Using computational modeling to predict arrhythmogenesis and antiarrhythmic therapy.

Drug Discovery Today. Disease Models
Jonathan D Moreno, Colleen E Clancy

Abstract

The use of computational modeling to predict arrhythmia and arrhythmogensis is a relatively new field, but has nonetheless dramatically enhanced our understanding of the physiological and pathophysiological mechanisms that lead to arrhythmia. This review summarizes recent advances in the field of computational modeling approaches with a brief review of the evolution of cellular action potential models, and the incorporation of genetic mutations to understand fundamental arrhythmia mechanisms, including how simulations have revealed situation specific mechanisms leading to multiple phenotypes for the same genotype. The review then focuses on modeling drug blockade to understand how the less-than-intuitive effects some drugs have to either ameliorate or paradoxically exacerbate arrhythmia. Quantification of specific arrhythmia indicies are discussed at each spatial scale, from channel to tissue. The utility of hERG modeling to assess altered repolarization in response to drug blockade is also briefly discussed. Finally, insights gained from Ca(2+) dynamical modeling and EC coupling, neurohumoral regulation of cardiac dynamics, and cell signaling pathways are also reviewed.

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Citations

May 7, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Massimiliano Zaniboni, Francesca Cacciani
May 7, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Barbara WiśniowskaSebastian Polak
Sep 18, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Nejib Zemzemi, Blanca Rodriguez
Sep 8, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Henry SutantoJordi Heijman
Nov 12, 2019·JACC. Basic to Translational Science·Jonathan D MorenoJonathan R Silva
May 30, 2021·Current Cardiology Reports·Xiao-Dong ZhangNipavan Chiamvimonvat

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