A computational model successfully predicted the clinically relevant concentrations at which flecainide and lidocaine exacerbate, rather than ameliorate, ventricular arrhythmia.
Can a computational model accurately predict the pro-arrhythmic or anti-arrhythmic effects of flecainide and lidocaine on ventricular rhythms?
A novel computational framework accurately predicts the complex dynamic interactions of anti-arrhythmic drugs with cardiac ion channels, offering a potential virtual drug-screening system.
A long-sought, and thus far elusive, goal has been to develop drugs to manage diseases of excitability. One such disease that affects millions each year is cardiac arrhythmia, which occurs when electrical impulses in the heart become disordered, sometimes causing sudden death. Pharmacological management of cardiac arrhythmia has failed because it is not possible to predict how drugs that target cardiac ion channels, and have intrinsically complex dynamic interactions with ion channels, will alter the emergent electrical behavior generated in the heart. Here, we applied a computational model, which was informed and validated by experimental data, that defined key measurable parameters necessary to simulate the interaction kinetics of the anti-arrhythmic drugs flecainide and lidocaine with cardiac sodium channels. We then used the model to predict the effects of these drugs on normal human ventricular cellular and tissue electrical activity in the setting of a common arrhythmia trigger, spontaneous ventricular ectopy. The model forecasts the clinically relevant concentrations at which flecainide and lidocaine exacerbate, rather than ameliorate, arrhythmia. Experiments in rabbit hearts and simulations in human ventricles based on magnetic resonance images validated the model predictions. This computational framework initiates the first steps toward development of a virtual drug-screening system that models drug-channel interactions and predicts the effects of drugs on emergent electrical activity in the heart.
Moreno et al. (Wed,) conducted a other in Cardiac arrhythmia. Flecainide and lidocaine (computational model) was evaluated on Prediction of drug effects on emergent electrical activity. A computational model successfully predicted the clinically relevant concentrations at which flecainide and lidocaine exacerbate, rather than ameliorate, ventricular arrhythmia.
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