Takahashi, Junya Tanaka

    BRAIN RESEARCH   1420   114 - 124   2011年10月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    In this study, we perform a detailed analysis of the microglial and macrophage responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in Wistar rats. The rats underwent occlusion across the descending aorta for 13 min, causing paraplegia or paresis of varying severity. They were divided into four groups based on neurological assessment: sham, mild paresis, moderate paresis, and severe (complete) paraplegia. To examine the origin of microglia and macrophages in the ischemic lesion, bone marrow from rats expressing green fluorescent protein (GFP) was transplanted into test subjects one month before performing SCl/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7 d after SCl/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+))colocalized in the mild group 7 d after SCl/R. In the moderate group, BMDMs outnumbered resident microglia. A greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was observed in lesions in the severe group, relative to the moderate group. BMDMs in the severe group strongly expressed tumor necrosis factor a, interleukin-1 beta, and inducible nitric oxide synthase, in addition to IGF-1. A robust accumulation of BMDMs occupying the entire ischemic gray matter was observed only in the severe group. These results demonstrate that the magnitude of the microglial and BMDM responses varies considerably, and that it correlates with the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to exhibit both beneficial and harmful effects in severe paraplegia. (C) 2011 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2011.08.074

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  • Anomalous Subaortic Left Brachiocephalic Vein in Surgical Cases and Literature Review

    Mitsugi Nagashima, Fumiaki Shikata, Toru Okamura, Eiichi Yamamoto, Takashi Higaki, Masashi Kawamura, Masahiro Ryugo, Hironori Izutani, Hiroshi Imagawa, Shunji Uchita, Yoshitaka Okamura, Hiroyuki Suzuki, Yoshitsugu Nakamura, Osamu Tagusari, Kanji Kawachi

    CLINICAL ANATOMY   23 ( 8 )   950 - 955   2010年11月

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    記述言語:英語   出版者・発行元:WILEY  

    Anomalous subaortic left brachiocephalic vein (ASLBV) is a rare systemic venous anomaly. We review our experience with patients associated with ASLBV who underwent cardiac surgery at three institutions. From 1989 to 2009, the medical records of surgically treated patients with ASLBV were analyzed; the incidence of ASLBV, clinical characteristics, and associated anatomical findings were assessed. Fifteen patients had ASLBV. All ASLBVs coursed left lateral to the aortic arch, passed under the ascending aorta anterior to the central pulmonary artery, and joined the right brachiocephalic vein. Fourteen patients had congenital heart disease (CHD), and the remaining patient did not have cardiac anomalies. Its incidence was 0.57% (14 of 2,449) in patients with CHD and only 0.02% (1 of 4,805) in patients without CHD. In patients with CHD, 73.3% (11 of 15) of the patients had conotruncal cardiac anomalies such as tetralogy of Fallot, ventricular septal defect with pulmonary atresia, truncus arteriosus, and interruption of the aortic arch. Eight patients had aortic arch anomalies, including right aortic arch and cervical aortic arch. The deletion of chromosomal 22q11.2 was confirmed in two patients, and one patient was diagnosed with DiGeorge syndrome. ASLBV was clinically silent even without any surgical intervention. ASLBV is a very rare anomaly and is highly associated with conotruncal cardiac anomalies and aortic arch anomalies, including right aortic arch and cervical aortic arch. Preoperative diagnosis is important when any surgical interventions are intended, especially, in patients with conotruncal cardiac anomalies. Clin. Anat. 23:950-955, 2010. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/ca.21046

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共同研究・競争的資金等の研究課題

  • 動物モデルを用いた大動脈弁狭窄症の発症から重症化までの包括的理解

    2024年4月 - 2028年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    坂本 裕司, 坂上 倫久, 泉谷 裕則

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 心臓血管外科治療で用いる生体材料の石灰化メカニズムの包括的理解

    2024年4月 - 2028年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    泉谷 裕則, 杉本 愛, 坂上 倫久, 薦田 宗則, 黒部 裕嗣, 倉田 美恵

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    配分額:18590000円 ( 直接経費:14300000円 、 間接経費:4290000円 )

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  • Neutrophil extracellular trapsを介した心膜癒着メカニズムの解明とその制御法の開発

    2023年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    薦田 宗則, 坂上 倫久, 泉谷 裕則

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 単一細胞レベルでの大動脈弁石灰化機構の統合的理解

    2022年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    坂上 倫久, 高橋 宏隆, 青野 潤, 倉田 美恵, 泉谷 裕則

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    配分額:17290000円 ( 直接経費:13300000円 、 間接経費:3990000円 )

