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Abstract
Intracellular action potentials were recorded from rabbit heart sinoatrial node (SAN) and atrial intact tissue preparations. The tissue-intact myocytes exhibited heterogeneous action potential waveforms and electrical restitution properties.
A generic cell ionic model was used to fit the experimental waveforms, based on a single background current and a user-defined number of time-dependent ionic currents.
In order to optimise the model parameters in the presence of electrotonic loading from neighbouring regions, an axisymmetric 2D disc model was utilised. The disc was divided into concentric electrophysiologically-distinct regions. Action potential waveforms generated from selective points were fitted to experimental recordings from tissue-intact myocytes. The root mean square of residuals was less than 5 mV for each tissue-intact myocyte.
A 3D anatomically-realistic atrial geometry was reconstructed from cryosection images of the male Visible Human, including central and peripheral SAN regions and pulmonary veins. A realistic thickness atrial wall mesh and an epicardial shell mesh were generated based on this geometry. Distinct ionic model parameters, obtained from the optimisation process, were assigned to the central and peripheral SAN, right and left atria, and pulmonary vein regions. Heterogeneous tissue conductivity values were applied in different regions to produce physiologically realistic conduction velocities (~150 cm.s^{-1}, ~ 40 cm.s^{-1} and ~ 80 cm.s^{-1} for fast and slow conducting pathways, and bulk atrial myocardium respectively). The 3D models were able to reproduce action potential waveforms similar to those recorded experimentally, including spontaneous activation of the SAN (cycle length ~ 770 ms), and electric propagation into the surrounding atrium. Several types of arrhythmia were simulated either by pacing of specific myocardial regions or induction of spontaneous activity in one of the pulmonary veins.
The novel methodology developed in this thesis allows the systemic link between experimental and computational cardiac electrophysiology, paving the way for patient-specific simulations.