Transmural Dispersion of Repolarization Determines Scroll Wave Behavior During Ventricular Tachyarrhythmias - A Simulation Study -

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  • Haraguchi Ryo
    National Cerebral and Cardiovascular Center Research Institute
  • Ashihara Takashi
    Department of Cardiovascular and Respiratory Medicine, Heart Rhythm Center, Shiga University of Medical Science
  • Namba Tsunetoyo
    Faculty of Healthcare Sciences, Himeji Dokkyo University
  • Tsumoto Kunichika
    The Center for Advanced Medical Engineering and Informatics, Osaka University
  • Murakami Shingo
    Department of Pharmacology, Graduate School of Medicine, Osaka University
  • Kurachi Yoshihisa
    Department of Pharmacology, Graduate School of Medicine, Osaka University
  • Ikeda Takanori
    Second Department of Internal Medicine, Kyorin University School of Medicine
  • Nakazawa Kazuo
    National Cerebral and Cardiovascular Center Research Institute

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  • – A Simulation Study –

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Abstract

Background: Ventricular tachyarrhythmia is the leading cause of sudden cardiac death, and scroll wave re-entry is known to underlie this condition. Class III antiarrhythmic drugs are commonly used worldwide to treat ventricular tachyarrhythmias; however, these drugs have a proarrhythmic adverse effect and can cause Torsade de Pointes or ventricular fibrillation. Transmural dispersion of repolarization (TDR) has been suggested to be a strong indicator of ventricular tachyarrhythmia induction. However, the role of TDR during sustained scroll wave re-entry is poorly understood. The purpose of the present study was to investigate how TDR affects scroll wave behavior and to provide a novel analysis of the mechanisms that sustain tachyarrhythmias, using computer simulations. Methods and Results: Computer simulations were carried out to quantify the TDR and QT interval under a variety of IKs and IKr during transmural conduction. Simulated scroll wave re-entries were done under a variety of IKs and IKr in a ventricular wall slab model, and the scroll wave behavior and the filament dynamics (3-dimensional organizing center) were analyzed. A slight increase in TDR, but not in the QT interval, reflected antiarrhythmic properties resulting from the restraint of scroll wave breakup, whereas a marked increase in TDR was proarrhythmic, as a result of scroll wave breakup. Conclusions: The TDR determines the sustainment of ventricular tachyarrhythmias, through control of the scroll wave filament dynamics. (Circ J 2011; 75: 80-88)<br>

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