    大動脈弁において石灰化や線維化が起こると大動脈弁狭窄症を発症し、無処置の場合には心不全により突然死に至ることがある。従って、大動脈弁組織における石灰化の分子メカニズムを明らかにすることは非常に重要である。最近、大動脈弁石灰化には弁間質細胞の骨芽細胞への分化が重要であるとの報告があり、異所性の骨芽細胞分化分子機構解明が、AS治療法確立に重要であると言われている。本年度は、外科的手術によって得られたヒト石灰化大動脈弁組織から弁間質細胞を単離培養し、トランスクリプトーム解析によって骨芽細胞のマーカーを高発現する細胞の特性解析を実施した。その結果、特定の患者においてのみ骨芽細胞や軟骨細胞のみで発現する遺伝子を高発現することがわかった。これらの石灰化を誘発する細胞は、正常弁では全く認められないものの、大動脈弁組織の中でも石灰化病変周囲で増殖しており、石灰化への寄与が強く示唆された。現在、これらの細胞をシングルセルレベルで遺伝子発現プロファイルを解析しており、大動脈弁間質細胞の中でも骨芽細胞へ分化誘導されやすい細胞と、分化誘導を受けにくい細胞それぞれの細胞特性を明らかにする。また、非石灰化大動脈弁組織由来弁間質細胞を用いた骨芽細胞分化誘導実験を実施しており、これらの細胞分化過程におけるシングルセルトランスクリプトーム解析も並行して実施しており、現在データを詳しく解析している。

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  • 単一細胞レベルでの大動脈弁石灰化機構の統合的理解

    2022年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    坂上 倫久, 高橋 宏隆, 青野 潤, 倉田 美恵, 泉谷 裕則

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    配分額:17290000円 ( 直接経費:13300000円 、 間接経費:3990000円 )

    動脈硬化関連疾患の一つとして知られる大動脈弁狭窄症は、大動脈弁組織に石灰化が生じることが特徴である。正常弁では、大動脈弁間質に大動脈弁間質細胞が局在しており、その弁尖組織全体は弁内皮細胞によって被覆されることで大動脈弁間質の恒常性が維持されている。これまでの先行研究から、大動脈弁狭窄症は弁間質細胞を起源とした骨芽細胞への分化が重要であると報告されており、骨芽細部への分化制御シグナルを解明することは大動脈弁石灰化の予防治療法の開発へとつながると考えられている。本研究ではその大動脈弁間質細胞から骨芽細胞へと分化する分化系譜をシングルセルレベルで理解することを目的としている。今年度では、トランスクリプトーム解析から骨芽細胞への分化を制御するための新たな遺伝子を特定した。この遺伝子は弁間質細胞の細胞骨格を制御する遺伝子であり、大動脈弁組織における役割については不明であった。In vitro系の実験において、弁間質細胞から骨芽細胞へと分化させるアッセイにおいて本遺伝子を発現抑制すると、骨芽細胞への分化が有意に抑制された。また、この遺伝子は正常大動脈弁組織では発現がほとんど認められず、石灰化などの病態が進行した大動脈弁組織において高発現が認められることから、大動脈弁狭窄症発症に重要な役割を果たすものと考えられる。またアクチン骨格を制御する遺伝子の他に、石灰化大動脈弁組織のカルシウム沈着部位近傍に存在する病態関連細胞やそれらの細胞が発現する遺伝子発現プロファイルも新しく特定できており、これらの細胞が出現する分化系譜についても現在詳しく解析を進めている。

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  • 大動脈弁における異所性骨芽細胞分化を司る新規脂質代謝シグナルネットワークの解析

    2020年7月 - 2023年3月

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    泉谷 裕則, 坂上 倫久

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    配分額:6370000円 ( 直接経費:4900000円 、 間接経費:1470000円 )

    大動脈弁狭窄症(AS)において、細胞膜を主成分とする脂質代謝系が大動脈弁石灰化に果たす役割について明らかにすることを目指す。昨年度、大動脈弁間質細胞を起点とした骨芽細胞分化実験をモデルとして実験を進めていたが、初代培養であるため再現性の面で安定した実験データを得ることが困難であった。そこでまず、脂肪由来間葉系幹細胞から骨芽細胞への分化実験系を一つのモデルとして、骨芽細胞分化過程における脂質分子について質量分析装置を用いて定量解析した。解析の結果、骨芽細胞分化誘導後において、アラキドン酸を出発点とする多くの脂質代謝分子に発現量に変化が認められた。さらに、その中でも一部の脂質分子においてPTGS1発現抑制によって発現抑制が認められることから、骨芽細胞分化誘導に従ってPTGS1によって代謝される新たな脂質分子を発見することに成功した。次に、当該脂質分子を弁間質細胞を用いた骨芽細胞分化系に添加することで、骨芽細胞分化シグナルに与える影響について調べた。その結果、当該脂質分子は弁間質細胞の骨芽細胞への石灰化をわずかに抑制した。現在、この脂質分子代謝シグナルの上流および下流に位置する酵素に対して複数のsiRNAを用いて発現抑制し、骨芽細胞への分化におけるこれらの遺伝子に対する役割を明らかにする実験を進めている。

