Alternating conduction in the ischaemic border zone as precursor of reentrant arrhythmias: A simulation study

Aims: Here, we investigate the mechanisms underlying the onset of conduction-related arrhythmias in a three-dimensional (3D) computational model of acute regional ischaemia. Methods: Ischaemia was introduced by realistic gradients of potassium, pH, oxygen and electrical coupling in a 3D slab of ventricular tissue using the LRd model. We focused on a specific stage (10-15 min after occlusion) at which an intramural non-conductive ischaemic core (IC) surrounded by a border zone (BZ) has formed. Results: At pacing frequencies greater than 4.5 Hz, we observed narrow areas (0.5 mm wide) of 2:1 conduction blocks at the periphery of the IC. As the pacing frequency increased, the area of block widened to 9 mm and gave rise to reentry at the periphery of the BZ. Alternating conduction blocks produced discordant action potential duration (APD) alternans throughout the slab and T-wave alternans in pseudo-ECG. Slowing the recovery of the calcium current broadened the range of pacing frequencies at which blocks were observed. Hyperkalaemia alone was sufficient to induce the alternating blocks. Conclusion: Computer modelling predicts that ischaemia-related arrhythmias are triggered by calcium-mediated alternating conduction blocks in the ischaemic border zone. Alternating conduction blocks lead to intramural reentry and APD alternans.