Modeling Drug Effects on Personalized 3D Models of the Heart: A Simulation Study
The use of anti-arrhythmic drugs is common to treat heart rhythm disorders. Computational modeling and simulation are powerful tools that can be used to investigate the effects of specific drugs on cardiac electrophysiology. In this work a patient-specific anatomical heart model is built to study the effects of dofetilide, a drug that affects IKr current in cardiac cells. We study the multi-scale effects of the drug, from cellular to organ level, by simulating electrical propagation on tissue coupled cellular ion kinetics for several heart beats. Different cell populations configurations namely endocardial, midmyocardial and epicardial are used to test the effect of tissue heterogeneity. Results confirmed the expected effects of dofetilide at cellular level, increasing the action potential duration. Pseudo-ECGs obtained for each heart beat correlated well with cellular results showing prolongation of QT segment. These techniques can be applied over the development of more complex drugs that affect multiple cellular currents.
KeywordsCardiac electrophysiology multi-scale modeling simulation drug modeling therapy planning drug cardio-toxicity
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