Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model
During cardiac diseases many types of anatomical and functional remodeling of cardiac tissue can occur. In this work, we focus on two conditions: hypoxia and fibrosis, which are part of complex pathological modifications that take place in many cardiac diseases (hypertrophic cardiomyopathy, hyperten...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.00764/full |
| _version_ | 1811268825753059328 |
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| author | Rafael Sachetto Rafael Sachetto Sergio Alonso Sergio Alonso Rodrigo Weber dos Santos |
| author_facet | Rafael Sachetto Rafael Sachetto Sergio Alonso Sergio Alonso Rodrigo Weber dos Santos |
| author_sort | Rafael Sachetto |
| collection | DOAJ |
| description | During cardiac diseases many types of anatomical and functional remodeling of cardiac tissue can occur. In this work, we focus on two conditions: hypoxia and fibrosis, which are part of complex pathological modifications that take place in many cardiac diseases (hypertrophic cardiomyopathy, hypertensive heart disease, and recurrent myocardial infarction) and respiratory diseases (obstructive pulmonary disease, obstructive sleep apnea, and cystic fibrosis). Using computational models of cardiac electrophysiology, we evaluate if the interplay between hypoxia and fibrosis is sufficient to trigger cardiac arrhythmia. We study the mechanisms behind the generation of ectopic beats, an arrhythmic trigger also known as premature ventricular contractions (PVCs), in regions with high hypoxia and fibrosis. First, we modify an electrophysiological model of myocytes of the human left ventricle to include the effects of hypoxia. Second, diffuse fibrosis is modeled by randomly replacing cardiac myocytes by non-excitable and non-conducting cells. The Monte Carlo method is used to evaluate the probability of a region to generate ectopic beats with respect to different levels of hypoxia and fibrosis. In addition, we evaluate the minimum size of three-dimensional slabs needed to sustain reentries for different stimulation protocols. The observed mechanism behind the initiation of ectopic beats is unidirectional block, giving rise to sustained micro-reentries inside the region with diffuse fibrosis and hypoxia. In summary, our results suggest that hypoxia and fibrosis are sufficient for the creation of a focal region in the heart that generates PVCs. |
| first_indexed | 2024-04-12T21:29:53Z |
| format | Article |
| id | doaj.art-33915a2a0bfa4acebe815a9273c43cd0 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T21:29:53Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-33915a2a0bfa4acebe815a9273c43cd02022-12-22T03:16:03ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-06-01910.3389/fphys.2018.00764351318Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular ModelRafael Sachetto0Rafael Sachetto1Sergio Alonso2Sergio Alonso3Rodrigo Weber dos Santos4Department of Computer Science, Universidade Federal de São João del-Rei, São João del-Rei, BrazilGraduate Program in Computational Modeling, Universidade Federal de Juiz de Fora, Juiz de Fora, BrazilGraduate Program in Computational Modeling, Universidade Federal de Juiz de Fora, Juiz de Fora, BrazilDepartment of Physics, Universitat Politècnica de Catalunya, Barcelona, SpainGraduate Program in Computational Modeling, Universidade Federal de Juiz de Fora, Juiz de Fora, BrazilDuring cardiac diseases many types of anatomical and functional remodeling of cardiac tissue can occur. In this work, we focus on two conditions: hypoxia and fibrosis, which are part of complex pathological modifications that take place in many cardiac diseases (hypertrophic cardiomyopathy, hypertensive heart disease, and recurrent myocardial infarction) and respiratory diseases (obstructive pulmonary disease, obstructive sleep apnea, and cystic fibrosis). Using computational models of cardiac electrophysiology, we evaluate if the interplay between hypoxia and fibrosis is sufficient to trigger cardiac arrhythmia. We study the mechanisms behind the generation of ectopic beats, an arrhythmic trigger also known as premature ventricular contractions (PVCs), in regions with high hypoxia and fibrosis. First, we modify an electrophysiological model of myocytes of the human left ventricle to include the effects of hypoxia. Second, diffuse fibrosis is modeled by randomly replacing cardiac myocytes by non-excitable and non-conducting cells. The Monte Carlo method is used to evaluate the probability of a region to generate ectopic beats with respect to different levels of hypoxia and fibrosis. In addition, we evaluate the minimum size of three-dimensional slabs needed to sustain reentries for different stimulation protocols. The observed mechanism behind the initiation of ectopic beats is unidirectional block, giving rise to sustained micro-reentries inside the region with diffuse fibrosis and hypoxia. In summary, our results suggest that hypoxia and fibrosis are sufficient for the creation of a focal region in the heart that generates PVCs.https://www.frontiersin.org/article/10.3389/fphys.2018.00764/fullectopic beatsfibrosishypoxiacardiac electrophysiologyheart simulationspercolation threshold |
| spellingShingle | Rafael Sachetto Rafael Sachetto Sergio Alonso Sergio Alonso Rodrigo Weber dos Santos Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model Frontiers in Physiology ectopic beats fibrosis hypoxia cardiac electrophysiology heart simulations percolation threshold |
| title | Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model |
| title_full | Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model |
| title_fullStr | Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model |
| title_full_unstemmed | Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model |
| title_short | Killing Many Birds With Two Stones: Hypoxia and Fibrosis Can Generate Ectopic Beats in a Human Ventricular Model |
| title_sort | killing many birds with two stones hypoxia and fibrosis can generate ectopic beats in a human ventricular model |
| topic | ectopic beats fibrosis hypoxia cardiac electrophysiology heart simulations percolation threshold |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.00764/full |
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