title: Impact of amiodarone and cisapride on simulated human ventricular electrophysiology and electrocardiograms.
abstract: OBJECTIVE
  Amiodarone and cisapride are both known to prolong the QT interval, yet the two drugs have different effects on arrhythmia. Cisapride can cause torsades de pointes while amiodarone is found to be anti-arrhythmic. A computational model was used to investigate the action of these two drugs.
  
  
  RESULTS
  In a biophysically detailed model, the ion current conductivities affected by both drugs were reduced in order to simulate the pharmacological effects in healthy and ischaemic cells. Furthermore, restitution curves of the action potential duration (APD), effective refractory period, conduction velocity, wavelength, and the vulnerable window were determined in a one-dimensional (1D) tissue strand. Moreover, cardiac excitation propagation was computed in a 3D model of healthy ventricles. The corresponding body surface potentials were calculated and standard 12-lead electrocardiograms were derived. Both cisapride and amiodarone caused a prolongation of the QT interval and the refractory period. However, cisapride did not significantly alter the conduction-related properties, such as e.g. the wavelength or vulnerable window, whereas amiodarone had a larger impact on them. It slightly flattened the APD restitution slope and furthermore reduced the conduction velocity and wavelength.
  
  
  CONCLUSIONS
  Both drugs show similar prolongation of the QT interval, although they present different electrophysiological properties in the single-cell as well as in tissue simulations of cardiac excitation propagation. These computer simulations help to better understand the underlying mechanisms responsible for the initiation or termination of arrhythmias caused by amiodarone and cisapride.
authors.affiliation: Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, Karlsruhe, Germany. publications@ibt.kit.edu
authors.forename: Mathias
authors.initials: M
authors.lastname: Wilhelms
authors.forename: Christian
authors.initials: C
authors.lastname: Rombach
authors.forename: Eberhard P
authors.initials: EP
authors.lastname: Scholz
authors.forename: Olaf
authors.initials: O
authors.lastname: Dössel
authors.forename: Gunnar
authors.initials: G
authors.lastname: Seemann
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology*; D020117:Cisapride / Q000008:administration & dosage*; D003198:Computer Simulation; D004360:Drug Therapy, Computer-Assisted / Q000379:methods; D004562:Electrocardiography / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage
chemical_list: D000889:Anti-Arrhythmia Agents; D017366:Serotonin Receptor Agonists; D000638:Amiodarone; D020117:Cisapride