Using computational modeling to predict arrhythmogenesis and antiarrhythmic therapy

Jonathan D. Moreno, Colleen E Clancy

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The use of computational modeling to predict arrhythmia and arrhythmogenesis 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 of some drugs have to either ameliorate or paradoxically exacerbate arrhythmia. Quantification of specific arrhythmia indices is 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 Ca2+ dynamical modeling and EC coupling, neurohumoral regulation of cardiac dynamics, and cell-signaling pathways are also reviewed.

Original languageEnglish (US)
Pages (from-to)71-84
Number of pages14
JournalDrug Discovery Today: Disease Models
Volume6
Issue number3
DOIs
StatePublished - Sep 2009

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine

Fingerprint Dive into the research topics of 'Using computational modeling to predict arrhythmogenesis and antiarrhythmic therapy'. Together they form a unique fingerprint.

  • Cite this