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

[EN] 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.This work was supported by the Secretaría de Educacion ¿ Superior, Ciencia, Tecnología e Innovacion ¿ (SENESCYT) of Ecuador CIBAE-023- 2014, by Grant PID2019-104356RB-C41 funded by MCIN/AEI/ 10.13039/501100011033, by the European Union¿s Horizon 2020 research and innovation programme under grant agreement No 101016496, by Direccion ¿ General de Política Científica de la Generalitat Valenciana (PROMETEO 2020/043), and by the ¿Programa Salvador de Madariaga 2018¿¿ of the Spanish Ministry of Science, Innovation and Universities (Grant Reference PRX18/00489).Carpio, EF.; Gómez, JF.; Rodríguez-Matas, JF.; Trenor Gomis, BA.; Ferrero De Loma-Osorio, JM. (2022). Analysis of vulnerability to reentry in acute myocardial ischemia using a realistic human heart model. Computers in Biology and Medicine. 141:1-15. https://doi.org/10.1016/j.compbiomed.2021.10503811514