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Neuroprotective effects of amiodarone

Research Project

Project/Area Number 17K11044
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionUniversity of Yamanashi

Principal Investigator

Kotoda Masakazu  山梨大学, 大学院総合研究部, 助教 (30530133)

Co-Investigator(Kenkyū-buntansha) 石山 忠彦  山梨大学, 大学院総合研究部, 准教授 (90293448)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアミオダロン / 虚血低酸素 / ナトリウムチャネル / 脳保護作用 / ナトリウムチャネル阻害 / 脳神経作用 / イオンチャネル
Outline of Final Research Achievements

In the experiment using the distal middle cerebral artery occlusion model, amiodarone pre-treatment attenuated brain injury and improved functional outcomes via blocking the sodium channels without affecting hemodynamic parameters. In contrast, amiodarone exacerbated brain injury and neurological outcomes in the experiment using the severe hypoxic–ischemic brain injury model. Severe brain sodium accumulation and brain edema were associated with the detrimental effects of amiodarone. These results suggested that amiodarone at the clinical dose can both attenuate and exacerbate brain injury after ischemic insult by affecting sodium ion transportation depending on the clinical situation. In addition, analgesic effects of amiodarone were tested in a separate experiment. Amiodarone induced analgesic responses in a dose-dependent manner likely by blocking voltage-gated sodium channels. These results indicate that clinical doses of amiodarone can also affect nociception.

Academic Significance and Societal Importance of the Research Achievements

アミオダロンはVaughan-Williams分類Ⅲ群に分類される抗不整脈薬であり、様々な難治性不整脈の治療において広く使用されている。2013年より日本においても心肺蘇生時の使用が可能となり、アメリカ心臓協会心肺蘇生ガイドラインでも第二選択薬となっていることから、使用の拡大とともに長期的な神経学的機能への作用に関心が高まっている。アミオダロンが投与される、重症不整脈や心肺停止を来した患者には脳血管障害・虚血性心疾患・外傷などを含む多くの重大疾患の併存が認められ、これらの併存疾患の兆候となる疼痛反応へのアミオダロンの作用およびその機序の解明にも大きな意義がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

Research Products

(7 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Effects of β1-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits2020

    • Author(s)
      Asano Nobumasa、Hishiyama Sohei、Ishiyama Tadahiko、Kotoda Masakazu、Matsukawa Takashi
    • Journal Title

      BMC Pharmacology and Toxicology

      Volume: 21 Pages: 13-13

    • DOI

      10.1186/s40360-020-0394-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Amiodarone exacerbates brain injuries after hypoxic?ischemic insult in mice2019

    • Author(s)
      Kotoda Masakazu、Hishiyama Sohei、Ishiyama Tadahiko、Mitsui Kazuha、Matsukawa Takashi
    • Journal Title

      BMC Neuroscience

      Volume: 20 Pages: 62-62

    • DOI

      10.1186/s12868-019-0544-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <p>Analgesic effects of amiodarone in mouse models of pain</p>2019

    • Author(s)
      Kotoda Masakazu、Ino Hirofumi、Kumakura Yasutomo、Iijima Tetsuya、Ishiyama Tadahiko、Matsukawa Takashi
    • Journal Title

      Journal of Pain Research

      Volume: 12 Pages: 1825-1832

    • DOI

      10.2147/jpr.s196480

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroprotective effects of neurotropin in a mouse model of hypoxic-ischemic brain injury2019

    • Author(s)
      Hishiyama Sohei, Kotoda Masakazu, Ishiyama Tadahiko, Mitsui Kazuha, Matsukawa Takashi.
    • Journal Title

      Journal of Anesthesia

      Volume: 33 Pages: 495-500

    • DOI

      10.1007/s00540-019-02655-z

    • NAID

      40021971774

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neuroprotective effects of amiodarone in a mouse model of ischemic stroke2017

    • Author(s)
      Kotoda Masakazu、Ishiyama Tadahiko、Mitsui Kazuha、Hishiyama Sohei、Matsukawa Takashi
    • Journal Title

      BMC Anesthesiology

      Volume: 17 Pages: 168-174

    • DOI

      10.1186/s12871-017-0459-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Amiodarone Exacerbates Brain Injuries after Hypoxic-ischemic Insult in Mice2018

    • Author(s)
      古藤田 眞和
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Antinociceptive effect of amiodarone in mouse models of pain2018

    • Author(s)
      古藤田 眞和
    • Organizer
      2018 World Congress on Pain
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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