Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice

Mayer, Andreas; Bittihn, Philip

doi:10.14814/phy2.13449

Cited by 8 publications

(4 citation statements)

References 41 publications

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“…A study of the restitution characteristics for this system, as presented in Ref. (39) (see Figures 5 A and B, therein), indicated that wave breaks occurred in a stable parameter régime, thus proving the robustness and restitutionindependence of our proposed mechanism for wave breaks.…”

Section: R a F Tsupporting

confidence: 61%

A mechanism for electric turbulence in cardiac tissue with optogenetic modification

Majumder,

Hussaini,

Zykov

et al. 2020

Preprint

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Section: R a F Tsupporting

confidence: 61%

A mechanism for electric turbulence in cardiac tissue with optogenetic modification

Majumder,

Hussaini,

Zykov

et al. 2020

Preprint

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“…APs in small tissue preparations are slightly different from those in single cardiomyocytes. Differences can arise from electrotonic coupling and the mixture of cells including fibroblasts that are able to modify the EP ( Kohl and Gourdie, 2014 ; Mayer et al, 2017 ; Hall et al, 2021 ). This can hamper the fitting of the APs and consequently, the estimation of the maximum conductances and pharmacological parameters.…”

Section: Discussionmentioning

confidence: 99%

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies

Grandits,

Augustin,

Haase

et al. 2024

eLife

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Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator enabled a massive speed-up of more than 104 compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 13.6 mV in abnormal APs exhibiting early afterdepolarizations (72% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.21 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in Vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies.

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“…First of all, this is a primary culture of animal cells, that is, a cell culture obtained by isolating cells of a certain type of tissue directly from an organ of a living organism (ex vivo) [95,96]. Cardiomyocytes cannot combine into excitable tissue after a certain period of their development.…”

Section: Application Of Different Cell Types To Simulate Cardiac Tiss...mentioning

confidence: 99%

Biomimetic Cardiac Tissue Models for In Vitro Arrhythmia Studies

Aitova,

Berezhnoy,

Tsvelaya

et al. 2023

Biomimetics

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Cardiac arrhythmias are a major cause of cardiovascular mortality worldwide. Many arrhythmias are caused by reentry, a phenomenon where excitation waves circulate in the heart. Optical mapping techniques have revealed the role of reentry in arrhythmia initiation and fibrillation transition, but the underlying biophysical mechanisms are still difficult to investigate in intact hearts. Tissue engineering models of cardiac tissue can mimic the structure and function of native cardiac tissue and enable interactive observation of reentry formation and wave propagation. This review will present various approaches to constructing cardiac tissue models for reentry studies, using the authors’ work as examples. The review will highlight the evolution of tissue engineering designs based on different substrates, cell types, and structural parameters. A new approach using polymer materials and cellular reprogramming to create biomimetic cardiac tissues will be introduced. The review will also show how computational modeling of cardiac tissue can complement experimental data and how such models can be applied in the biomimetics of cardiac tissue.

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Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice

Cited by 8 publications

References 41 publications

A mechanism for electric turbulence in cardiac tissue with optogenetic modification

A mechanism for electric turbulence in cardiac tissue with optogenetic modification

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies

Biomimetic Cardiac Tissue Models for In Vitro Arrhythmia Studies

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