Computational analysis of vulnerability to reentry in acute myocardial ischemia

Abstract

The influence of each ischemic component (hypoxia, hyperkalemia, and acidosis) on arrhythmogenesis is controversial and difficult to study experimentally. In the present study, we investigate how the different ischemic components affect the vulnerable window (VW) for reentry using computational simulations. Simulations were performed in a 3D biventricular model that includes a realistic ischemic region and the His-Purkinje conduction system. At the cellular level, we used a modified version of the O'Hara action potential model adapted to simulate acute ischemia. Three different levels of ischemia were simulated: mild, moderate, and severe. The effects on the width of the VW of each ischemic parameter were analyzed. The model allowed us to obtain a realistic reentrant pattern corresponding to ventricular tachycardia in all simulations. Results suggest 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. The presence of Purkinje system is key to the generation of reentries.

The mechanisms of potassium loss in acute myocardial ischemia: New insights from computational simulations

“…To simulate the effects of acute myocardial ischemia at the cell membrane level, more profound changes were made to the O'Hara model [as in Carpio et al (2022)]. First, a model of the ATPsensitive potassium current (I K(ATP) ), which is absent in the O'Hara model, was formulated using the model by Ferrero et al (1996) adapted to human cardiomyocytes using data from Babenko et al (1998) by changing the maximum conductance and the sensitivity to intracellular ATP and ADP concentrations ([ATP] i and [ADP] i , respectively).…”

“…Also, the appearance of an "injury current" flowing from the ischemic zone to the normal zone has been hypothesised to induce a source-sink imbalance which could induce ectopic activity that would act as a trigger for reentry (Janse et al, 1980;Janse and van Capelle, 1982;Coronel et al, 1991;Coronel, 1994). Computer simulations have also highlighted the arrhythmogenic effects of ischemia-induced hyperkalemia in virtual 2D tissues (Ferrero et al, 2003;Tice et al, 2007;Trénor et al, 2007;Romero et al, 2009) and 3D virtual bi-ventricular heart models (Mena Tobar et al, 2018;Carpio et al, 2022).…”

Sudden cardiac death in patients with myocardial infarction: 1.5 primary prevention

“…In addition, ischemia and hypoxia after an MI will lead to the increase of myocardial vulnerability and play an important role in the generation of re-entries [53]. HRV and the presence of the high average late potentials on ECG are also independent predictors of SCD and ischemic myocardial vulnerability after an MI [54].…”