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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

Alternans at different pacing rates. (A) Single-cell APD50 restitution curves resulting from 30 s pacing with a BCL between 0.2 and 1 s. C, K, and G models show bifurcation at short BCLs. (B) APD50 over 30 s rapid pacing with a BCL of 0.25 s. C model presents pronounced beat-to-beat alternans and G and K model produce a longer APD50 at every third beat. (C) Intracellular Ca2+ concentration between 29 and 30 s rapid pacing with a BCL of 0.25 s. Curves of N and M model calcium transient overlap. Peak of the Ca2+ transient of the C and G models visible at every second and third stimulus, respectively. K model initiates higher peak at every third stimulus, whereas N and M models cause a transient at every beat.
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Figure 3: Alternans at different pacing rates. (A) Single-cell APD50 restitution curves resulting from 30 s pacing with a BCL between 0.2 and 1 s. C, K, and G models show bifurcation at short BCLs. (B) APD50 over 30 s rapid pacing with a BCL of 0.25 s. C model presents pronounced beat-to-beat alternans and G and K model produce a longer APD50 at every third beat. (C) Intracellular Ca2+ concentration between 29 and 30 s rapid pacing with a BCL of 0.25 s. Curves of N and M model calcium transient overlap. Peak of the Ca2+ transient of the C and G models visible at every second and third stimulus, respectively. K model initiates higher peak at every third stimulus, whereas N and M models cause a transient at every beat.

Mentions: The ability of the models to represent the physiological phenomena of alternans is examined during 30 s of pacing (Figure 3). The APD50 restitution curve (Figure 3A) showed that no alternans were visible in either the N and M models, whereas the C and K models presented a bifurcation of the APD curves at a BCL of around 0.25 s and the G model already at 0.5 s. The APD50 at a BCL of 0.25 s (Figure 3B) of both the N and M models increases slightly up to 7 s of pacing, and then decreases without beat-to-beat alternans. The C model shows oscillations during the first 3 s as the model adapts to the short BCL, and then produced stable, pronounced beat-to-beat alternans of APD50. The K model presents small oscillations during the first second, and after a few seconds reverts to a nearly constant APD50. After 17 s, the APD50 of every third AP is longer than that of the others in the K model. After initial variations for 7 s, the G model also shows stable alternans with every third AP longer than the two previous beats. The peak value of the corresponding CaT (Figure 3C) is approximately 0.7–0.8 μM in the C, N, and M models and around 0.5 μM in the K and G models between 29 and 30 s of rapid pacing (BCL = 0.25 s). The C, K, and G models present higher diastolic calcium concentrations as compared to the two other models. The CaTs in the N and M models reveal a sharp peak and short duration for each stimulus. The C model results in CaTs of longer duration, sharp transitions, and a peak visible at every second stimulus. The K model shows two low-amplitude (0.4 μM) transients followed by a higher amplitude transient. In contrast, the G model shows just one long transient with a slow decrease at every third stimulus.


Benchmarking electrophysiological models of human atrial myocytes.

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

Alternans at different pacing rates. (A) Single-cell APD50 restitution curves resulting from 30 s pacing with a BCL between 0.2 and 1 s. C, K, and G models show bifurcation at short BCLs. (B) APD50 over 30 s rapid pacing with a BCL of 0.25 s. C model presents pronounced beat-to-beat alternans and G and K model produce a longer APD50 at every third beat. (C) Intracellular Ca2+ concentration between 29 and 30 s rapid pacing with a BCL of 0.25 s. Curves of N and M model calcium transient overlap. Peak of the Ca2+ transient of the C and G models visible at every second and third stimulus, respectively. K model initiates higher peak at every third stimulus, whereas N and M models cause a transient at every beat.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Alternans at different pacing rates. (A) Single-cell APD50 restitution curves resulting from 30 s pacing with a BCL between 0.2 and 1 s. C, K, and G models show bifurcation at short BCLs. (B) APD50 over 30 s rapid pacing with a BCL of 0.25 s. C model presents pronounced beat-to-beat alternans and G and K model produce a longer APD50 at every third beat. (C) Intracellular Ca2+ concentration between 29 and 30 s rapid pacing with a BCL of 0.25 s. Curves of N and M model calcium transient overlap. Peak of the Ca2+ transient of the C and G models visible at every second and third stimulus, respectively. K model initiates higher peak at every third stimulus, whereas N and M models cause a transient at every beat.
Mentions: The ability of the models to represent the physiological phenomena of alternans is examined during 30 s of pacing (Figure 3). The APD50 restitution curve (Figure 3A) showed that no alternans were visible in either the N and M models, whereas the C and K models presented a bifurcation of the APD curves at a BCL of around 0.25 s and the G model already at 0.5 s. The APD50 at a BCL of 0.25 s (Figure 3B) of both the N and M models increases slightly up to 7 s of pacing, and then decreases without beat-to-beat alternans. The C model shows oscillations during the first 3 s as the model adapts to the short BCL, and then produced stable, pronounced beat-to-beat alternans of APD50. The K model presents small oscillations during the first second, and after a few seconds reverts to a nearly constant APD50. After 17 s, the APD50 of every third AP is longer than that of the others in the K model. After initial variations for 7 s, the G model also shows stable alternans with every third AP longer than the two previous beats. The peak value of the corresponding CaT (Figure 3C) is approximately 0.7–0.8 μM in the C, N, and M models and around 0.5 μM in the K and G models between 29 and 30 s of rapid pacing (BCL = 0.25 s). The C, K, and G models present higher diastolic calcium concentrations as compared to the two other models. The CaTs in the N and M models reveal a sharp peak and short duration for each stimulus. The C model results in CaTs of longer duration, sharp transitions, and a peak visible at every second stimulus. The K model shows two low-amplitude (0.4 μM) transients followed by a higher amplitude transient. In contrast, the G model shows just one long transient with a slow decrease at every third stimulus.

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