Analysis of Arrhythmogenic Profile in a Canine Model of Chronic Atrioventricular Block by Comparing In Vitro Effects of the Class III Antiarrhythmic Drug Nifekalant on the Ventricular Action Potential Indices Between Normal Heart and Atrioventricular Block Heart
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- Takahara Akira
- Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
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- Nakamura Hideki
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Nouchi Hideaki
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Tamura Takeshi
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Tanaka Toshikazu
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Shimada Hideaki
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Tamura Miku
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Tsuruoka Noriko
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Takeda Kentaro
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Tanaka Hikaru
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Shigenobu Koki
- Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan
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- Hashimoto Keitaro
- Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
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- Sugiyama Atsushi
- Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Bibliographic Information
- Other Title
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- Analysis of Arrhythmogenic Profile in a Canine Model of Chronic Atrioventricular Block by Comparing In Vitro Effects of the Class 3 Antiarrhythmic Drug Nifekalant on the Ventricular Action Potential Indices Between Normal Heart and Atrioventricular Block Heart
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Abstract
The chronic atrioventricular block dog is a useful model for predicting the future onset of drug-induced long QT syndrome in clinical practice. To better understand the arrhythmogenic profile of this model, we recorded the action potentials of the isolated ventricular tissues in the presence and absence of the class III antiarrhythmic drug nifekalant. The action potential durations of the Purkinje fiber and free wall of the right ventricle were longer in the chronic atrioventricular block dogs than in the dogs with normal sinus rhythm. Nifekalant in concentrations of 1 and 10 μM prolonged the action potential durations of Purkinje fiber and the free wall in a concentration-dependent manner. The extent of prolongation was greater in the chronic atrioventricular block dogs than in the normal dogs. However, increase of temporal dispersion of ventricular repolarization including early afterdepolarization was not detected by nifekalant in either group of dogs, indicating lack of potential to trigger arrhythmias in vitro. These results suggest that the ventricular repolarization delay in the chronic atrioventricular block model by nifekalant may largely depend on the decreased myocardial repolarization reserve, whereas the trigger for lethal arrhythmia was not generated in the in vitro condition in contrast to the in vivo experiment.<br>
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 103 (2), 181-188, 2007
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001205176371072
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- NII Article ID
- 10024312542
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- NII Book ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 8665555
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed
