Session S55.1

Dispersion of Refractoriness in a Simulated Ischemic 2D Tissue: Implications in Vulnerability to Reentry

B Trenor*, L Romero, JM Ferrero, J Saiz,
G Molto, V Hernandez

Universidad Politécnica de Valencia
Valencia, Spain

During the acute phase of myocardial ischemia, electrophysiological changes predispose the heart to the occurrence of ventricular arrhythmias. Reentrant excitation is an important mechanism, which may lead to disorganized electrical activity and ventricular fibrillation. Many metabolic and physiological alterations arising in the ischemic tissue and thus heterogeneities in electrical properties, such as refractoriness, set the stage for
reentry.
The aim of this computational work was to analyze the role of dispersion in refractoriness on reentry generation in a two-dimensional sheet of regionally ischemic myocardial tissue at different stages after the onset of ischemia.
A modified version of the 2000 Luo-Rudy action potential model was used in our simulations. Different stages of regional ischemia were simulated in a 2D sheet of 5.5cm×5.5cm taking into account hyperkalemia, acidosis and hypoxia in a central zone. We also included an electrophysiological border zone and normal tissue. We followed an S1-S2 stimulation protocol applied at the bottom edge of the tissue. The state of sodium channels inactivation gates was used as an indicator for refractoriness and refractory periods (RPs) were also measured in the central fiber of the tissue by stimulating prematurely in the zone where RP was sought.
Our results are consistent with experimental studies in which vulnerability to ventricular arrhythmias has an unimodal behavior in the acute phase 1A of myocardial ischemia. For early stages of ischemia (prior to minute 6.5) no reentry was originated, then the width of the vulnerable window (VW, i.e. time interval of the reentrant premature stimulus), widens and reaches the maximum value (58 ms) for minute 8. Finally the VW decays again as ischemia conditions are worsened. Patterns of activation and maps of refractory periods in the different stages of ischemia showed that dispersion in refractoriness was a necessary condition for the tissue to nest reentry. In minute 8, refractoriness map was drastically more abrupt than in early stages (minute 4) where no reentry was initiated. However, as ischemia progressed, the values of the maximum difference between the measured RP in the different zones of the tissue (an indicator of dispersion in refractoriness) followed an increasing evolution from 84 ms at minute 6.5 to 214 ms at minute 8.75. and the correlation factor yielded 0.97. This monotone increase did not present an unimodal behavior as did the VW for reentry. Indeed, the correlation between dispersion of refractoriness and the VW yielded 0.03. Our results suggest that dispersion of refractoriness is necessary for reentry to ensue, but its dispersion degree does not correlate with vulnerability. Thus, other ionic factors such as axial currents must be involved in the modulation of the vulnerability to reentry.

(Abstract Control Number: 128)