Alternans and spiral breakup in a human ventricular tissue model Export

@article{citeulike:885563, abstract = {Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart. 10.1152/ajpheart.00109.2006}, address = {Utrecht University, Department of Theoretical Biology, Padualaan 8, 3584 CH Utrecht, The Netherlands. khwjtuss@hotmail.com}, author = {Ten Tusscher, K. H. W. J. and Panfilov, A. V.}, citeulike-article-id = {885563}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajpheart.00109.2006}, citeulike-linkout-1 = {http://ajpheart.physiology.org/cgi/content/abstract/291/3/H1088}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16565318}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16565318}, day = {1}, doi = {10.1152/ajpheart.00109.2006}, issn = {0363-6135}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {alternans, breakup, human}, month = {September}, number = {3}, pages = {H1088--1100}, posted-at = {2006-10-05 22:01:06}, priority = {2}, title = {Alternans and spiral breakup in a human ventricular tissue model}, url = {http://dx.doi.org/10.1152/ajpheart.00109.2006}, volume = {291}, year = {2006} }

TY - JOUR ID - citeulike:885563 L3 - citeulike-article-id:885563 N2 - Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart. 10.1152/ajpheart.00109.2006 IS - 3 JF - Am J Physiol Heart Circ Physiol SN - 0363-6135 AD - Utrecht University, Department of Theoretical Biology, Padualaan 8, 3584 CH Utrecht, The Netherlands. khwjtuss@hotmail.com EP - 1100 TI - Alternans and spiral breakup in a human ventricular tissue model VL - 291 SP - H1088 KW - alternans KW - breakup KW - human AU - Ten Tusscher, KHWJ AU - Panfilov, AV PY - 2006/09/01/ UR - http://dx.doi.org/10.1152/ajpheart.00109.2006 ER -