Early afterdepolarisations and ventricular arrhythmias in cardiac tissue: a computational study
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Afterdepolarisations are associated with arrhythmias in the heart, but are difficult to study experimentally. In this study we used a simplified computational model of 1D and 2D cardiac ventricular tissue, where we could control the size of the region generating afterdepolarisations, as well as the properties of the afterdepolarisation waveform. Provided the size of the afterdepolarisation region was greater than around 1 mm, propagating extrasystoles were produced in both 1D and 2D. The number of extrasystoles produced depended on the amplitude, period, and duration of the oscillatory EAD waveform. In 2D, re-entry was also initiated for specific combinations of EAD amplitude, period, and duration, with the afterdepolarisation region acting as a common pathway. The main finding from this modelling study is therefore that afterdepolarisations can act as potent sources of propagating extrasystoles, as well as a source of re-entrant activation.
KeywordsHeart Re-entry Fibrillation Excitable media Early afterdepolarisations
We would like to thank the British Heart Foundation for funding this work through the award of Project Grant PG/03/102/1582. We would also like to thank both the Integrative Biology eScience project (EPSRC GR/S72023/01) and the White Rose Grid (http://www.wrgrid.org.uk) for making computer resources available for this work. We are especially grateful to Flavio Fenton and Elizabeth Cherry from Cornell University for providing parameter sets and source code for the 4VSIM model.
- 7.Fozzard HA, Schoenberg M (1972) Strength-duration curves in cardiac Purkinje fibres: effects of liminal length and charge distribution. J Physiol 226:593–618Google Scholar
- 13.Huelsing DJ, Spitzer KW, Pollard AE (2000) Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes. Am J Physiol Heart Circ Physiol 279:H250–H259Google Scholar
- 20.Luo CH, Rudy Y (1994) A dynamic-model of the cardiac ventricular action-potential. 2. Afterdepolarizations, triggered activity, and potentiation. Circ Res 74:1097–1113Google Scholar
- 21.Nielsen PM, Le Grice IJ, Smaill BH et al (1991) Mathematical model of geometry and fibrous structure of the heart. Am J Physiol Heart Circ Physiol 260:H1365–H1378Google Scholar
- 23.Pogwizd SM, Corr PB (1990) Mechanisms underlying the development of ventricular fibrillation during early myocardial ischaemia. Circ Res 66:672–695Google Scholar
- 24.Pogwizd SM, Corr PB (1992) The contribution of nonreentrant mechanisms to malignant ventricular arrhythmias. Basic Res Cardiol 87:115–129Google Scholar
- 28.Swissa M, Qu ZL, Ohara T et al (2002) Action potential duration restitution and ventricular fibrillation due to rapid focal excitation. Am J Physiol Heart Circ Physiol 282:H1915–H1923Google Scholar
- 32.Yan G-X, Wu Y, Liu T et al (2001) Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. Circulation 103:2851–2856Google Scholar