Development of heat-conditioning method for suppressing reperfusion injury

• Project/Area Number: 17K09482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Asahikawa Medical College
• Principal Investigator: Takeuchi Toshiharu 旭川医科大学, 医学部, 講師 (10372278)
• Co-Investigator(Kenkyū-buntansha): 長谷部 直幸 旭川医科大学, 医学部, 特任教授 (30192272) ; 蓑島 暁帆 旭川医科大学, 医学部, 助教 (90645962) ; 木谷 祐也 旭川医科大学, 医学部, 特任助教 (10804809)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ヒートコンディショニング / 再灌流障害 / 熱ショックタンパク / 急性心筋梗塞 / 経皮的冠動脈インターベンション / 熱ショック蛋白 / ポストコンディショニング / 冠動脈インターベンション / 内科 / 臨床心臓学

Outline of Final Research Achievements

We found that postconditioning with repeated brief ischemia and reperfusion during reperfusion therapy for acute myocardial infarction reduces infarct size, and that the enhanced expression of heat shock protein (HSP) is involved as a mechanism of this reduction. We further developed a heat conditioning method in which hyperthermia, which is expected to enhance HSP expression, is added to postconditioning, and investigated the effect of this method on myocardial salvage. Patients with first acute myocardial infarction were randomly assigned to two groups: a control group and a heat conditioning group. The heat-conditioning group showed increased HSP72 expression in isolated leukocytes, suggesting a high rate of myocardial salvage and possible efficacy.

Academic Significance and Societal Importance of the Research Achievements

心筋梗塞の再灌流障害による致死性不整脈や重篤な微小循環障害が発生し、治療に難渋することは稀でない。ポストコンディショニングは再灌流障害の防止・梗塞サイズ縮小効果が期待でき、さらに温熱療法を組み合わせたヒート・コンディショニングは、技術的にシンプルであるため汎用性がある。またヒート・コンディショニングは新たなカテーテルデバイスや高価な薬剤を必要としないため、医療コストの抑制という観点からも優れている。本法の有効性が多数例で検証された場合、医療材料費の削減につながることが期待され、本研究の臨床的意義は高いと考える。

Research Products

• [Journal Article] Acute Myocardial Infarction in a 17-year-old High-school Girl (2021)
  • Author(s): Kawaguchi S, Hasebe T, Ohta H, Kikuchi A, Asanome A, Nishiura T, Sakamoto N, Tanabe Y, Takeuchi T, Sato N, Kawamura Y, Hasebe N.
  • Journal Title: Internal Medicine Volume: 60 Issue: 2 Pages: 259-263
  • DOI: 10.2169/internalmedicine.5437-20
  • NAID: 130007968963
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-01-15
  • Peer Reviewed / Open Access
• [Journal Article] Back somersault-induced atrioventricular nodal reentrant tachycardia ? A case of a 15-year-old promising gymnast (2021)
  • Author(s): Hayasaka Taiki、Kawamura Yuichiro、Kobayashi Yuya、Kitani Yuya、Hontani Misako、Sugiyama Eitaro、Sumitomo Kazuhiro、Tanabe Yasuko、Akasaka Kazumi、Takeuchi Toshiharu、Sato Nobuyuki、Hirasawa Kunihiko、Hasebe Naoyuki
  • Journal Title: Journal of Cardiology Cases Volume: 24 Issue: 1 Pages: 14-19
  • DOI: 10.1016/j.jccase.2020.12.004
  • Peer Reviewed
• [Journal Article] Assessment of suitable antihypertensive therapies: Combination with high‐dose amlodipine/irbesartan vs triple combination with amlodipine/irbesartan/indapamide (ASAHI‐AI study) (2020)
  • Author(s): Nakagawa Naoki、Sato Nobuyuki、Saijo Yasuaki、Morimoto Hideo、Koyama Satoshi、Ogawa Yuji、Uekita Kazumi、Maruyama Junichi、Ohta Takafumi、Nakamura Yasuhiro、Takeuchi Toshiharu、Hasebe Naoyuki、the ASAHI‐AI investigators
  • Journal Title: The Journal of Clinical Hypertension Volume: 22 Issue: 9 Pages: 1577-1584
  • DOI: 10.1111/jch.13977
  • Peer Reviewed / Open Access
• [Journal Article] Comparison between unattended automated office blood pressure and conventional office blood pressure under the environment of health checkup among Japanese general population (2020)
  • Author(s): Sakuma Hirofumi、Nakagawa Naoki、Horiuchi Kiwamu、Hayasaka Taiki、Maruyama Keisuke、Sawada Jun、Minoshima Akiho、Fujino Takayuki、Takeuchi Toshiharu、Sato Nobuyuki、Osanai Shinobu、Hasebe Naoyuki
  • Journal Title: The Journal of Clinical Hypertension Volume: 22 Issue: 10 Pages: 1800-1806
  • DOI: 10.1111/jch.14008
• [Journal Article] Unexpectedly High Prevalence of Coronary Spastic Angina in Patients With Anderson-Fabry Disease (2019)
  • Author(s): Kitani Y, Nakagawa N, Sakamoto N, Takeuchi T, Takahashi F, Momosaki K, Nakamura K, Endo F, Maruyama H, Hasebe N.
  • Journal Title: Circulation Journal Volume: 83 Issue: 2 Pages: 481-484
  • DOI: 10.1253/circj.CJ-18-0734
  • NAID: 130007557008
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-01-25
  • Peer Reviewed
• [Journal Article] High-risk screening for Anderson?Fabry disease in patients with cardiac, renal, or neurological manifestations (2019)
  • Author(s): Nakagawa Naoki、Sawada Jun、Sakamoto Naka、Takeuchi Toshiharu、Takahashi Fumihiko、Maruyama Jun-ich、Momosaki Ken、Nakamura Kimitoshi、Endo Fumio、Hasebe Naoyuki
  • Journal Title: Journal of Human Genetics Volume: 64 Issue: 9 Pages: 891-898
  • DOI: 10.1038/s10038-019-0633-1
  • Peer Reviewed
• [Journal Article] Successful Simultaneous Revascularization for Acute Limb Ischemia and Concomitant Acute Myocardial Infarction (2018)
  • Author(s): Miyake Keisuke、Kikuchi Shinsuke、Kitani Yuya、Koya Atsuhiro、Takeuchi Toshiharu、Hasebe Naoyuki、Sawa Yoshiki、Azuma Nobuyoshi
  • Journal Title: Annals of Vascular Diseases Volume: 11 Issue: 3 Pages: 361-364
  • DOI: 10.3400/avd.cr.18-00059
  • NAID: 130007485964
  • ISSN: 1881-641X, 1881-6428
  • Year and Date: 2018-09-25
  • Peer Reviewed
• [Journal Article] Cerebral Microbleeds Remain for Nine Years: A Prospective Study with Yearly Magnetic Resonance Imaging (2018)
  • Author(s): Saito Tsukasa、Kawamura Yuichiro、Sato Nobuyuki、Sugiyama Eitaro、Okada Motoi、Takeuchi Toshiharu、Akasaka Kazumi、Hasebe Naoyuki
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 27 Issue: 2 Pages: 315-320
  • DOI: 10.1016/j.jstrokecerebrovasdis.2017.09.001
  • Peer Reviewed
• [Presentation] Ischemic Post-conditioning Enhances Induction of Cardioprotective Heat Shock Protein 72 in Patients with Acute Myocardial Infarction (2017)
  • Author(s): Takeuchi T, Kitani Y, Minoshima A, Hasebe N
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research