Antiarrhythmic drug effect analysis on a model of cardiac fiber

Pharmacological treatment of cardiac arrhythmias still arises serious questions concerning both efficacy and safety. CAST failure as well as classification based on functional characteristics revealed the arrhythmogenic potential of both class I and class III agents, but failed to identify proarrhythmic mechanisms. These study presents results from a model of the ventricle using a modified Luo-Rudy phase I cellular formulation. The model was used for studying both pro- and antiarrhythmic mechanisms of class I drugs. 'Monitoring' was performed at cellular and cardiac fiber level in normal conditions and after drug delivery. For each specific arrhythmogenic mechanism, vulnerable parameters were investigated in order to detect the appropriate agent and its delivering requirements. Simulations revealed the link between the cellular antiarrhythmic potential and a proarrhythmic effect at the multicellular level.