Table 2.
Overview of modifications to the main human ventricular cardiomyocyte models
| Model | Innovation from Original Model and Purpose |
|---|---|
| Original model: O’Hara–Rudy 2011 (67) | |
| Bartolucci 2020 (150) | Capture the inverse dependence of APD on extracellular Ca2+ and APD rate dependence at 4 mM extracellular K+Changes to: • sensitivity of Ca2+-dependent inactivation of ICaL • reparameterization of calcium handling parameters |
| Gando 2020 (151) | Replacement of fast and late Na+ current by Markov model (152) |
| Passini 2016 (153) | Improve reproduction of experimental data through: • Ito increase • extracellular concentrations set as experiments • modified K+ equilibrium potential • modified INa steady state inactivation • modified current stimulus |
| Tomek 2020 (73) | • Improve behavior of O’Hara–Rudy 2011 (67) for AP plateau, APD accommodation in response to heart rate acceleration, INa block. Main changes: reevaluation of ICaL and IKr • Explicit validation of drug effects with an independent experimental dataset |
| Lee 2017 (154) | • Addition of the Heijman (41) beta-adrenergic stimulation model • IKs formulation modified to account for Ca2+ dependence of IKs (Markov IKs) |
| Whittaker 2017 (155) | • Modified INa formulation [from Luo–Rudy (34)] • Markov formulation of IKr |
| Li 2017 (CiPA) (156) | Dynamic hERG drug-binding model for IKr |
| Dutta 2017 (157) (CiPA) | Scaling of IKr, IKs, IK1, ICaL, INaL to fit published APD rate dependence experimental data and response to drug block [based on Li 2017 (156)] |
| Romero 2015 (158) | Markov formulation of IKr based on Fink 2008 (159) |
| Trenor 2013 (160) | New formulation of INaL (conductance fitted to experimental data) |
| Original model: Grandi (147) | |
| Carro 2011 (161) | • Reformulating of ICaL [fast and slow inactivation gate as in ten Tusscher (144)] and IK1 • Redefinition of INa and INaK to improve APD restitution curve shape, slope, and APD response to heart rate changes |
| Trenor 2012 (162) | New formulation of INaL [based on ten Tusscher (144)], in the setting of heart failure |
| Asakura 2014 (163) | Inclusion of calcium-induced calcium release as in Hinch model of CaRU: local control of RyR by L-type calcium channel |
| Original model: ten Tusscher (144) | |
| Xia 2006 (164) | • Inclusion of INaL, vmax • Modification of INaCa, Ito, IKs based on recent human experimental data |
| ten Tusscher 2006 (165) | Reduced model to improve computational efficiency [like Bernus (166)] |
| Grandi 2009 (167) | New formulations of the Ca2+ dependence of IKs, IKr, and ICaL to capture APD dependence on extracellular calcium |
| Fink 2008 (159) | Updated K+ currents: IK1 (accounting for the blocking effects of intracellular magnesium and spermidine on this potassium conductance), IKr (Markov model) |
| Adeniran 2017 (168) | Markov model for IKs |
| Original model: Bueno-Orovio (77) | |
| Kienast 2017 (169) | Effect of temperature (cooling-induced effect on AP) |
| Bueno Orovio 2012 (170) | Capture APD adaptation dynamics (by adaptation of model parameters) |
| Original model: Priebe and Beuckelmann (149) | |
| Bernus 2002 (166) | Reformulation to be computationally efficient (2-D), 6-variable model |
AP, action potential; APD, AP duration; CiPA, Comprehensive in vitro Proarrhythmia Assay; 2-D, 2-dimensional; CaRU, Ca2+ release unit; ICa,L, L-type Ca2+ current; IK1, basal inward-rectifier K+ current; IKr, rapid delayed-rectifier K+ current; IKs, slow delayed-rectifier K+ current; INa, Na+ current; INa,L, L-type Na+ current; Ito, transient outward K+ current; RyR, ryanodine receptor.