Dispersion of cardiac action potential duration and the initiation of re-entry: a computational study

The initiation of re-entrant cardiac arrhythmias is associated with increased dispersion of repolarisation, but the details are difficult to investigate either experimentally or clinically. We used a computational model of cardiac tissue to study systematically the association between action potential duration (APD) dispersion and susceptibility to re-entry.

We simulated a 60 x 60 mm2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1 model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm(-2). Within the central 40 x 40 mm region we introduced square regions with prolonged APD by reducing gKmax to between 0.001 and 0.003 mS mm(-2). We varied (i) the spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and (iii) cell-to-cell coupling.

Changing spatial scale from 5 to 20 mm increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to 86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2 increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to 56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient from 0.2 to 0.05 mm2 ms(-1) increased APD dispersion from 57 to 88 ms, and increased the susceptible window from 41 to 74 ms.

We found a close association between increased APD dispersion and susceptibility to re-entrant arrhythmias, when APD dispersion is increased by larger spatial scale of heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to-cell coupling.