Regional differences in the expression of cardiac ion channels in the ventricles give rise to differences in action potential shape and duration. Transmural differences have been characterised experimentally (Antzelevitch et al. 2001). These differences are likely to be important in both the initiation and evolution of re-entrant arrhythmias.

We have developed virtual ventricular tissues where cell electrophysiology is described by the biophysically detailed Luo-Rudy equations (Luo & Rudy, 1991), and anisotropic anatomy by LV and RV wedges taken from the Auckland canine ventricles (Nielsen et al. 1991). Transmural differences in repolarisation were simulated by a linear change in K⁺ conductance from 0.2 mS cm^-2 at the endocardium with an APD of 205 ms to 0.4 mS cm^-2 at the epicardium with an APD of 160 ms. The other model parameters were set to support stable re-entry in 2D as described elsewhere (Qu et al. 2000). We used an adaptive time step of between 10 and 100 ms, and a space step of 200 mm to solve the model equations. We used a diffusion coefficient of 0.001 cm² ms^-1 for the isotropic models, and 0.002 cm² ms^-1 (parallel to fibres) and 0.0005 cm² ms^-1 (perpendicular to fibres) for the anisotropic models.

We studied the evolution of a re-entrant scroll wave with a single transmural filament in the LV and RV wedges with (i) isotropic conduction, (ii) anisotropic conduction, and (iii) anisotropic conduction with regional differences in APD. In the isotropic simulations we observed a persistent single filament that shed only short-lived fragments. Rotational anisotropy caused the filament to stretch and break, and this effect was more marked in the RV wedge. Regional differences in APD increased break-up and resulted in fragmentation of the initial filament to fewer filaments in the LV wedge compared with the RV wedge. The new filaments were more persistent in the RV than in the LV wedge.

Our simulations show that regional differences in APD are able to destabilise re-entry. We have shown that these differences can act synergistically with other mechanisms to hasten break-up of a single re-entrant wave into multiple wavelet VF. This effect was more potent in the RV, where the gradients of both APD and fibre rotation are higher than in the LV.

This work has been funded by the British Heart Foundation.