| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
1 Department of Theoretical Biology, Utrecht University, Utrecht, Netherlands
* To whom correspondence should be addressed. E-mail: khwjtuss{at}hotmail.com.
Ventricular fibrillation 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 which occurrence requires that the slope of the APD restitution curve exceeds one. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this manuscript 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 2D 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 one (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our paper exceed one, 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.
This article has been cited by other articles:
|
|
 |
|
  L. Romero, E. Pueyo, M. Fink, and B. Rodriguez Impact of ionic current variability on human ventricular cellular electrophysiology Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1436 - H1445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Severi, C. Corsi, and E. Cerbai From in vivo plasma composition to in vitro cardiac electrophysiology and in silico virtual heart: the extracellular calcium enigma Phil Trans R Soc A, June 13, 2009; 367(1896): 2203 - 2223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. W. J. ten Tusscher, A. Mourad, M. P. Nash, R. H. Clayton, C. P. Bradley, D. J. Paterson, R. Hren, M. Hayward, A. V. Panfilov, and P. Taggart Organization of ventricular fibrillation in the human heart: experiments and models Exp Physiol, May 1, 2009; 94(5): 553 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Keldermann, K. H. W. J. ten Tusscher, M. P. Nash, C. P. Bradley, R. Hren, P. Taggart, and A. V. Panfilov A computational study of mother rotor VF in the human ventricles Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H370 - H379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Narayan, J. D. Bayer, G. Lalani, and N. A. Trayanova Action Potential Dynamics Explain Arrhythmic Vulnerability in Human Heart Failure A Clinical and Modeling Study Implicating Abnormal Calcium Handling. J. Am. Coll. Cardiol., November 25, 2008; 52(22): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Plank, L. Zhou, J. L Greenstein, S. Cortassa, R. L Winslow, B. O'Rourke, and N. A Trayanova From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales Phil Trans R Soc A, September 28, 2008; 366(1879): 3381 - 3409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sale, J. Wang, T. J. O'Hara, D. J. Tester, P. Phartiyal, J.-Q. He, Y. Rudy, M. J. Ackerman, and G. A. Robertson Physiological Properties of hERG 1a/1b Heteromeric Currents and a hERG 1b-Specific Mutation Associated With Long-QT Syndrome Circ. Res., September 26, 2008; 103(7): e81 - e95. [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]
|
|
|
|
 |
|
 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. Masse, E. Downar, V. Chauhan, E. Sevaptsidis, and K. Nanthakumar Ventricular fibrillation in myopathic human hearts: mechanistic insights from in vivo global endocardial and epicardial mapping Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2589 - H2597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Livshitz and Y. Rudy Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2854 - H2866. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
