Session SA3.4

Electrical Propagation Patterns in a 3D Regionally Ischemic Human Heart: A Simulation Study

E Heidenreich, JF Rodriguez, M Doblare, B Trenor, JM Ferrero*

Universidad Politecnica de Valencia
Valencia, Spain

Ventricular tachycardia and fibrillation are known to be two types of cardiac arrhythmias that usually take place during acute ischemia and frequently lead to sudden death. In this work, we have studied the different propagation patterns displayed in a human heart during acute ischemia. For this purpose, a 3-D geometrically and anatomically accurate regionally ischemic human heart was simulated. The ischemic region was located in the anterior side of the left ventricle mimicking the occlusion of the circumflex artery. Realistic heterogeneity and fiber anisotropy has been considered in the model. The electrical activity of each cell was reproduced using a modified version of the ten Tusscher 2006 action potential model. The model of regional ischemia was composed by realistically dimensioned transitional border zones (BZ) for the three main components of acute ischemia, connecting the normal zone (NZ) and the central zone (CZ) of ischemia an a thin layer of wash-out in the epicardium. In the central zone of ischemia, the extracellular potassium concentration was set to 9.9 mM to mimic hyperkalemia, the inward Na+ current and Ca2+ current through L-type channels were scaled by a factor of 0.85 to imitate acidosis, and the intracellular ATP and ADP concentration were set to 5 mM and 99 uM respectively. The stimulation protocol consisted on the delivering five stimulation pulses at normal excitation position in the endocardium of the heart at a frequency of 1.25Hz, for preconditioning the tissue, followed by an extra-stimulus located in the border zone with different coupling intervals (CI). Our simulations have shown spatial heterogeneities in the propagated action potential, as reported experimentally, throughout the regional ischemic tissue, such as resting membrane potential (-86.1 mV in NZ, and –70.3 mV in the CZ, with potentials varying between these values in the BZ). Secondly, different patterns of activation were found depending on the CI. For CIs in the range 372-382 ms, reentry occurred at the epicardium whereas the mid-myocardium remained in refractory period. The reentrant front quickly aligned and propagated along the fiber direction on the epicardium. After the first re-entrant circuit, mid-myocardial layers were excited by the reentrant wavefront causing rather complicated patterns within the ischemic zone in the epicardium due to the re-entrant wavefront coming from the mid-myocardium. These re-entrant patterns generate a pathway within the central ischemic zone through which reentrant circuits can be sustained in the epicardium for high enough CIs. In conclusion, the model predicts the generation of figure-of-eight re-entries which cross the central ischemic zone formed in the epicardial surface due to the longer refractory period of the midmyocardial layers. Also, focal activity experimentally observed in the epicardium could be caused by re-entrant wavefronts propagating in the mid-myocardium that re-emerge in the heart surface.

(Abstract Control Number: 103)