Evaluating computational efforts and physiological resolution of mathematical models of cardiac tissue

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 23, 2024

Computational techniques have significantly advanced our understanding of cardiac electrophysiology, yet they predominantly concentrated on averaged models that do not represent the intricate dynamics near individual cardiomyocytes. Recently, accurate representing cells gained popularity, enabling analysis electrophysiology at micrometer level. Here, we evaluate five mathematical to determine their computational efficiency and physiological fidelity. Our findings reveal cell-based introduced in recent literature offer both precision for simulating small tissue samples (comprising thousands cardiomyocytes). Conversely, traditional bidomain model its simplified counterpart, monodomain model, are more appropriate larger masses (encompassing millions billions For simulations requiring detailed parameter variations along cell membranes, EMI emerges as only viable choice. This distinctively accounts extracellular (E), membrane (M), intracellular (I) spaces, providing a comprehensive framework studies. Nonetheless, model's applicability large-scale tissues is limited by substantial demands subcellular resolution.

Language: Английский

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Efficient, cell-based simulations of cardiac electrophysiology; The Kirchhoff Network Model (KNM)

npj Systems Biology and Applications, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 14, 2023

Mathematical models based on homogenized representation of cardiac tissue have greatly improved our understanding electrophysiology. However, these are too coarse to investigate the dynamics at level myocytes since cells not present in models. Recently, fine scale been proposed allow for cell-level resolution dynamics, but computationally expensive be used applications like whole heart simulations large animals. To address this issue, we propose a model that balances computational demands and physiological accuracy. The is founded Kirchhoff's current law, represents every myocyte tissue. This allows specific properties assigned individual cardiomyocytes, other cell types fibroblasts can added an accurate manner while keeping computing efforts reasonable.

Language: Английский

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A possible path to persistent re-entry waves at the outlet of the left pulmonary vein

npj Systems Biology and Applications, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 23, 2024

Abstract Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, often evolving from paroxysmal episodes to persistent stages over an extended timeframe. While various factors contribute this progression, precise biophysical mechanisms driving it remain unclear. Here we explore how rapid firing cardiomyocytes at outlet pulmonary vein left atria can create a substrate for re-entry wave. This grounded in recently formulated mathematical model regulation calcium ion channel density by intracellular concentration. According model, number channels controlled In particular, if concentration increases above certain target level, current weakened restore level calcium. During pacing, leading substantial reduction across membrane myocytes, which again reduces action potential duration. spatially resolved cell-based atria, show that reduced duration lead re-entry. Initiated stemming AF lasting several days, critical factor. Our findings illustrate such foster conducive environment through electrical remodeling, characterized diminished currents. underscores importance promptly addressing early prevent their progression chronic stages.

Language: Английский

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Boundary integral formulation of the cell-by-cell model of cardiac electrophysiology

Engineering Analysis with Boundary Elements, Journal Year: 2023, Volume and Issue: 158, P. 239 - 251

Published: Nov. 3, 2023

We propose a boundary element method for the accurate solution of cell-by-cell bidomain model electrophysiology. The model, also called Extracellular-Membrane-Intracellular (EMI) is system reaction–diffusion equations describing evolution electric potential within each domain: intra- and extra-cellular space cellular membrane. parabolic but degenerate because time derivative only in membrane domain. In this work, we adopt boundary-integral formulation removing degeneracy recast it to equation on numerically advantageous since number degrees freedom sensibly reduced compared original model. Specifically, prove that boundary-element discretization EMI equivalent ordinary differential equations, consider based multirate explicit stabilized Runge–Kutta method. show our scheme convergences exponentially single-cell case. finally provide several numerical experiments biological interest.

Language: Английский

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Scalable Approximation and Solvers for Ionic Electrodiffusion in Cellular Geometries

SIAM Journal on Scientific Computing, Journal Year: 2024, Volume and Issue: 46(5), P. B725 - B751

Published: Oct. 16, 2024

Language: Английский

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Determining properties of human‐induced pluripotent stem cell‐derived cardiomyocytes using spatially resolved electromechanical metrics

