The prevention of perioperative mortal arrhythmia : the effect of Granulocyte-Colony Stimulating Factor Administration

• Project/Area Number: 23592025
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: University of Tsukuba
• Principal Investigator: SHIMOJO Nobutake 筑波大学, 医学医療系, 講師 (20462210)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 心臓大血管外科学 / 致死性不整脈 / 顆粒球コローニー刺激因子 / 集中治療学 / 致死性不整 / up-stream治療 / G-CSF

Research Abstract

The antiarrhythmic effect of Granulocyte colony-stimulating factor (G-CSF) on hypertrophic cardiomyopathy (HCM) has not been clarified. Salt-sensitive rats were maintained on a high-salt diet as HCM models (n=17) and a low-salt as normal heart models (NH; n=5). After the treatments with 50microg/kg (i.p.) of G-CSF (9 HCMs and 2 NHs) and vehicle (8 HCMs and 3 NHs), rapid ventricular pacing was performed to evaluate the vulnerability to VT. The G-CSF reduced inducibility of VT as compared to vehicle in HCM (1 of 9 vs. 5 of 8, p=0.03). In addition, VT was not inducible in NH treated with G-CSF, although it was inducible in 1 of 3 NHs treated with vehicle. The G-CSF increased the phosphorylated Connexin-43 level as compared to vehicle in both HCM (1.4-fold vs. 1.2-fold, p<0.01) and NH (1.4-fold vs. 1-fold, p=0.04). The G-CSF is proposed as an antiarrhythmic agent in patients with HCM, because it reduces the vulnerability to VT by up-regulating the phosphorylated Connexin-43.

