Key result
In a computational model of cardiac tissue, increasing the spatial scale of heterogeneity from 5 to 20 mm increased action potential duration dispersion from 49 to 102 ms and widened the susceptible window for re-entry from 31 to 86 ms.
This computational study demonstrates a close association between increased action potential duration dispersion and susceptibility to re-entrant arrhythmias.
Larger heterogeneity scales may widen re-entry windows in models; leaves open translation to clinical arrhythmia substrates.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Clayton et al. (2005) studied Ventricular arrhythmias. Increased spatial scale of heterogeneity vs. Smaller spatial scale of heterogeneity was evaluated on Action potential duration (APD) dispersion and susceptible window for re-entry. In a computational model of cardiac tissue, increasing the spatial scale of heterogeneity from 5 to 20 mm increased action potential duration dispersion from 49 to 102 ms and widened the susceptible window for re-entry from 31 to 86 ms.
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