Development of basic technologies for the treatment of heart disease by infra-red laser irradiation.

• Project/Area Number: 15K12524
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Kobirumaki-Shimozawa Fuyu 東京慈恵会医科大学, 医学部, 助教 (40548905)
• Co-Investigator(Renkei-kenkyūsha): FUKUDA Norio 東京慈恵会医科大学, 医学部, 准教授 (30301534) ; OYAMA Kotaro 東京慈恵会医科大学, 医学部, 訪問研究員 (70632131) ; SHIMOZAWA Togo 東京大学, 理学部技術部, 技術専門職員 (00386608)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 熱パルス / in vivoイメージング / サルコメア / 心筋細胞 / 熱 / 心筋症 / 心筋 / ナノイメージング / 心筋収縮 / カルシウムイオン / 拡張性心筋症

Outline of Final Research Achievements

In the present study, we developed a high-speed (100 fps), high-resolution (20 nm) confocal microscopic system enabling simultaneous imaging of sarcomere length (SL) and the intracellular Ca concentration ([Ca]i) in left ventricular cardiomyocytes in mice in vivo. During imaging, we measured macroscopic parameters such as electrocardiogram, left ventricular pressure and the left ventricular pressure-volume relationship, simultaneous with SL and [Ca]i. By using this system, we investigated the effects of pulsed infra-red laser irradiation on cardiomyocytes labeled for the T-tubules, and found that myocyte contractions were enhanced. These findings indicate that infra-red laser irradiation is useful in promoting myocardial contraction in vivo.

Research Products

• [Journal Article] Dynamic properties of bio-motile systems as a liquid-crystalline structure (2017)
  • Author(s): Shin'ichi Ishiwata, Makito Miyazaki, Katsuhiko Sato, Koutaro Nakagome, Seine A. Shintani, Fuyu Kobirumaki-Shimozawa, Norio Fukuda, Kazuya Suzuki, Jun Takagi, Yuta Shimamoto, and Takeshi Itabashi
  • Journal Title: Mol. Cryst. Liq. Cryst. Volume: 印刷中 Issue: 1 Pages: 127-150
  • DOI: 10.1080/15421406.2017.1289445
  • Peer Reviewed / Open Access
• [Journal Article] In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart (2017)
  • Author(s): Togo Shimozawa, Erisa Hirokawa, Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Seine A. Shintani, Takako Terui, Yasuharu Kushida, Seiichi Tsukamoto, Teruyuki Fujii, Shin'ichi Ishiwata, and Norio Fukuda
  • Journal Title: Prog. Biophys. Mol. Biol. Volume: 124 Pages: 31-40
  • DOI: 10.1016/j.pbiomolbio.2016.09.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140 (2016)
  • Author(s): Seiichi Tsukamoto, Teruyuki Fujii, Kotaro Oyama, Seine A. Shintani, Togo Shimozawa, Fuyu Kobirumaki-Shimozawa, Shin’ichi Ishiwata, and Norio Fukuda
  • Journal Title: J. Gen. Physiol. Volume: 148 Issue: 4 Pages: 341-355
  • DOI: 10.1085/jgp.201611604
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nano-imaging of the beating mouse heart in vivo: Importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function. (2016)
  • Author(s): Kobirumaki-Shimozawa F, Oyama K, Shimozawa T, Mizuno A, Ohki T, Terui T, Minamisawa S, Ishiwata S, Fukuda N
  • Journal Title: Journal of General Physiology Volume: 147 Issue: 1 Pages: 53-62
  • DOI: 10.1085/jgp.201511484
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] In vivo analysis of individual sarcomere dynamics in the beating mouse heart. (2018)
  • Author(s): 小比類巻生, 大山廣太郎, 下澤東吾, 石渡信一, 福田紀男
  • Organizer: 第95回日本生理学会大会
• [Presentation] In vivo cardiac nano-imaging high-resolution analysis of excitation-contraction coupling in the heart. (2017)
  • Author(s): 小比類巻生、福田紀男
  • Organizer: 第９４回日本生理学会大会
• [Presentation] Simultaneous nano-imaging of sarcomere dynamics and local calcium in rat neonatal cardiomyocytes via expression of Yellow Cameleon-Nano140 fusion α-actinin in Z disks. (2017)
  • Author(s): 塚本精一, 大山廣太郎, 藤井輝之, 小比類巻生, 石渡信一, 福田紀男
  • Organizer: 第94回日本生理学会大会
• [Presentation] In vivoナノイメージングによる心筋収縮の可視化と熱による制御 (2016)
  • Author(s): 大山廣太郎, 小比類巻生, 下澤東吾, 福田紀男
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター, 北海道
  • Year and Date: 2016-03-22
• [Presentation] Yellow Cameleon-Nano140を用いたラット幼若心筋細胞のサルコメア長と細胞内カルシウムの同時計測系の開発 (2016)
  • Author(s): 塚本精一, 大山廣太郎, 藤井輝之, 小比類巻生, 石渡信一, 福田紀男
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター, 北海道
  • Year and Date: 2016-03-22
• [Presentation] High-speed, high-performance real-time imaging of physiological sarcomere dynamics in the beating heart in vivo. (2016)
  • Author(s): Kobirumaki-Shimozawa, Kotaro Oyama, Togo Shimozawa, Takako Terui, Shin'ichi Ishiwata, Norio Fukuda
  • Organizer: Biophysical Society 60th Annual Meeting
  • Place of Presentation: Los Angels, California, USA
  • Year and Date: 2016-02-27
  • Int'l Joint Research
• [Presentation] SIMULTANEOUS HIGH-PRECISION IMAGING OF LOCAL CALCIUM AND SINGLE SARCOMERE LENGTH IN RAT NEONATAL CARDIOMYOCYTES VIA EXPRESSION OF YELLOW CAMELEON-NANO140 IN Z-DISCS. (2016)
  • Author(s): Seiichi Taukamoto, Kotaro Oyama, Teruyuki Fujii, Fuyu Kobirumaki-Shimozawa, Seine A. Shintani, Shin'ichi Ishiwata, Norio Fukuda
  • Organizer: Biophysical Society 60th Annual Meeting
  • Place of Presentation: Los Angels, California, USA
  • Year and Date: 2016-02-27
  • Int'l Joint Research