Heavy Ion Radiation Up-regulates Cx43 and Ameliorates the Arrhythmogenic Substrates in Hearts after Myocardial Infarction.

• Project/Area Number: 17390236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tokai University
• Principal Investigator: TANABE Teruhisa Tokai University, School of Medicine, Professor, 医学部, 教授 (10119688)
• Co-Investigator(Kenkyū-buntansha): YOSHIOKA Koichiro Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (30246087) ; MORI Hidezo National Cardiovascular Center, Research Institute, Professor, 心臓生理部, 部長 (90146598) ; KODAMA Itsuo Nagoya University, Research Institute Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2006: ¥7,300,000 (Direct Cost: ¥7,300,000); Fiscal Year 2005: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: heavy ion beam / fatal ventricular arrhythmia / myocardial infarction / connexin43 / heterogeneity of repolarization / 重粒子線照射 / 心室頻拍・細動 / 活動電位光学マッピング / ギャップジャンクション

Research Abstract

Objective: If analogous connexin43 (Cx43) up-regulation is induced in the diseased heart by carbon ion, it would provide a new perspective in radiation therapy for arrhythmias. The aim of the present study is to test this hypothesis. Methods: Non-transmural myocardial infarction (MI) was created in 24 rabbits by microsphere injection into the coronary arteries. Twenty-four rabbits without MI were used as controls. Targeted external heavy ion beam irradiation (THIR; 15 Gy) was applied 2 weeks after MI with an accelerator. Results: The THIR was associated with an increase of Cx43 mRNA and protein levels in the left ventricle in control as well as in MI rabbits. In MI hearts, immunoreactive Cx43 signals were reduced in the peri-infarct zone, and the reduction was reversed by THIR. In vivo 64 epicardial potential mapping on the free wall in MI hearts revealed reduced conduction velocity, whereas dispersion of the activation-recovery interval was increased compared with controls, and these changes were reversed by THIR. Conclusions : THIR increases Cx43 expression, improves the conductivity, decreases the spatial heterogeneity of repolarization, and reduces the vulnerability of rabbit hearts to ventricular arrhythmias after MI. THIR could have an antiarrhythmic potential through an improvement of electrical coupling.

Research Products

• [Journal Article] Heavy Ion Radiation Up-regulates Cx43 and Ameliorates the Arrhythmogenic Substrates in Hearts after Myocardial Infarction. (2006)
  • Author(s): Mari Amino, Koichiro Yoshioka, Teruhisa Tanabe, Etsuro Tanaka, Hidezo Mori, Yoshiya Furusawa, Wojciech Zareba, Masatoshi Yamazaki, Harumichi Nakagawa, Haruo Honjo, Kenji Yasui, Kaichiro Kamiya, Itsuo Kodama.
  • Journal Title: Cardiovasc Res. 72(3) Pages: 412-421
  • NAID: 10019861094
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Heavy Ion Radiation Up-regulates Cx43 and Ameliorates the Arrhythmogenic Substrates in Hearts after Myocardial Infarction. (2006)
  • Author(s): Mari Amino, Koichiro Yoshioka, Teruhisa Tanabe, Etsuro Tanaka, Hidezo Mori, Yoshiya Furusawa, Wojciech Zareba, Masatoshi Yamazaki, Harumichi Nakagawa, Haruo Honjo, Kenji Yasui, Kaichiro Kamiya, Itsuo Kodama.
  • Journal Title: Cardio vase res 72 Pages: 412-421
  • NAID: 10019861094
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heavy Ion Radiation Up-regulates Cx43 and Ameliorates the Arrhythmogenic Substrates in Hearts after Myocardial Infarction. (2006)
  • Author(s): Mari Amino, Koichiro Yoshioka, Teruhisa Tanabe, Etsuro Tanaka, Hidezo Mori, Yoshiya Furusawa, Wojciech Zareba, Masatoshi Yamazaki, Harumichi Nakagawa, Haruo Honjo, Kenji Yasui, Kaichiro Kamiya, Itsuo Kodama
  • Journal Title: Cardiovasc Res. 72(3) Pages: 412-21
  • NAID: 10019861094
• [Journal Article] Combined Effects of Nifekalant and Lidocaine on the Spiral-type Reentry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium. (2005)
  • Author(s): Amino M
  • Journal Title: Circulation J 69 Pages: 576-584