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

Journal of Pharmacological Sciences

Takeshi Tamura¹  Keitaro Hashimoto²  Hideaki Nouchi¹  Miku Tamura¹  Koki Shigenobu¹  Hideki Nakamura¹  Hikaru Tanaka¹  Hideaki Shimada¹  Akira Takahara²  Noriko Tsuruoka¹  Atsushi Sugiyama²  Toshikazu Tanaka¹  Kentaro Takeda¹ 

[1] Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan;Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan

关键词: action potential;    chronic atrioventricular block dog;    nifekalant;   

DOI  :  10.1254/jphs.FP0061077

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(13)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.

【 授权许可】

Unknown