Effects of Disopyramide and Mexiletine on the Terminal Repolarization Process of the In Situ Heart Assessed Using the Halothane-Anesthetized In Vivo Canine Model.
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- Yoshida Hiroshi
- Second Department of Internal Medicine, Yamanashi Medical University
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- Sugiyama Atsushi
- Department of Pharmacology, Yamanashi Medical
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- Satoh Yoshioki
- Department of Pharmacology, Yamanashi Medical
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- Ishida Yuko
- Department of Pharmacology, Yamanashi Medical
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- Kugiyama Kiyotaka
- Second Department of Internal Medicine, Yamanashi Medical University
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- Hashimoto Keitaro
- Department of Pharmacology, Yamanashi Medical
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Abstract
This study was designed to assess the effects of typical class I drugs on the terminal repolarization process of the in situ heart, which is a useful marker of the potential of drug-induced long QT syndrome. Disopyramide (0.3 and 3.0 mg/kg per 10 min, n=6) or mexiletine (0.3 and 3.0 mg/kg per 30 s, n=6) was intravenously administered to halothane-anesthetized beagle dogs under the monitoring of multiple cardiovascular parameters. Antiarrhythmic concentrations were obtained with the high dose of each drug. The low dose of disopyramide or mexiletine hardly affected any of the electrophysiological parameters assessed. The high dose of disopyramide prolonged the monophasic action potential duration (MAP90) and effective refractory period (ERP) to a similar extent, thus displacing the terminal repolarization period backward, which might provide a potential proarrhythmic substrate, particularly at a slow heart rate. On the other hand, the high dose of mexiletine shortened the MAP90, but prolonged the ERP, resulting in the disappearance of the terminal repolarization period, which could prevent premature excitation with its associated conduction slowing. These electrophysiological effects of disopyramide and mexiletine on the terminal repolarization phase may at least in part explain their clinically described antiarrhythmic and proarrhythmic properties. (Circ J 2002; 66: 857 - 862)<br>
Journal
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- Circulation Journal
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Circulation Journal 66 (9), 857-862, 2002
The Japanese Circulation Society
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Details 詳細情報について
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- CRID
- 1390282680082479104
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- NII Article ID
- 110002691010
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- NII Book ID
- AA11591968
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- COI
- 1:CAS:528:DC%2BD38Xntlaqt7k%3D
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- ISSN
- 13474820
- 13469843
- http://id.crossref.org/issn/13469843
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- PubMed
- 12224826
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed