2021
DOI: 10.3389/fphys.2021.763584
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From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology

Abstract: Computational modeling has contributed significantly to present understanding of cardiac electrophysiology including cardiac conduction, excitation-contraction coupling, and the effects and side-effects of drugs. However, the accuracy of in silico analysis of electrochemical wave dynamics in cardiac tissue is limited by the homogenization procedure (spatial averaging) intrinsic to standard continuum models of conduction. Averaged models cannot resolve the intricate dynamics in the vicinity of individual cardio… Show more

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Cited by 21 publications
(33 citation statements)
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References 45 publications
(47 reference statements)
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“…The second limitation is that convergence is obtained using a relatively coarse mesh ( x ∼ 0.25 mm, see Xie et al, 2004;Clayton and Panfilov, 2008;Niederer et al, 2011b) and thus a typical mesh block contains several hundred cardiomyocytes (see, e.g., Jaeger et al, 2021a,b). Therefore, understanding of the conduction properties (see, e.g., Henriquez, 2014;Veeraraghavan et al, 2014) close to the myocytes cannot be achieved using these models (see, e.g., Jaeger et al, 2021a).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…The second limitation is that convergence is obtained using a relatively coarse mesh ( x ∼ 0.25 mm, see Xie et al, 2004;Clayton and Panfilov, 2008;Niederer et al, 2011b) and thus a typical mesh block contains several hundred cardiomyocytes (see, e.g., Jaeger et al, 2021a,b). Therefore, understanding of the conduction properties (see, e.g., Henriquez, 2014;Veeraraghavan et al, 2014) close to the myocytes cannot be achieved using these models (see, e.g., Jaeger et al, 2021a).…”
Section: Introductionmentioning
confidence: 99%
“…These limitations of the homogenized (bidomain/monodomain) models are well known and several authors have developed alternatives where all individual cells are explicitly represented in the models (see, e.g., Spach et al, 2007;Jacquemet and Henriquez, 2009;Hubbard and Henriquez, 2014;Lin and Keener, 2014;Tveito et al, 2017a;Weinberg, 2017;Jaeger et al, 2019Jaeger et al, , 2021aDomínguez et al, 2021;Jaeger and Tveito, 2021). Here, we will apply the EMI model where both the extracellular space (E), the cell membrane (M) and the intracellular space (I) are explicitly represented in the model (see, e.g., Tveito et al, 2017a,b;Jaeger and Tveito, 2021), and compare properties with the homogenized bidomain model.…”
Section: Introductionmentioning
confidence: 99%
“…Still, this problem represents a substantial computational effort. To date, very large cardiac simulations involving both classical and more recent electrodiffusion models ( Tveito et al, 2017 ; Jæger et al, 2021a ) have been performed at a similar scale (several billion computational nodes), albeit using powerful compute resources and for very brief simulation times ( Jæger et al, 2021b ). As such, approaching this computational problem is likely to require similarly substantial computational resources, thoroughly optimized numerical implementations, and well-designed simulations of relatively short duration.…”
Section: The Coming Challenges Of Interdisciplinary Design In Studyin...mentioning
confidence: 99%
“…The storied work of Hodgkin and Huxley (1952a , b , c , d) and Hodgkin et al (1952) gave every reason for optimism, and the same methods were quickly applied to understand cardiac electrical activation ( Noble, 1962 ). From these formalisms, continuum mathematical representations were developed to understand many aspects of macroscopic cardiac function ( Plonsey and Barr, 1987 ; Henriquez, 1993 , 2014 ; Henriquez et al, 2004 ; Roberts et al, 2008 ; Tveito et al, 2017 ; Jæger et al, 2021a ). As many of the imaging methods described above have developed, it has become apparent that nanometer scale structures and their functional dynamics make critical contributions to cardiac electrophysiology and contractile function.…”
Section: The Coming Challenges Of Interdisciplinary Design In Studyin...mentioning
confidence: 99%
“…We then let the model approach a resting state by letting only the K + channels be open between the intracellular and extracellular spaces on the membrane of both cells. For the initial conditions (electroneutral), ρ is zero, and φ is constant (see (6) and ( 10)).…”
Section: Simulation Setupmentioning
confidence: 99%