Superior efficacy of lipid emulsion infusion over serum alkalinization in reversing amitriptyline-induced cardiotoxicity in guinea pig

• Project/Area Number: 15K10519
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Osaka City University
• Principal Investigator: MATSUURA Tadashi 大阪市立大学, 大学院医学研究科, 講師 (90619793)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 三環系抗うつ薬中毒 / 脂肪乳剤 / 心筋Naチャネル / パッチクランプ / ランゲンドルフ / 三環系抗うつ薬 / ランゲンドルフ灌流実験

Outline of Final Research Achievements

In the present study, we investigated the effectiveness of lipid emulsion in reversing amitriptyline-induced cardiotoxicity compared to that of NaHCO3 administration in the guinea pig in- vivo and in isolated hearts. We also recorded voltage-gated Na+ channel currents (INa) of left ventricular cardiomyocytes using the whole-cell patch clamp technique to evaluate the effects of lipid emulsion on amitriptyline induced inhibition of Na+ channels compared to those of alkalinization. Our results of in vivo and vitro studies demonstrate that lipid emulsion has greater recovery effects on amitriptyline induced cardiotoxicity compared to alkalinization therapy.

Research Products

• [Journal Article] Superior efficacy of lipid emulsion infusion over serum alkalinization in reversing amitriptyline-induced cardiotoxicity in guinea pig (2018)
  • Author(s): Tsujikawa S, Matsuura T, Hori K, Mori T, Kuno M, Nishikawa K
  • Journal Title: Anesthesia and Analgesia Volume: 126 Issue: 4 Pages: 1159-1169
  • DOI: 10.1213/ane.0000000000002707
  • Peer Reviewed / Open Access
• [Journal Article] The significant contribution of the partitioning effect in lipid resuscitation for bupivacaine-induced cardiotoxicity: evaluation using centrifuged solution in vivo and in isolated hearts (2015)
  • Author(s): Kotaro Hori, Tadashi Matsuura, Shogo Tsujikawa, Takashi Mori, Miyuki Kuno, Kiyonobu Nishikawa
  • Journal Title: British Journal of Anaesthesia Volume: 115 Issue: 6 Pages: 935-937
  • DOI: 10.1093/bja/aev385
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Usefulness and growing need for intraoperative transthoracic echocardiography: a case series (2015)
  • Author(s): Kotaro Hori, Tadashi Matsuura, Takashi Mori, Kiyonobu Nishikawa
  • Journal Title: BMC Anesthesiology Volume: 15 Issue: 1 Pages: 1-3
  • DOI: 10.1186/s12871-015-0066-0
  • Peer Reviewed / Open Access
• [Journal Article] The utility of intra-operative three-dimensional transoesophageal echocardiography for dynamic measurement of stroke volume (2015)
  • Author(s): Koichi Suehiro, Katsuaki Tanaka , Tokuhiro Yamada, Tadashi Matsuura , Tomoharu Funao, Takashi Mori, Kiyonobu Nishikawa
  • Journal Title: Anaesthesia Volume: 70 Issue: 2 Pages: 150-159
  • DOI: 10.1111/anae.12857
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] アミトリプチリン中毒に対する脂肪乳剤の有効性－アルカリ化療法との比較－ (2016)
  • Author(s): 辻川翔吾, 松浦 正, 堀耕太郎, 森隆, 久野みゆき, 西川精宣
  • Organizer: 日本麻酔科学会第63回学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-05-27
• [Presentation] アミトリプチリン中毒に対する脂肪乳剤の有効性―アルカリ化療法との比較― (2016)
  • Author(s): 辻川翔吾、松浦 正、堀耕太郎、久野みゆき、森 隆、西川精宣
  • Organizer: 日本麻酔科学会第63回学術集会
  • Place of Presentation: 福岡国際会議場(福岡市)、福岡県
• [Presentation] Superiority of Lipid Infusion Over Serum Alkalinization in Reversal of Amitriptyline Cardiotoxicity in Guinea Pigs: 2016 Annual Meeting, American Society of Anesthesiologists (2016)
  • Author(s): Shogo Tsujikawa, Tadashi Matsuura, Kotaro Hori, Takashi Mori, Miyuki Kuno, Kiyonobu Nishikawa
  • Organizer: 2016 Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: MacCormic Place, Chicago, USA
  • Int'l Joint Research