A study of early afterdepolarizations in human ventricular tissue

Early afterdepolarizations (EADs) are additional small amplitude spikes during the repolarization phase of the action potential. The presence of EADs strongly correlates with the onset of dangerous cardiac arrhythmias. Most in silico studies target various mechanisms of EAD formation and are mainly performed in animal models of cardiac cells and at a single cell level. However, most EAD-related cardiac arrhythmias feature complex spatial organization. Here, we first present our recent studies on 2D spatial wave patterns in models of human ventricular tissue with EAD-shaped action potentials. Next, we report on our first steps in studies of EAD-related arrhythmias in an anatomically accurate model of the human heart. For these studies, we use a TP06 model modified to mimic the effect of certain drugs. We show that from the initial conditions representing normal excitation of the heart, we can obtain two types of complex spatial patterns of excitation: (1) of the re-entrant type produced by Ca waves and mainly manifested as a complex focal activity on the surface of the heart, due to transmural filament orientation. For a more reduced repolarizaiton reserve, we also obtain (2) complex spatial oscillatory patterns of excitation.

[1]  J Jalife,et al.  Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart. , 1997, Journal of the American College of Cardiology.

[2]  P. C. Viswanathan,et al.  Genetics of acquired long QT syndrome. , 2005, The Journal of clinical investigation.

[3]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[4]  Alexander V Panfilov,et al.  Organization of Ventricular Fibrillation in the Human Heart , 2007, Circulation research.

[5]  Ivan V. Kazbanov,et al.  A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue , 2014, PloS one.

[6]  Ivan V. Kazbanov,et al.  Decreased repolarization reserve increases defibrillation threshold by favoring early afterdepolarizations in an in silico model of human ventricular tissue. , 2015, Heart rhythm.

[7]  P F Cranefield,et al.  Action potentials, afterpotentials, and arrhythmias. , 1977, Circulation research.

[8]  K. T. ten Tusscher,et al.  Alternans and spiral breakup in a human ventricular tissue model. , 2006, American journal of physiology. Heart and circulatory physiology.

[9]  Y Rudy,et al.  Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. , 1995, Biophysical journal.

[10]  Yoram Rudy,et al.  Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation , 2011, PLoS Comput. Biol..

[11]  Y. Rudy,et al.  Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia , 1999, Nature.

[12]  James P. Keener,et al.  Mathematical physiology , 1998 .

[13]  D. Noble,et al.  A model for human ventricular tissue. , 2004, American journal of physiology. Heart and circulatory physiology.

[14]  A. Garfinkel,et al.  Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve. , 2013, Cardiovascular research.

[15]  Diana X. Tran,et al.  Bifurcation and chaos in a model of cardiac early afterdepolarizations. , 2009, Physical review letters.

[16]  A. Panfilov,et al.  A Comparative Study of Early Afterdepolarization-Mediated Fibrillation in Two Mathematical Models for Human Ventricular Cells , 2015, PloS one.