Session S83.3

Post-Repolarization Refractoriness in Human Ventricular Cardiac Cells

JF Rodriguez*, EA Heidenreich, L Romero, JM Ferrero, M Doblare

University of Zaragoza
Zaragoza, Spain

Under pathologic conditions like coronary occlusion, excitability is known to outlast repolarization, a phenomenon termed postrepolarization refractoriness. In this work, we have used computer simulations to investigate the mechanisms of postrepolarization refractoriness in human cardiac cells under ischemic conditions at the cellular level. We used the tenTusscher model for the cardiac action potential, completed with the formulation of the ATP-sensitive potassium current [IK(ATP)] by Ferrero et al 1996, to simulate the electrical activity of isolated epicardial, endocardial, and midmyocardial ischemic cells. Hyperkalemia was simulated by increasing [Ko], while ischemia was simulated as the combination of hyperkalemia and IK(ATP) current activation. Action potential duration (APD) and effective refractory period (ERP) were measured after steady-state conditions had been reached. Our results show that APD progressively decreases with hyperkalemia, while ERP has a biphasic behavior (first increasing and then decreasing as hyperkalemia progress) as a consequence of postrepolarization refractoriness. Conduction velocity decreases monotonically with hyperkalemia from 71 cm/s for Ko=5.4 to 12 cm/s for Ko=11.2 mmol/L for all three types of cardiac cells. Postrepolarization refractoriness occurs for Ko above 5.4 mmol/L. For Ko=9.9 mmol/L, ERP is 446 milliseconds longer than the APD for ENDO cells, 441 milliseconds longer for EPI cells and 500 milliseconds longer for MID cells. For Ko above 10 mmol/L the ERP decreases with hyperkalemia as a consequence of the reduction in the conduction velocity. Under ischemic conditions, the conduction velocity is slightly affected with respect to hyperkalemic conditions, APD are significantly lowered while ERP losses the biphasic behavior. For Ko=9.9 mmol/L and a degree of IK(ATP) activation of 0.55%, ischemic ERP values surpasses ERP hyperkalemic values, while for Ko=11.2 mmol/L, the tissue becomes inexcitable. The delay in the inactivation of inward sodium current (h.j) as a consequence of diastolic depolarization and the competition with potassium currents (IK(ATP) and IKto) at the onset of activation appears to be the responsible for this behavior. According to our results, longer ERP values could be found in acutely ischemic tissue, thus creating areas of block that could set the stage for reentrant arrhythmias.

(Abstract Control Number: 136)