Theoretical study of cardiac transient conduction blocks on reentries induction. Applications to antiarrhythmic drugs.
Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial" (CAST) showed more recently that mortality was significantly higher in patients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1 B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the van Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384 elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs.
Bardou
A L
AL
Cardiologie Théorique, CHU Pitié-Salpétrière, Paris.
Auger
P M
PM
Chasse
J L
JL
Seigneuric
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography / Q000187:drug effects*; D006327:Heart Block / Q000139:chemically induced* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000139:chemically induced* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents