Investigation of the pro-arrhythmic effects of domperidone by a simulation study

Recently, it was reported that domperidone might be associated with a high risk of sudden cardiac death. However, the underlying mechanism is not clear. This study investigated the pro-arrhythmic effects of domperidone using a multi-scale biophysically detailed computational model of the heart developed by ten Tusscher et al. Based on experimental data of Benoit Drolet et aI., the pharmacological effect of domperidone was simulated by dose-dependent I_kr blocking. AP profiles, conduction velocity of electrical excitation waves, pseudo electrocardiograms and vulnerable window at tissue level were analyzed to further investigate the effects of domperidone on cardiac electrophysiology. It was shown that domperidone significantly and dose-dependently prolonged action potential duration and QT interval, slowed down conduction velocity and augmented vulnerable window. With the increase of drug concentration, domperidone increased the incidence of action potential alternans and augmented the vulnerability of genesis of unidirectional conduction. This study shows that domperidone has profound and dose-dependent pro-arrhythmic effects on cardiac electro physiological properties at cellular and tissue level.