Electrical Activity and Reentry During Acute Regional Myocardial Ischemia: Insights From Simulations

Abstract

In this work, the authors use computer modeling to theoretically investigate the mechanisms involved in figure-of-eight reentry during acute regional myocardial ischemia, a pattern of excitation which may lead to ventricular fibrillation and sudden cardiac death. For this purpose, a modified version of the Luo-Rudy dynamic model for the action potential and ionic currents has been used, together with a two-dimensional model of the regionally ischemic ventricle. The virtual tissue comprises several realistically dimensioned and located transitional border zones for hyperkalemia, hypoxia and acidosis, simulating the substrate heterogeneity created by acute ischemia. Different types of patterns of excitation following the delivery of a premature stimulus were obtained, including figure-of-eight reentry. Action potentials and selected ionic currents which explain the reentry process are analyzed. The effect of the degree of ATP-sensitive current activation in the vulnerability to reentry is also studied. The results are in accordance with experimental observations, and demonstrate the ability of second-generation mathematical models to analyze and explain the mechanisms involved in ischemic reentry.

Computational Models of the Heart and Their Use in Assessing the Actions of Drugs

“…The varying levels of [K + ] o , I Na , I CaL and I K(ATP) in the ischemic region result in a significant dispersion of refractoriness and of conduction velocity by the mechanisms explained in (44). Figure 10B shows the spatial variation of conduction velocity, APD, and effective refractory period in the border zone, as quantified by Ferrero et al (54). Dispersion of refractoriness and of conduction velocity in regional ischemia provides the substrate for the establishment of reentrant circuits, the main mechanism of arrhythmogenesis following coronary occlusion (53,55,56).…”

“…Due to diffusion of ions and metabolites, the core of the tissue suffering from a lack of flow, that is the central ischemic zone (CIZ), is surrounded by border zones (BZ), which comprise progressive changes in electrophysiological properties between the healthy and ischemic regions. Experimental measurements of [K + ] o , oxygen, and metabolite distribution in the ischemic area (49 -53) were used by Ferrero et al (54) to develop the 2D model of regional ischemia depicted in Fig. 10A, which included the first electrophysiologically detailed model of the BZ.…”

“…Meanwhile, tissue in the CIZ recovers, allowing reentry of the wavefront from the top, and the establishment of a figure-of-eight reentrant circuit, a pattern similar to the one observed experimentally (57 -60). Simulation results shows that the degree of activation of the IK (ATP) plays an important role in vulnerability to reentry in regional ischemia (54,61).…”

Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers

“…Heterogeneity has been studied methodically in computational models using regions with prolonged refractoriness (19), elevated extracellular K ϩ concentration (1,27), cell-cell decoupling (6), or simulated ischemia (7,12,28). Common among these situations is the localized slowing of conduction, which facilitates the formation of conduction block that is a prerequisite for reentry.…”

Effect of lidocaine in acute ischemic situations: A computer modelling study

“…To introduce the heterogeneity produced by acute ischemia, we have simulated three main components: hiperkalemia (increase in the extracellular K + concentration ([K + ] o )), hypoxia (activation of the K[ATP] current) and acidosis (reduction in the availability of Na + and Ca + channels) [15,16].…”