Parameter Sensitivity Analysis to Predict Action Potential Duration Alternans in Cardiac Electrophysiology Simulation

Nida Dusturia and Ki Moo Lim
Kumoh National Institute of Technology


Alternans, the beat-to-beat temporal alternation in the cardiac contraction, has been associated with cardiac fibrillation, leading to a sudden cardiac death. A preliminary study explains that cellular alterations affect the occurrence of action potential duration (APD) alternans at slow heart rates of 400 ms by only decreasing the ryanodine receptor (RyR) inactivation rate constant (kiCa). The aim of this study is to find other cellular changes which induce the APD alternans at slow pacing rates and the effect of ion alterations on cardiac arrhythmogenesis. In the present study, we used a computational model of human atrium incorporating ionic remodeling associated with atrial fibrillation, and conducted parameter sensitivity analysis of several combinations of ionic model parameters. For evaluating alternans, we paced the human atrial tissue model with a gradual decrease cycle length (CL) subsequently, from 750 to 150 ms. As a result, the significant atrial alternans began at CL of 450 ms with decreasing the ryanodine receptor (RyR) inactivation rate constant (kiCa) by 75%, RyR sensitivity to luminal Ca2+ (ec50SR) by 50%, and sodium conductance (gNa) by 25%. In conclusion, the ionic alterations of Ca2+ and Na2+ channels contribute to produce APD alternans at slow heart rates in AF patients. This also increased arrhythmia probability in the atrial fibrillation model. Keywords: alternans, atrial fibrillation, Ca2+, Na2+, slow heart rates.