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Benchmarking electrophysiological models of human atrial myocytes.

Wilhelms M, Hettmann H, Maleckar MM, Koivumäki JT, Dössel O, Seemann G - Front Physiol (2013)

Bottom Line: The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations.Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans.The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Engineering, Karlsruhe Institute of Technology Karlsruhe, Germany.

ABSTRACT
Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation (AF). In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans. To assess the models' ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation (cAF) was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits.

No MeSH data available.


Related in: MedlinePlus

(A–E) Control and cAF APs of the five models. AP shape is triangular in C, N, M, and K models in case of cAF and APD duration is shortened in all models.
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Figure 4: (A–E) Control and cAF APs of the five models. AP shape is triangular in C, N, M, and K models in case of cAF and APD duration is shortened in all models.

Mentions: For the comparison of control and cAF APs, the models were modified to reproduce effects of electrical remodeling (changes outlined in section 2). Figure 4 shows the resulting APs of the five models. Figures 4A–E present a single AP of each model, following 50 s of pacing (at a BCL of 1 s). In the C, N, M, and K models, AP morphology appears triangulated in the cAF case, independent of the shape of the control AP. The G model reveals biphasic repolarization in the control as well as in the cAF case. Furthermore, upstroke velocity is increased in the G model in case of cAF and a pronounced overshoot can be observed. Table 2 presents the resulting AP amplitude, RMP, APD90, and dV/dtmax of the modified cAF models, which can be compared to measured values shown in Table 3. Only the C model produces an amplitude in the range of experimental data of Bosch et al. (1999), whereas the amplitude of the other models is 10–15 mV higher. The RMPs of the N, M, K, and G models are similar and lie in the range of experimental data, whereas the C model shows an increased RMP. The APD50 of the C model is between 35 and 45 ms longer than that of the other models. Similarly, the APD90 of the C model is also longest of all models but is shorter than the experimental values of Christ et al. (2008). The N, M, K, and G models better fit to the measurements of Bosch et al. (1999) and Workman et al. (2001). The upstroke velocity dV/dtmax of the N, M, and K models are similar, but lower than that of the C model, which fits best the experimental value of Workman et al. (2001). The G model has a more than 150 V/s faster upstroke velocity than the other models. The maximum current amplitudes of the different models during control sinus rhythm and cAF can be found in Table 4. For better comparison of the current amplitudes among the different models, they were normalized to the value of IK1 after 50 s clamped to a transmembrane voltage of −75 mV.


Benchmarking electrophysiological models of human atrial myocytes.

Wilhelms M, Hettmann H, Maleckar MM, Koivumäki JT, Dössel O, Seemann G - Front Physiol (2013)

(A–E) Control and cAF APs of the five models. AP shape is triangular in C, N, M, and K models in case of cAF and APD duration is shortened in all models.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539682&req=5

Figure 4: (A–E) Control and cAF APs of the five models. AP shape is triangular in C, N, M, and K models in case of cAF and APD duration is shortened in all models.
Mentions: For the comparison of control and cAF APs, the models were modified to reproduce effects of electrical remodeling (changes outlined in section 2). Figure 4 shows the resulting APs of the five models. Figures 4A–E present a single AP of each model, following 50 s of pacing (at a BCL of 1 s). In the C, N, M, and K models, AP morphology appears triangulated in the cAF case, independent of the shape of the control AP. The G model reveals biphasic repolarization in the control as well as in the cAF case. Furthermore, upstroke velocity is increased in the G model in case of cAF and a pronounced overshoot can be observed. Table 2 presents the resulting AP amplitude, RMP, APD90, and dV/dtmax of the modified cAF models, which can be compared to measured values shown in Table 3. Only the C model produces an amplitude in the range of experimental data of Bosch et al. (1999), whereas the amplitude of the other models is 10–15 mV higher. The RMPs of the N, M, K, and G models are similar and lie in the range of experimental data, whereas the C model shows an increased RMP. The APD50 of the C model is between 35 and 45 ms longer than that of the other models. Similarly, the APD90 of the C model is also longest of all models but is shorter than the experimental values of Christ et al. (2008). The N, M, K, and G models better fit to the measurements of Bosch et al. (1999) and Workman et al. (2001). The upstroke velocity dV/dtmax of the N, M, and K models are similar, but lower than that of the C model, which fits best the experimental value of Workman et al. (2001). The G model has a more than 150 V/s faster upstroke velocity than the other models. The maximum current amplitudes of the different models during control sinus rhythm and cAF can be found in Table 4. For better comparison of the current amplitudes among the different models, they were normalized to the value of IK1 after 50 s clamped to a transmembrane voltage of −75 mV.

Bottom Line: The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations.Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans.The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Engineering, Karlsruhe Institute of Technology Karlsruhe, Germany.

ABSTRACT
Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation (AF). In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans. To assess the models' ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation (cAF) was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits.

No MeSH data available.


Related in: MedlinePlus