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

Here, we investigate the mechanisms underlying the onset of conduction-related arrhythmias in a three-dimensional (3D) computational model of acute regional ischaemia. 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. 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. 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.