Research Products

• [Journal Article] Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α. (2014)
  • Author(s): Shimojo N, Jesmin S, Sakai S, Maeda S, Miyauchi T, Mizutani T, Aonuma K, Kawano S
  • Journal Title: Life Sciences Volume: (in press) Pages: 173-178
  • DOI: 10.1016/j.lfs.2014.04.025
  • NAID: 120005555622
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] nvolvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy. (2014)
  • Author(s): Sakai S, Shimojo N, Kimura T, Tajiri K, Maruyama H, Homma S, Kuga K, Mizutani T, Aonuma K, Miyauchi T.
  • Journal Title: Life Sciences Volume: 102 Pages: 98-104
  • DOI: 10.1016/j.lfs.2014.03.018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Significant reversal of cardiac upregulated endothelin-1 system in a rat model of sepsis by landiolol hydrochloride (2014)
  • Author(s): Yoshimoto Seki, Subrina Jesmin, Nobutake Shimojo, Majedul Islam, Arifur Rahman, Tanzila Khatun, Hidekazu Sakuramoto, Masami Oki, Aiko Sonobe, Junko Kamiyama, Keiichi Hagiya, Satoru Kawano, Taro Mizutani
  • Journal Title: Life Sci. Volume: S0024-3205(14) Pages: 405-6
  • Peer Reviewed
• [Journal Article] Dual blockade of endothelin action exacerbates up-regulated VEGF angiogenic signaling in the heart of lipopolysaccharide-induced endotoxemic rat model (2014)
  • Author(s): Masami Oki, Subrina Jesmin, Majedul Islam, Chinba N Mowa, Tanzila Khatun, Nobutake Shimojo, Hideaki Sakuramoto, Junko Kamiyama, Satoru Kawano, Takashi Miyauchi, Taro Mizutani
  • Journal Title: Life Sci. Volume: S0024-3205(14) Pages: 238-0
  • NAID: 120005555617
  • Peer Reviewed
• [Journal Article] Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice. (2013)
  • Author(s): Kazuko Tajiri, Nobutake Shimojo, satoshi Sakai, Tomoko Machino-Ohtsuka, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Yoshiko Tsujimura, Taizo Kimura, Akira Sato, Yasuhiro Yasutomi, Kazutaka Aonuma
  • Journal Title: Cardiovasc Drugs Ther. Volume: 27(5) Pages: 413-24
  • DOI: 10.1007/s10557-013-6464-y
  • Peer Reviewed
• [Presentation] Effects of landiolol hydrochloride, an ultra-short-actingβ-blocker, on cardiac endothelin system in a rat model of endotoxemia : a possible relevance with cardiac functional compensatory events at the early phase of sepsis (2013)
  • Author(s): Yoshimoto Seki, Nobutake Shimojo, Jesmin Subrina, Majedul Islam, Tanzila Khatun, Hideaki Sakuramoto, Junko Kamiyama, Keiichi Hagiya, Satoru Kawano, Taro Mizutani
  • Organizer: International Conference on Endothelin
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2013-09-11
• [Presentation] Inhibitory effect of Eicosapentaenoic acid on cardiomyocyte in endothelin induced hypertrophy via PPAR-α (2013)
  • Author(s): Nobutake Shimojo, Subrina Jesmin, Satoshi Sakai, Seiji Maeda, Takashi Miyauchi, Satoru Kawano, Taro Mizutani, Kazutaka Aonuma
  • Organizer: International Conference on Endothelin
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2013-09-11
• [Presentation] Dual endothelin blockade exacerbates upregulated VEGF angiogenic signaling in the heart of lipopolysaccharide -induced endotoxemic rat model (2013)
  • Author(s): Masami Oki, Subrina Jesmin, Nobutake Shimojo, Majedul Islam, Tanzila Khatun, Hideaki Sakuramoto, Junko Kamiyama, Satoru Kawano, Taro Mizutani
  • Organizer: International Conference on Endothelin
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2013-09-11
• [Presentation] Pitavastatin ameliorates experimental autoimmune myocarditis by decreased Th1/Th17 cytokines in mice (2012)
  • Author(s): Kazuko Tajiri, Nobutake Shimojo, Kazutaka Aonuma
  • Organizer: ESC Congress 2012
  • Place of Presentation: Munich, Germany
  • Year and Date: 2012-08-25
• [Presentation] G-CSF Reduces Inducibility of Ventricular Tachycardia via Up-regulation of Phosphorylated Connexin-43 in Left Ventricular Hypertrophy Model Rats (2011)
  • Author(s): Takeshi Machino, Nobutake Shimojo, Dongzhu Xu, Rumi Koshitsuka, Yuri Kameda, Hideaki Sakuramoto, Satoru Kawano, Yukio Sekiguchi, Hiroshi Tada, and Kazutaka Aonuma
  • Organizer: 日本循環器学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-04
• [Presentation] G-CSF Reduces Ventricular Tachycardia Inducibility in the Cardiac Hypertrophy via Up-regulation of Phosphorylated Connexin-43 (2011)
  • Author(s): Takeshi Machino, Nobutake Shimojo, Dongzhu Xu, Hiro Yamasaki, Miyako Igarashi, Kentaro Yoshida, Yukio Sekiguchi, Hiroshi Tada, and Kazutaka Aonuma
  • Organizer: Heart Rhythm 2011
  • Place of Presentation: San Francisco, California
  • Year and Date: 2011-05-05
• [Presentation] Granulocyte colony-stimulating factor administration reduced the inducibility of ventricular tachyarrhythmias in cardiac hypertrophied rats through phosphorylated connexin-43. (2011)
  • Author(s): Nobutake Shimojo, Takeshi Machino, Donzhu Xu, Taizo Kimura, Rumi Koshizuka, Yuri Kameda, Satoshi Sakai, Kazutaka Aonuma
  • Organizer: Basic Cardiovascular Science2011 Scientific Sessions
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] G-CSF Reduces Ventricular Tachycardia Inducibility in the Cardiac Hypertrophy via Upregulation of Phosphorylated Connexin-43.
  • Author(s): Takeshi Machino, Nobutake Shimojo, Donzhu Xu, Hiro Yamasaki, Miyako Igarashi, Yukio Sekiguchi, Hiroshi Tada, Kazutaka Aonuma.
  • Organizer: Heart Rhythm society’s 32th Annual Scientific sessions
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] G-CSF Reduces Inducibility of Ventricular Tachycardia via Up-regulation of Phosphorylated Connexin-43 in Left Ventricular Hypertrophy Model Rats.
  • Author(s): Takeshi Machino, Nobutake Shimojo, Dongzhu Xu, Rumi Koshitsuka, Yuri Kameda, Hideaki Sakuramoto, Satoru Kawano, Yukio Sekiguchi, Hiroshi Tada, and Kazutaka Aonuma
  • Organizer: 日本循環器学会学術集会総会
  • Place of Presentation: 横浜