The effects of ischemia on the ectopic activity induced by EADs computer simulation

Computer simulations have been used to study the conditions required for the development of early afterdepolarizations (EADs) in the ventricular myocardium, and their propagation to regions with acute myocardial ischemia, thus causing ectopic activity. A modified version of the Ludo-Rudy phase II model of the cardiac ventricular action potential was used, with the formulation of the ATP-sensitive K⁺ current by Ferrero et al. (1996) being adopted. The structure of ventricular cells is considered to consist of: an EAD zone, induced by increasing I_Ca currents and by decreasing I_K currents; a border zone which separates the EAD zone from the ischemic zone; another border zone, similar to the previous one, which separates the ischemic zone from the last zone (normal cells). The different characteristics of the border zone influencing the development of ectopic activity (e.g. size of the border zone, [K⁺]₀ values, etc) are also studied. The results show that ectopic activity depends both on EAD conditions and on the parameters of the border and ischemic zones. In larger border zones (20 cells), ectopic activity only occurs under high EAD conditions (a 100% increase in I_Ca and a 60% decrease in I_k). If the border zone is half as large (10 cells) ectopic activity can occur with an 80% increase in I_Ca, and in ischemic zones even with lower [K⁺]_o values. This work shows that in a myocardial region with acute ischemia the ectopic activity can be induced by the development of EADs in a nearby zone and can propagate to normal zones.