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Electrophysiologic Mechanism of Typical Atrial Flutter Termination by Nifekalant: Effect of a Pure IKr-Selective Blocking Agent

Authors

  • HIROSHIGE YAMABE M.D.,

    Corresponding author
    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    • Address for reprints: Hiroshige Yamabe, M.D., Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, 860-8556 Japan. Fax: 81-96-362-3256; e-mail: yyamabe@kumamoto-u.ac.jp

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  • YASUAKI TANAKA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • KENJI MORIHISA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • TAKASHI UEMURA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • JUNJIROH KOYAMA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • HISANORI KANAZAWA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • TADASHI HOSHIYAMA M.D.,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • HISAO OGAWA M.D.

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Authors Hiroshige Yamabe and Yasuaki Tanaka contributed equally to this work.

  • This study was party presented at the 80th Scientific Sessions of the American Heart Association, Orlando, FL, November 4–7, 2007.

  • Disclosures: None.

Abstract

Background

Little is known about the effect of nifekalant, a pure IKr-selective blocker, on typical atrial flutter (AFL) and its termination mechanism.

Methods

The effects of nifekalant on AFL were elucidated in 17 patients. During AFL, the conduction time from the lateral to septal cavotricuspid isthmus (IS) and that through the reminder of the right atrium (nIS); AFL-cycle length (CL) variability, which was quantified by the standard deviation; and the maximum difference in AFL-CL were measured before and after administration of nifekalant (0.2–0.3 mg/kg). A single extrastimulus was delivered from the lateral cavotricuspid isthmus to elucidate the resetting response curves and atrial effective refractory period (AERP) before and after administration of nifekalant.

Results

There was no significant difference in AFL-CL, IS, and nIS before and after nifekalant; however, AERP was increased after nifekalant (155 ± 22 ms vs 184 ± 32 ms, P < 0.001). The standard deviation and the maximum difference in AFL-CL were both increased after nifekalant (1.7 ± 0.7 ms vs 3.6 ± 2.3 ms, P < 0.001 and 4.1 ± 1.9 ms vs 8.5 ± 5.2 ms, P < 0.001). The total excitable gap decreased (94 ± 17 ms vs 66 ± 21 ms, P < 0.001) with rightward shift of the resetting response curves and loss of full excitability after nifekalant. In 11 patients (65%), AFL was terminated spontaneously (n = 7) or by a single extrastimulus (n = 4), which was not observed before nifekalant. Termination was associated with orthodromic block in the cavotricuspid isthmus in all patients.

Conclusions

Nifekalant increases AERP and AFL-CL variability by abolishing a fully excitable gap, without prolongation of AFL-CL. These unique effects facilitate the termination of AFL.

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