In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2
Fig 5
Simulated spontaneous ectopic activity and re-entry.
a, A 500×500 square tissue model includes normal atrial myocytes, Pitx2-4 remodelled LA cells, fibrosis, and gap junctions. Simulated spontaneous ectopic activity in the tissue model with 20% Pitx2-4 cells (b), with further increased Pitx2-4 cells (c), with enhanced cell-to-cell uncoupling (d), with increased fibrosis (e), and with increased cell-to-cell uncoupling and fibrosis (f). Re-entrant waves in the drug-free Pitx2-4 settings (g) and in the presence of 2 μM flecainide (h). Note: For the #1 scenario, the diffusion coefficient (D) was set to be 100% and the ratio of normal cells, Pitx2-4 cells and fibrosis was set to be 80:20:0. For the #2 scenario, the number of Pitx2-4 cells was increased to 40% and thereby the ratio of different cell types was 40:60:0. And D was set to be 100%. For the #3 scenario, D was reduced to 30% to model cell-to-cell uncoupling and the ratio of different cell types was set to be 80:20:0. For the #4 scenario, fibrosis was increased to 2% and thereby the ratio of different cell types was 78:20:2. And D was set to be 100%. For the #5 scenario, fibrosis was increased to 2% and D was reduced to 30%. And the ratio of different cell types was 78:20:2.