Analysis of vulnerability to reentry in acute myocardial ischemia using a realistic human heart model

Electrophysiological alterations of the myocardium caused by acute ischemia constitute a pro-arrhythmic substrate
for the generation of potentially lethal arrhythmias. Experimental evidence has shown that the main
components of acute ischemia that induce these electrophysiological alterations are hyperkalemia, hypoxia (or
anoxia in complete artery occlusion), and acidosis. However, the influence of each ischemic component on the
likelihood of reentry is not completely established. Moreover, the role of the His-Purkinje system (HPS) in the
initiation and maintenance of arrhythmias is not completely understood. In the present work, we investigate how
the three components of ischemia affect the vulnerable window (VW) for reentry using computational simulations.
In addition, we analyze the role of the HPS on arrhythmogenesis. A 3D biventricular/torso human model
that includes a realistic geometry of the central and border ischemic zones with one of the most electrophysiologically
detailed model of ischemia to date, as well as a realistic cardiac conduction system, were used to assess
the VW for reentry. Four scenarios of ischemic severity corresponding to different minutes after coronary artery
occlusion were simulated. Our results suggest that ischemic severity plays an important role in the generation of
reentries. Indeed, this is the first 3D simulation study to show that ventricular arrhythmias could be generated
under moderate ischemic conditions, but not in mild and severe ischemia. Moreover, our results show that anoxia
is the ischemic component with the most significant effect on the width of the VW. Thus, a change in the level of
anoxia from moderate to severe leads to a greater increment in the VW (40 ms), in comparison with the
increment of 20 ms and 35 ms produced by the individual change in the level of hyperkalemia and acidosis,
respectively. Finally, the HPS was a necessary element for the generation of approximately 17% of reentries
obtained. The retrograde conduction from the myocardium to HPS in the ischemic region, conduction blocks in
discrete sections of the HPS, and the degree of ischemia affecting Purkinje cells, are suggested as mechanisms
that favor the generation of ventricular arrhythmias.