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  • 大動脈弁石灰化における骨芽細胞分化マスターレギュレーターの同定と機能阻害剤の開発

    2019年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    泉谷 裕則, 坂上 倫久

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    配分額:17160000円 ( 直接経費:13200000円 、 間接経費:3960000円 )

    大動脈弁狭窄症(AS)罹患率は年々増加傾向にあるが、薬物根治療法がいまだに存在しないため、基礎研究による病態解明が急務である。外科的治療によって取り出された大動脈弁を組織学的に解析すると、大動脈弁間質組織においてvon kossaにて黒色に染色される著しいカルシウム沈着が認められることから、狭窄の一つの理由は石灰化であることが知られている。また、大動脈弁間質細胞や筋線維芽細胞の異所性増殖によっても弁肥厚が起こり、これが弁狭窄の一因であることも知られている。そこで我々は、正常弁間質に存在する弁間質細胞が何らかに刺激により骨芽細胞や筋線維芽細胞へと分化し、これが弁狭窄へと発展するものと考え、細胞分化を担うマスター制御因子の同定を目指してこれまで研究を進めてきた。本年度は、これまで樹立してきた弁間質細胞から骨芽細胞へと分化誘導する実験系をベースとして、siRNAライブラリーから治療標的分子として絞り込んだ分子Xについて解析を進めてきた。分子Xはもともと精子形成などに関わる分泌タンパク質の一つであることが知られているがAS病態進展に関わるという報告はない。分子Xは骨芽細胞への細胞分化に伴って発現が著しく低下するが、siRNAを用いてノックダウンすることで、その分化速度が加速することが分かった。また、分子Xのリコンビナントタンパク質を添加することで、骨芽細胞への分化、さらにカルシウム沈着が強く抑制されることも突き止めた。つまり、分子XはAS病態進展に対して保護的に機能する分子であることが分かった。現在は当該タンパク質がAS発症を予測できる診断マーカーとして有用であるかどうか、また、治療標的分子として有用であるかについて動物実験レベルで検証を進めているところである。

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  • 大動脈弁狭窄症バイオマーカーの探索と病態発症機序の解明

    2016年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    泉谷 裕則, 坂上 倫久

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    大動脈弁狭窄症(AS)は、加齢性と、二尖弁などの先天性のものが知られているが、その発症メカニズムは未だ不明であり、薬物治療法もいまだ存在しない。本研究では、AS発症の分子機構を解明するとともに、AS早期診断のためのバイオマーカーの探索研究を実施した。その結果、大動脈弁石灰化に伴って弁間質細胞(VIC)に発現亢進する遺伝子として脂質代謝分子COX-1を同定した。COX-1はVICの骨芽細胞分化時特異的に発現亢進するが、RNA干渉法を用いて発現抑制すると骨芽細胞分化が完全に抑制されることがわかった。従って、本分子は、AS治療標的として最適である可能性が示唆された。

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  • 心移植後の慢性拒絶反応(冠動脈硬化病変)発生機序解明に関する研究

    2012年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    泉谷 裕則, 流郷 昌裕

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    配分額:5460000円 ( 直接経費:4200000円 、 間接経費:1260000円 )

    心移植後の慢性拒絶反応として移植心に生じる冠動脈硬化病変の病因は不明である。ドナー/レシピエント間の組織不適合による免疫刺激により生じるがその機序も明らかでない。ラット異所性心移植冠動脈病変発生モデルにおいて、移植心を一定期間後に取り出して、ドナーと同系のラットに再移植し、以降の再移植心への免疫刺激を回避する「戻し移植」モデルを確立。これにより移植後5日目までの免疫反応が重要であること、特に細胞性免疫の関与が重要であることを示した。またこのモデルによる免疫応答、病理組織、分子生物学的解析などを検討し、病変発生に必要な免疫機序、特にT細胞やマクロファージの関与を確認した。

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