Interaction of specialized cardiac conduction system with antiarrhythmic drugs: a simulation study

IEEE Trans Biomed Eng. 2011 Dec;58(12):3475-8. doi: 10.1109/TBME.2011.2165213. Epub 2011 Aug 18.

Abstract

The use of antiarrhythmic drugs is common to treat heart rhythm disorders. Computational modeling and simulation are promising tools that could be used to investigate the effects of specific drugs on cardiac electrophysiology. In this paper, we study the multiscale effects of dofetilide, a drug that blocks IKr, from cellular to organ level paying special attention to its effect on heart structures, in particular the specialized cardiac conduction system (CCS). We include a model of the CCS in a patient-specific anatomical ventricular model and study the drug effects in simulations with and without a CCS. Results confirmed the expected effects of dofetilide at cellular level, increasing the action potential duration, and at organ level, prolonging the QT segment. Notable differences are shown between models with and without the CCS on action potential duration distributions. These techniques show the importance of heart heterogeneity and the global effects of the interaction of drugs with cardiac structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Anti-Arrhythmia Agents / pharmacology*
  • Computer Simulation
  • Diffusion Tensor Imaging
  • Drug Design
  • Electrocardiography
  • Heart Conduction System / anatomy & histology
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiology
  • Heart Ventricles / drug effects
  • Humans
  • Models, Cardiovascular*
  • Phenethylamines / pharmacology
  • Sulfonamides / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Sulfonamides
  • dofetilide