Effects of Mexiletine on the Canine Cardiovascular System Complicating Cisapride Overdose: Potential Utility of Mexiletine for the Treatment of Drug-Induced Long QT Syndrome

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The purpose of this study was to test the potential utility of mexiletine for the treatment of drug−induced long QT syndrome in vivo.Beagle dogs were anesthetized with halothane inhalation(n=7).Monophasic action potential(MAP)of the right ventricle, ECG, systemic and left ventricular pressure, cardiac output and effective refractory period(ERP)of the right ventricle were measured.The electrically vulnerable period was estimated by the difference between MAP duration and ERP.An intentionally high dose of 1 mg/kg, i.v.of cisapride decreased the heart rate, mean blood pressure, left ventricular contraction and cardiac output and prolonged the ventricular repolarization phase and ERP, in which the increment was greater in the former than in the latter, indicating the increase of electrical vulnerability.The left ventricular end−diastolic pressure and atrioventricular as well as intraventricular conduction were hardly affected.Additional administration of an antiarrhythmic dose of 3 mg/kg, i.v.of mexiletine increased the heart rate, decreased the left ventricular contraction and cardiac output, suppressed the atrioventricular as well as intraventricular conduction, and prolonged the ERP, but shortened the ventricular repolarization phase.There was no change in the afterload and preload of the left ventricle.Thus, mexiletine decreased the electrical vulnerability of the heart during cisapride overdose, suggesting that it may become a potential pharmacological strategy for drug−induced long QT syndrome.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 83(4), 327-334, 2000-08-01

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10008184759
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5501247
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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