Minimal model for human ventricular action potentials in tissue

Alfonso Bueno-Orovio, Elizabeth M Cherry, Flavio H Fenton
Journal of Theoretical Biology 2008 August 7, 253 (3): 544-60
Modeling the dynamics of wave propagation in human ventricular tissue and studying wave stability require models that reproduce realistic characteristics in tissue. We present a minimal ventricular (MV) human model that is designed to reproduce important tissue-level characteristics of epicardial, endocardial and midmyocardial cells, including action potential (AP) amplitudes and morphologies, upstroke velocities, steady-state action potential duration (APD) and conduction velocity (CV) restitution curves, minimum APD, and minimum diastolic interval. The model is then compared with three previously published human ventricular cell models, the Priebe and Beuckelmann (PB), the Ten Tusscher-Noble-Noble-Panfilov (TNNP), and the Iyer-Mazhari-Winslow (IMW). For the first time, the stability of reentrant waves for all four models is analyzed, and quantitative comparisons are made among the models in single cells and in tissue. The PB, TNNP, and IMW models exhibit quantitative differences in APD and CV rate adaptation, as well as completely different reentrant wave dynamics of quasi-breakup, stability, and breakup, respectively. All the models have dominant frequencies comparable to clinical values except for the IMW model, which has a large range of frequencies extending beyond the clinical range for both ventricular tachycardia (VT) and ventricular fibrillation (VF). The TNNP and IMW models possess a large degree of short-term memory and we show for the first time the existence of memory in CV restitution. The MV model also can be fitted to reproduce the dynamics of other models and is computationally more efficient: the times required to simulate the MV, TNNP, PB and IMW models follow the ratio 1:31:50:8084.

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