Multiscale modelling of drug-induced effects on cardiac electrophysiological activity

Many drugs fail in the clinical trials and therefore do not reach the market due to adverse effects on cardiac electrical function. This represents a growing concern for both regulatory and pharmaceutical agencies as it translates into important socio-economic costs. Drugs affecting cardiac activity come from diverse pharmacological groups and their interaction with cardiac electrophysiology can result in increased risk of potentially life threatening arrhythmias, such as Torsade de Pointes. The mechanisms of drug interaction with the heart are very complex and the effects span from the ion channel to the whole organ level. This makes their investigation using solely experimental in vitro and in vivo techniques very difficult. Computational modelling of cardiac electrophysiological behaviour has provided insight into the mechanisms of cardiac arrhythmogenesis, with high spatio-temporal resolution, from the ion channel to the whole organ level. It therefore represents a powerful tool in investigating mechanisms of drug-induced changes in cardiac behaviour and in their pro-arrhythmic potential. This article presents a comprehensive review of the recent advances in detailed models of drug action on cardiac electrophysiological activity.