Cardiotoxic Local Anesthetics Increasingly Interact with Biomimetic Membranes under Ischemia-Like Acidic Conditions

DOI 機関リポジトリ Web Site Web Site PubMed 被引用文献1件 参考文献19件
  • Tsuchiya Hironori
    Department of Dental Basic Education, School of Dentistry, Asahi University
  • Mizogami Maki
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, University of Fukui
  • Ueno Takahiro
    Department of Anesthesiology, School of Dentistry, Asahi University
  • Shigemi Kenji
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, University of Fukui

この論文をさがす

抄録

The cardiotoxic effects of local anesthetics increase in cardiac ischemia which is characterized by the tissue pH lowering to 6.5 or less. Apart from the cardiac channel blockade, the membrane interaction has been referred to as another mode of their cardiotoxic action. By using biomimetic membranes, we verified the hypothesis that bupivacaine and lidocaine may increasingly interact with cardiac mitochondrial membranes under ischemia-like acidic conditions. Biomimetic membranes were prepared with different phospholipids and cholesterol to be unilamellar vesicles suspended in buffers of pH 7.4, 6.9, 6.4 or 5.9. Bupivacaine and lidocaine were reacted with the membrane preparations at cardiotoxically relevant concentrations and their membrane interactivities were determined by measuring fluorescence polarization. Both drugs interacted with 100 mol% 1,2-dipalmitoylphosphatidylcholine, peripheral nerve cell-mimetic and cardiomyocyte-mimetic membranes to increase membrane fluidity, although lowering the reaction pH from 7.4 to 5.9 decreased their membrane-fluidizing effects. In cardiomyocyte mitochondria-mimetic membranes containing 20 mol% cardiolipin, however, bupivacaine and lidocaine reversely increased their membrane interactivities at pH 5.9–6.4 compared with pH 7.4. Such increases were greater in anionic phospholipid membranes which consisted of substantial amounts of cardiolipin and phosphatidylserine. Positively charged bupivacaine and lidocaine would form ion-pairs with the negatively charged head-groups of anionic phospholipids under acidic conditions, thereby increasing the induced membrane fluidization. The mitochondrial membrane interactions depending on pH lowering may be, at least in part, responsible for local anesthetic cardiotoxicity enhanced in acidosis associated with cardiac ischemia.

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (19)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