| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands; and 2University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT; and 3Division of Mathematics, University of Dundee, Dundee DD1 4HN, United Kingdom
Submitted 9 August 2003 ; accepted in final form 2 December 2003
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.
reentrant arrhythmias; human ventricular myocytes; restitution properties; spiral waves; computer simulation
This article has been cited by other articles:
|
|
 |
|
  S. Severi, E. Grandi, C. Pes, F. Badiali, F. Grandi, and A. Santoro Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico analysis Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1378 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hassel, E. P. Scholz, N. Trano, O. Friedrich, S. Just, B. Meder, D. L. Weiss, E. Zitron, S. Marquart, B. Vogel, et al. Deficient Zebrafish Ether-a-Go-Go-Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish Reggae Mutants Circulation, February 19, 2008; 117(7): 866 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Keldermann, K. H. W. J. ten Tusscher, M. P. Nash, R. Hren, P. Taggart, and A. V. Panfilov Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H764 - H774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gordon, G. Panaghie, L. Deng, K. J. Bee, T. K. Roepke, T. Krogh-Madsen, D. J. Christini, H. Ostrer, C. T. Basson, W. Chung, et al. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance Cardiovasc Res, January 1, 2008; 77(1): 98 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chen, M. L. Marquardt, D. J. Tester, K. J. Sampson, M. J. Ackerman, and R. S. Kass Mutation of an A-kinase-anchoring protein causes long-QT syndrome PNAS, December 26, 2007; 104(52): 20990 - 20995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. I. Zhu and C. E. Clancy L-type Ca2+ channel mutations and T-wave alternans: a model study Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3480 - H3489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H.W.J. Ten Tusscher and A. V. Panfilov Influence of diffuse fibrosis on wave propagation in human ventricular tissue Europace, November 1, 2007; 9(suppl_6): vi38 - vi45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Jordan and D. J. Christini Characterizing the contribution of voltage- and calcium-dependent coupling to action potential stability: implications for repolarization alternans Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2109 - H2118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H.W.J. Ten Tusscher, R. Hren, and A. V. Panfilov Organization of Ventricular Fibrillation in the Human Heart Circ. Res., June 22, 2007; 100(12): e87 - e101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vecchietti, E. Grandi, S. Severi, I. Rivolta, C. Napolitano, S. G. Priori, and S. Cavalcanti In silico assessment of Y1795C and Y1795H SCN5A mutations: implication for inherited arrhythmogenic syndromes Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H56 - H65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Cherry and F. H. Fenton A tale of two dogs: analyzing two models of canine ventricular electrophysiology Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H43 - H55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Seemann, F. B. Sachse, D. L. Weiss, L. J. Ptacek, and M. Tristani-Firouzi Modeling of IK1 mutations in human left ventricular myocytes and tissue Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H549 - H559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kurata, H. Matsuda, I. Hisatome, and T. Shibamoto Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H701 - H718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. W. J. ten Tusscher and A. V. Panfilov Alternans and spiral breakup in a human ventricular tissue model Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1088 - H1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Allouis, F. Le Bouffant, R. Wilders, D. Peroz, J.-J. Schott, J. Noireaud, H. Le Marec, J. Merot, D. Escande, and I. Baro 14-3-3 Is a Regulator of the Cardiac Voltage-Gated Sodium Channel Nav1.5 Circ. Res., June 23, 2006; 98(12): 1538 - 1546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Berecki, J. G. Zegers, Z. A. Bhuiyan, A. O. Verkerk, R. Wilders, and A. C. G. van Ginneken Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique J. Physiol., January 15, 2006; 570(2): 237 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. A. M. Kusters, M. M. Dernison, W. P. M. van Meerwijk, D. L. Ypey, A. P. R. Theuvenet, and C. C. A. M. Gielen Stabilizing Role of Calcium Store-Dependent Plasma Membrane Calcium Channels in Action-Potential Firing and Intracellular Calcium Oscillations Biophys. J., December 1, 2005; 89(6): 3741 - 3756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Verkerk, R. Wilders, E. Schulze-Bahr, L. Beekman, Z. A. Bhuiyan, J. Bertrand, L. Eckardt, D. Lin, M. Borggrefe, G. Breithardt, et al. Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome Cardiovasc Res, December 1, 2005; 68(3): 441 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. L. Protsenko, S. M. Routkevitch, V. Y. Gur'ev, L. B. Katsnelson, O. Solovyova, O. N. Lookin, A. A. Balakin, P. Kohl, and V. S. Markhasin Hybrid duplex: a novel method to study the contractile function of heterogeneous myocardium Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2733 - H2746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kurata, I. Hisatome, H. Matsuda, and T. Shibamoto Dynamical Mechanisms of Pacemaker Generation in IK1-Downregulated Human Ventricular Myocytes: Insights from Bifurcation Analyses of a Mathematical Model Biophys. J., October 1, 2005; 89(4): 2865 - 2887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Livshitz, K. Decker, G. Faber, T. O'Hara, J. Silva, Y. Rudy, K. H. W. J. ten Tusscher, D. Noble, P. J. Noble, and A. V. Panfilov Comments on "A model for human ventricular tissue" Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H453 - H453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Berecki, J. G. Zegers, A. O. Verkerk, Z. A. Bhuiyan, B. de Jonge, M. W. Veldkamp, R. Wilders, and A. C. G. van Ginneken HERG Channel (Dys)function Revealed by Dynamic Action Potential Clamp Technique Biophys. J., January 1, 2005; 88(1): 566 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Winslow and J. L. Greenstein The Ongoing Journey to Understand Heart Function Through Integrative Modeling Circ. Res., December 10, 2004; 95(12): 1135 - 1136. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Noble Modeling the Heart Physiology, August 1, 2004; 19(4): 191 - 197. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
