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33. Internationale Konferenz für Elektrokardiographie

Internationale Konferenz für Elektrokardiographie

Contribution Of IKs To Rabbit Ventricular Repolarization In Vivo

Meeting Abstract

  • T. Nishina - University of Tokyo, Tokyo, Japan
  • H. Nitta - University of Tokyo, Tokyo, Japan
  • K. Ito - University of Tokyo, Tokyo, Japan
  • corresponding author presenting/speaker M. Kuwahara - University of Tokyo, Tokyo, Japan
  • H. Tsubone - University of Tokyo, Tokyo, Japan

33rd International Congress on Electrocardiology. Cologne, 28.06.-01.07.2006. Düsseldorf, Köln: German Medical Science; 2007. Doc06ice053

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Veröffentlicht: 8. Februar 2007

© 2007 Nishina et al.
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Question: The anaesthetized rabbit is frequently used for assessing the QT and the proarrhythmic effects of repolarization-delaying drugs. Although the characteristics of IKs in isolated ventricular myocytes obtained from rabbit have been reported to be close to those in human, the functional role of IKs in vivo is still incompletely understood. Therefore, we investigated the contribution of IKs to ventricular repolarization in both conscious and anaesthetized rabbits.

Methods used: In conscious rabbits, ECGs were recorded using a telemetry system. Limb lead II ECGs were also recorded with atrial pacing (120 – 200 bpm) under urethane (1 g/kg, i.v.) anesthesia. Each rabbit was treated with d,l-sotarol (2.5 mg/kg, i.v.) and/or chromanol 293B (1.0 mg/kg, i.v.). RR and QT intervals were analyzed by ECG processor (Softron) or HEM (Notocord).

Results: D,l-sotarol markedly prolonged QT or QTc interval in both conscious and anaesthetized rabbits. Although chromanol 293B did not altered QTc interval in conscious rabbits, QT interval was slightly lengthened at slow pacing rates in anaesthetized rabbits. Coadministration of these drugs induced significant prolongation of QT interval comparison with d,l-sotarol alone in both conditions. These results indicate that contribution of IKs in rabbits may be little in normal ventricular repolarization. However, when IKr reduction has occurred especially at slow heart rate, IKs may largely contribute to ventricular repolarization.

Conclusion: IKs may play an important role in ventricular repolarization as a source of repolarization reserve in rabbits. Moreover, these results suggest that rabbit may be useful preclinical species for cardiovascular safety assessment of new pharmaceuticals.