Electrophysiologically detailed models for transmural heterogeneity and propagation in the rabbit ventricles

Life Sciences 2007 (2007) Proc Life Sciences, PC349

Poster Communications: Electrophysiologically detailed models for transmural heterogeneity and propagation in the rabbit ventricles

O. V. Aslanidi1, R. N. Sleiman1, H. Williamson1, M. R. Boyett1, H. Zhang1

1. School of Physics & Astronomy, University of Manchester, Manchester, United Kingdom.

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Electrical differences between three primary cell types – epicardial (epi), midmyocardial (M) and endocardial (endo) – account for transmural heterogeneity of action potentials (AP) in the ventricular wall, and are believed to be important in normal functioning as well as arrhythmogenesis in the heart. We develop a new family of electrophysiologically detailed computer models to explore the effects of transmural heterogeneity and intercellular electrotonic interactions in the rabbit ventricular wall. The LabHeart model of AP in a single rabbit ventricular cell was modified to incorporate new experimental data (Rozanski et al., 1997; Tsuji et al., 2000; Xu et al., 2001) on the transmural heterogeneity of the rabbit ventricle. Densities and kinetics of several ionic currents (INa, ICaL, Ito, IK1, IKs, IKr, ICl(Ca)) were updated. Single cell models were validated to reproduce experimentally measured electrical restitution properties of epi, M and endo cells (Idriss & Wolf, 2004). Finally, the 3 single-cell models were incorporated into a 1D tissue model with an intercellular gap junctional conductance chosen to give the transmural AP propagation velocity of 0.25 m/s as reported in rabbit. The models reproduce single cell AP durations (APD), transmural APD dispersion patterns and pseudo-ECGs with feasible T-waves and QT intervals similar to those observed in experiments (Yan et al., 2001; Idriss & Wolf, 2004). In the intact tissue model, different profiles of APD dispersion (including those masking the M cell region) can be simulated by changing relative sizes of the epi, M and endo regions, which shows the importance of intercellular electrotonic interactions in modulating the transmural heterogeneity of the ventricular wall. Different proportions of the three cell types can quantitatively account for differences in APD reported between male and female rabbits. Our electrophysiologically detailed models provide a powerful computational tool for non-invasive studies of electrical phenomena within the heterogeneous ventricular wall, such as functionally induced re-entry and the role of gender differences in drug dosing during its pharmacological treatment aimed at changing the transmural APD dispersion.



Where applicable, experiments conform with Society ethical requirements.

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