The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Atrial Myocyte under Atrial Fibrillation Remodeling
2.2. Fibroblast, Myofibroblast and Fibrocyte Model
2.3. Diffuse Fibrosis in a 3D Model of Human Atria
2.4. Model of Electrical Propagation
2.5. Stimulation Protocol and Simulation Setup
2.6. Electrograms and Dominant Frequency
3. Results
3.1. Conduction Velocity and Action Potential Duration
3.2. Propagation Dynamics during AF without Fibrosis
3.3. Propagation Dynamics in the Right Atrium during AF with Fibrosis
3.4. Propagation Dynamics in the Left Atrium during AF with Fibrosis
3.5. Electrograms and DF Analysis
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell | Capacitance | Conductivity | References |
---|---|---|---|
Cardiomyocyte | 100 pF | 0.26 S/cm | [38,51] |
Fibroblast | 6.3 pF | 0.078 S/cm | [45,46,47,49] |
Myofibroblast | 50.4 pF | 0.078 S/cm | [46,49] |
Fibrocyte | 6.3 pF | 0.024 S/cm | [36,46,47,50,52] |
Fibrosis Configuration | APD90 (ms) | APD90 Reduction | CV (cm/s) | CV Reduction | ||||
---|---|---|---|---|---|---|---|---|
Low Density | High Density | Low Density | High Density | Low Density | High Density | Low Density | High Density | |
Without fibrosis | 118 | - | 62 | - | ||||
Fibroblasts | 112 | 104 | 5% | 12% | 33 | 18 | 47% | 71% |
Myofibroblasts | 116 | 104 | 2% | 12% | 49 | 58 | 21% | 6% |
Fibrocytes | 114 | 94 | 3% | 20% | 24 | 11 | 61% | 82% |
Fibroblasts + myofibroblasts | 114 | 105 | 3% | 11% | 35 | 27 | 44% | 56% |
Fibroblasts + fibrocytes | 113 | 104 | 4% | 12% | 32 | 13 | 49% | 79% |
Myofibroblasts + fibrocytes | 114 | 105 | 3% | 11% | 42 | 19 | 32% | 70% |
Fibroblasts + myofibroblasts + fibrocytes | 113 | 105 | 4% | 11% | 36 | 19 | 42% | 70% |
Fibrosis Configuration | Fibrosis Density | LA mDF (Hz) | RA mDF (Hz) | Right-to-Left DF Gradient (Hz) |
---|---|---|---|---|
Without fibrosis | - | 9.2 | 9.2 | 0.0 |
Fibroblasts | Low | 8.8 | 9.2 | 0.4 |
High | 6.7 | 9.3 | 2.6 | |
Myofibroblasts | Low | 8.9 | 9.3 | 0.4 |
High | 8.3 | 9.3 | 1.0 | |
Fibrocytes | Low | 8.3 | 9.3 | 1.0 |
High | 4.8 | 9.3 | 4.5 | |
Fibroblasts + myofibroblasts | Low | 9.1 | 9.3 | 0.2 |
High | 7.5 | 9.3 | 1.8 | |
Fibrocytes + fibroblasts | Low | 8.7 | 9.2 | 0.5 |
High | 5.5 | 9.2 | 3.7 | |
Fibrocytes + myofibroblasts | Low | 8.4 | 9.3 | 0.9 |
High | 7.0 | 9.3 | 2.3 | |
Fibrocytes + myofibroblasts + fibrocytes | Low | 8.7 | 9.3 | 0.6 |
High | 6.8 | 9.3 | 2.5 |
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Palacio, L.C.; Ugarte, J.P.; Saiz, J.; Tobón, C. The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study. Cells 2021, 10, 2769. https://doi.org/10.3390/cells10102769
Palacio LC, Ugarte JP, Saiz J, Tobón C. The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study. Cells. 2021; 10(10):2769. https://doi.org/10.3390/cells10102769
Chicago/Turabian StylePalacio, Laura C., Juan P. Ugarte, Javier Saiz, and Catalina Tobón. 2021. "The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study" Cells 10, no. 10: 2769. https://doi.org/10.3390/cells10102769