Computational analysis of vulnerability to reentry in acute myocardial ischemia

Edison F. Carpio1, Juan F. Gomez2, José F. Rodríguez3, Beatriz Trenor1, Jose M Ferrero4
1Universitat Politècnica de València, 2International University of Valencia, 3Politécnico di Milano, 4Ci2B, Universitat Politecnica de Valencia


Introduction: Acute myocardial ischemia is a complex process that involves different physiopathological changes (hyperkalemia, acidosis, and hypoxia). However, the influence of each ischemic component on arrhythmogenesis is difficult to study experimentally. The aim of the present study is to investigate how the different ischemic components affect the vulnerable window (VW) for reentry using computational simulations.

Methods: A 3D biventricular model of the heart including the conduction system was used to evaluate the VW for reentry. The ischemic central and border zones correspond to real data from a patient. Computational simulations were performed using a modified version of the O’Hara action potential model. Three different levels of ischemia were simulated: mild ([K+]o=8mM, ATP=8.5mM, ADP=28.75µM, pHi=7.05, pHo=7.25, LPC=2.75µM), moderate ([K+]o=10mM, ATP=7mM, ADP=57.5µM, pHi=6.9, pHo=7.1, LPC=3.5µM), and severe ([K+]o=12mM, ATP=4mM, ADP=100µM, pHi=6.6, pHo=6.8, LPC=5µM). The effects on the width of the VW of each ischemic parameter was analyzed, as well as the role of Purkinje system in reentrant circuits.

Results: Our results show a VW of ≈5 ms in moderate ischemic conditions, whereas no reentries resulted from mild or severe conditions. An individual change of hyperkalemia, hypoxia, or acidosis from moderate to severe led to an increment in the VW to 25, 45, and 40ms, respectively. Conversely, no reentry was found during the individual reduction of each ischemic parameter to a mild level. Finally, 18% of reentries disappeared when the conduction system was removed, although propagation pathways during all reentries in the Purkinje system were observed.

Conclusions: The model suggests that the ischemic level plays an important role in the generation of reentries. Furthermore, hypoxia has the most significant effect on the width of the VW. Purkinje system favors reentry through retrograde conduction.