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) are increasingly important in preclinical drug assessments, particularly for identifying potential cardiotoxicity. In this study, we utilize data from microphysiological systems of hiPSC‐CMs to evaluate cellular characteristics, such as action duration, beat rate, conduction velocity and mechanical displacement. Based on these data, high‐fidelity mathematical models facilitate precise assessments critical biophysical parameters the cells, including membrane ion channel conductances, cross‐bridge cycle transition rates cell‐to‐cell conductance. We emphasize distinction between synchronized transients travelling waves, highlighting their implications deducing properties hiPSC‐CMs. analyse effects compounds flecainide, quinidine, nifedipine, verapamil, blebbistatin omecamtiv. Our findings show that drug‐induced changes describing currents contractile machinery close ranges reported literature, computed biomarkers align well with measured biomarkers. This study is first apply spatially resolved, cell‐based identify through measurements transmembrane displacement, marking a significant step forward using computational evaluating safety offering new approach early identification adverse reactions. image Key points Optical human‐induced present opportunities advance understanding how human heart cells function interact. Although direct optical yield valuable biomarkers, they fall short revealing underlying properties, example, novel perturb channels. Drug best understood capture cell dynamics based physical laws. Traditionally, have been averaged over all collections, thus overlooking spatiotemporal waves. Here, use recently developed models, representing spatial electrical coupling, determine collections

Language: Английский

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The simplified Kirchhoff network model (SKNM): a cell-based reaction–diffusion model of excitable tissue

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 30, 2023

Abstract Cell-based models of excitable tissues offer the advantage cell-level precision, which cannot be achieved using traditional homogenized electrophysiological models. However, this enhanced accuracy comes at cost increased computational demands, necessitating development efficient cell-based The widely-accepted bidomain model serves as standard in cardiac electrophysiology, and under certain anisotropy ratio conditions, it is well known that can reduced to simpler monodomain model. Recently, Kirchhoff Network Model (KNM) was developed a counterpart In paper, we aim demonstrate KNM simplified same steps employed derive from We present Simplified (SKNM), produces results closely aligned with those while requiring significantly less resources.

Language: Английский

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Cardiac computed tomography angiography-derived pulmonary vein volumetry as a predictor for atrial fibrillation recurrence after catheter ablation

Quantitative Imaging in Medicine and Surgery, Journal Year: 2024, Volume and Issue: 14(3), P. 2213 - 2224

Published: March 1, 2024

Background: There is an increasing evidence that pulmonary vein (PV) enlargement associated with atrial fibrillation (AF); however, the predictive value of PV in AF recurrence remains unclear. This study sought to evaluate whether volume quantification derived from cardiac computed tomographic angiography (CCTA) could serve as a indicator success catheter ablation (CA) procedure.

Language: Английский

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Computational Modeling of Sodium-Ion-Channel-Based Glucose Sensing Biophysics to Study Cardiac Pacemaker Action Potential

Mathematical and Computational Applications, Journal Year: 2024, Volume and Issue: 29(5), P. 84 - 84

Published: Sept. 21, 2024

Elevated blood glucose levels, known as hyperglycemia, play a significant role in sudden cardiac arrest, often resulting death, particularly among those with diabetes. Understanding the internal mechanisms has been challenge for healthcare professionals, leading many research groups to investigate relationship between levels and electrical activity. Our hypothesis suggests that glucose-sensing biophysics tissue could clarify this connection. To explore this, we adapted single-compartment computational model of human pacemaker action potential. We incorporated voltage-gated sodium ion channels using ordinary differential equations. Parameters were based on existing experimental studies mimic impact potential firing. Simulations voltage clamp current techniques showed elevated decreased channel currents, reduction frequency. In summary, our mathematical provides cellular-level understanding how high can lead bradycardia death.

Language: Английский

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Re-Introducing the Cell: The Extracellular-Membrane-Intracellular (EMI) Model

Simula SpringerBriefs on computing, Journal Year: 2023, Volume and Issue: unknown, P. 107 - 117

Published: Jan. 1, 2023

Abstract As mentioned earlier, the bidomain system is currently standard mathematical model of cardiac electrophysiology. This nowroutinely solved and provides valuable insights into conduction electrical signals in tissue. However, has one glaring limitation: The cardiomyocyte nowhere to be found model, since extracellular space, intracellular space cell membrane are all assumed everywhere computational domain. was lost homogenization! There a tremendous advantage this because becomes much simpler thus solvable for whole human heart. And it works! But downside course that essential building block tissue leaving out consequences. For instance, impossible investigate detailed dynamics electrochemical processes vicinity small collection cells.

Language: Английский

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