The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study
Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunct...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2769 |
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| author | Laura C. Palacio Juan P. Ugarte Javier Saiz Catalina Tobón |
| author_facet | Laura C. Palacio Juan P. Ugarte Javier Saiz Catalina Tobón |
| author_sort | Laura C. Palacio |
| collection | DOAJ |
| description | Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF. |
| first_indexed | 2024-03-10T06:39:35Z |
| format | Article |
| id | doaj.art-7d6b45adc39f48329ebb0e43b3c84c2a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:35Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7d6b45adc39f48329ebb0e43b3c84c2a2023-11-22T17:48:53ZengMDPI AGCells2073-44092021-10-011010276910.3390/cells10102769The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico StudyLaura C. Palacio0Juan P. Ugarte1Javier Saiz2Catalina Tobón3Materiales Nanoestructurados y Biomodelación (MATBIOM), Universidad de Medellín, Medellín 050032, ColombiaGrupo de Investigación en Modelamiento y Simulación Computacional (GIMSC), Universidad de San Buenaventura, Medellín 050010, ColombiaCentro de Investigación e Innovación en Bioingeniería (CI<sup>2</sup>B), Universitat Politècnica de València, 46022 Valencia, SpainMateriales Nanoestructurados y Biomodelación (MATBIOM), Universidad de Medellín, Medellín 050032, ColombiaRemodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.https://www.mdpi.com/2073-4409/10/10/2769diffuse fibrosisatrial fibrillation3D modelselectrograms |
| spellingShingle | Laura C. Palacio Juan P. Ugarte Javier Saiz Catalina Tobón The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study Cells diffuse fibrosis atrial fibrillation 3D models electrograms |
| title | The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study |
| title_full | The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study |
| title_fullStr | The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study |
| title_full_unstemmed | The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study |
| title_short | The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study |
| title_sort | effects of fibrotic cell type and its density on atrial fibrillation dynamics an in silico study |
| topic | diffuse fibrosis atrial fibrillation 3D models electrograms |
| url | https://www.mdpi.com/2073-4409/10/10/2769 |
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