Characterization of the Halothane-Anesthetized Guinea-Pig Heart as a Model to Detect the K^+ Channel Blocker-Induced QT-Interval Prolongation(Pharmacology)
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概要
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Our previous study using the urethane-anesthetized guinea-pig model has shown that an I_<Ks> blocker chromanol 293B hardly affects the QT interval itself nor potentiates the I_<Kr> blocker-induced QT-interval prolongation. The former is in good accordance with the previous results in the human isolated intact ventricular tissue, but the latter is in sharp contrast with them. In this study, we characterized the ventricular repolarization ability of a newly developed halothane-anesthetized guinea-pig model by using I_<Kr> and I_<Ks> blockers. Intravenous administration of a selective I_<Kr> blocker d-sotalol (3 mg/kg) prolonged the QT interval by +27 ms. On the other hand, intravenous administration of chromanol 293B (1 mg/kg) prolonged the QT interval by +35 ms, and additional administration of the same dose of d-sotalol further prolonged the QT interval by +48 ms. These results suggest that the abundance of the repolarization reserve among the current and previous models may be in the order of the urethane-anesthetized guinea-pig heart>human intact ventricular tissue>halothane-anesthetized guinea-pig heart. Thus, the halothane-anesthetized guinea-pig model may be considered to be more sensitive than the previous models in predicting the QT-interval prolonging effects of new drugs in patients with high risks for the acquired long QT syndrome.
- 公益社団法人日本薬学会の論文
- 2006-04-01
著者
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HASHIMOTO Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, Universit
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Sugiyama Atsushi
Department of Pharmacology, School of Medicine, Toho University, Japan
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Takahara Akira
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University
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Takahara Akira
Department Of Internal Medicine National Kawatana Hospital
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Sugiyama Atsushi
Department Of Pharmacology Yamanashi Medical University
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Sugiyama A
Department Of Pharmacology Yamanashi Medical University
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Sugiyama Atsushi
Department Of Pharmacology Yamanashi Medical College
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Sugiyama Atsushi
Department Of Pharmacology. University Of Yamanashi Yamanashi Research Center Of Cliniacl Pharmacolo
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Sugiyama Atsushi
Department Of Chemistry College Of Science Rikkyo University
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Aikawa Tokiko
Department Of Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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Sugiyama Atsushi
Department Of Pharmacology School Of Medicine Toho University
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HASHIMOTO Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
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HASHIMOTO Keitaro
Department of Phamacology, Yamanashi Medical University
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Sugiyama Atsushi
Department of Biotechnology, Faculty of Engineering, Kansai University
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Takahara Akira
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University
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