Effect of myocyte-fibroblast coupling on the onset of pathological dynamics in a model of ventricular tissue

Sridhar, S.; Vandersickel, Nele; Panfilov, Alexander V.

doi:10.1038/srep40985

Cited by 33 publications

(40 citation statements)

References 54 publications

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“…Fibroblasts contribute to the tissue structure, but experimental and computational studies have also shown that they can interact electrically with CMs when coupled. This results in alterations of the shape and the propagation of the action potential . A computational study by Zhan et al also suggests consequences for the mechanical contraction of CMs.…”

Section: Introductionmentioning

confidence: 99%

Modeling and simulation of human induced pluripotent stem cell‐derived cardiac tissue

Jung

Staat

2019

GAMM-Mitteilungen

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Human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) have become a promising in vitro model for human native cardiomyocytes. Cultivated tissue samples beat autonomously and can be used for basic and pharmacological research. For mechanical measurements of these tissue samples, the CellDrum technology has been developed. Measurements are extended by simulations with a multi‐scale electromechanically coupled finite element method based model. This model can be parameterized and validated experimentally. The paper describes the model, its workflow, and preliminary simulations to study the effect of fibroblasts and a selected cardiac drug on the electromechanics of hiPSC‐CMs.

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Section: Introductionmentioning

confidence: 99%

Modeling and simulation of human induced pluripotent stem cell‐derived cardiac tissue

Jung

Staat

2019

GAMM-Mitteilungen

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“…It can be viewed as an attempt to describe the transition from diffuse fibrosis to interstitial fibrosis 5 . As most previous modelling research dealt with diffuse fibrosis only [6][7][8][9][10][11] consideration of obstacle elongation makes, in our view, the next logical step toward more realistic fibrosis textures.…”

Section: Discussionmentioning

confidence: 99%

“…One such method is mathematical modelling. Most of modelling papers are devoted to diffuse fibrosis and study its effect on wave propagation and the onset of arrhythmia [6][7][8][9][10][11] . The effects of fibrosis texture on wave propagation have also been studied in a few papers.…”

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confidence: 99%

Anisotropic conduction in the myocardium due to fibrosis: the effect of texture on wave propagation

Nezlobinsky

Solovyova

Panfilov

2020

Sci Rep

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Cardiac fibrosis occurs in many forms of heart disease. It is well established that the spatial pattern of fibrosis, its texture, substantially affects the onset of arrhythmia. However, in most modelling studies fibrosis is represented by multiple randomly distributed short obstacles that mimic only one possible texture, diffuse fibrosis. An important characteristic feature of other fibrosis textures, such as interstitial and patchy textures, is that fibrotic inclusions have substantial length, which is suggested to have a pronounced effect on wave propagation. In this paper, we study the effect of the elongation of inexcitable inclusions (obstacles) on wave propagation in a 2D model of cardiac tissue described by the TP06 model for human ventricular cells. We study in detail how the elongation of obstacles affects various characteristics of the waves. We quantify the anisotropy induced by the textures, its dependency on the obstacle length and the effects of the texture on the shape of the propagating wave. Because such anisotropy is a result of zigzag propagation we show, for the first time, quantification of the effects of geometry and source-sink relationship, on the zigzag nature of the pathway of electrical conduction. We also study the effect of fibrosis in the case of pre-existing anisotropy and introduce a procedure for scaling of the fibrosis texture. We show that fibrosis can decrease or increase the preexisting anisotropy depending on its scaled texture.

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“…The fact that inward current reduces both AP amplitude and repolarization rate, each of which have opposite effects on APD, can explain the mixed effects that inward currents from MFBs have been found to have on APD 80 experimentally [12,17,18,53] and computationally [49,50,[54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Optogenetic currents in myofibroblasts acutely alter electrophysiology and conduction of co-cultured cardiomyocytes

Kostecki

Shi

Chen

et al. 2020

Preprint

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Interactions between cardiac myofibroblasts and myocytes may slow conduction after cardiac injury, increasing the chance of life-threatening arrhythmia. While co-culture studies have shown that myofibroblasts can affect cardiomyocyte electrophysiology in vitro, the mechanism(s) remain debatable. In this study, primary neonatal rat cardiac myofibroblasts were transduced with the light-activated ion channel Channelrhodopsin-2, which allowed acute and selective modulation of myofibroblast currents in co-cultures with cardiomyocytes. Optical mapping revealed that myofibroblast-specific optogenetically induced inward currents decreased conduction velocity in the co-cultures by 27±6% (baseline = 17.7±5.3 cm/s), and shortened the cardiac action potential duration by 14±7% (baseline = 161±11 ms) when 0.017 mW/mm 2 light was applied. When light irradiance was increased to 0.057 mW/mm 2 , the myofibroblast currents led to spontaneous beating in 6/7 co-cultures. Experiments showed that optogenetic perturbation did not lead to changes in myofibroblast strain and force generation, suggesting purely electrical effects in this model. In silico modeling of optogenetically modified myofibroblast-cardiomyocyte co-cultures largely reproduced these results and enabled a comprehensive study of relevant parameters. These results clearly demonstrate that myofibroblasts are sufficiently electrically connected to cardiomyocytes to effectively alter macroscopic electrophysiological properties in this model of cardiac tissue.

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Effect of myocyte-fibroblast coupling on the onset of pathological dynamics in a model of ventricular tissue

Cited by 33 publications

References 54 publications

Modeling and simulation of human induced pluripotent stem cell‐derived cardiac tissue

Modeling and simulation of human induced pluripotent stem cell‐derived cardiac tissue

Anisotropic conduction in the myocardium due to fibrosis: the effect of texture on wave propagation

Optogenetic currents in myofibroblasts acutely alter electrophysiology and conduction of co-cultured cardiomyocytes

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