A possible new cardiac heterogeneity as an arrhythmogenic driver
Abstract Atrial fibrillation (AF) is the commonest cardiac arrhythmia, affecting 3 million people in the USA and 8 million in the EU (according to the European Society of Cardiology). So, why is it that even with the best medical care, around a third of the patients are treatment resistant. Extensiv...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33438-y |
| _version_ | 1827948144242982912 |
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| author | A. Rabinovitch R. Rabinovitch Y. Biton D. Braunstein R. Thieberger |
| author_facet | A. Rabinovitch R. Rabinovitch Y. Biton D. Braunstein R. Thieberger |
| author_sort | A. Rabinovitch |
| collection | DOAJ |
| description | Abstract Atrial fibrillation (AF) is the commonest cardiac arrhythmia, affecting 3 million people in the USA and 8 million in the EU (according to the European Society of Cardiology). So, why is it that even with the best medical care, around a third of the patients are treatment resistant. Extensive research of its etiology showed that AF and its mechanisms are still debatable. Some of the AF origins are ascribed to functional and ionic heterogeneities of the heart tissue and possibly to additional triggering agents. But, have all AF origins been detected? Are all accepted origins, in fact, arrhythmogenic? In order to study these questions and specifically to check our new idea of intermittency as an arrhythmogenesis agent, we chose to employ a mathematical model which was as simple as possible, but which could still be used to observe the basic network processes of AF development. At this point we were not interested in the detailed ionic propagations nor in the actual shapes of the induced action potentials (APs) during the AF outbreaks. The model was checked by its ability to exactly recapture the basic AF developmental stages known from experimental cardiac observations and from more elaborate mathematical models. We use a simple cellular automata 2D mathematical model of N × N matrices to elucidate the field processes leading to AF in a tissue riddled with randomly distributed heterogeneities of different types, under sinus node operation, simulated by an initial line of briefly stimulated cells inducing a propagating wave, and with or without an additional active ectopic action potential pulse, in turn simulated by a transitory operation of a specific cell. Arrhythmogenic contributions, of three different types of local heterogeneities in myocytes and their collaborations, in inducing AF are examined. These are: a heterogeneity created by diffuse fibrosis, a heterogeneity created by myocytes having different refractory periods, and a new heterogeneity type, created by intermittent operation of some myocytes. The developmental stages (target waves and spirals) and the different probabilities of AF occurring under each condition, are shown. This model was established as being capable of reproducing the known AF origins and their basic development stages, and in addition has shown: (1) That diffuse fibrosis on its own is not arrhythmogenic but in combination with other arrhythmogenic agents it can either enhance or limit AF. (2) In general, combinations of heterogeneities can act synergistically, and, most importantly, (3) The new type of intermittency heterogeneity proves to be extremely arrhythmogenic. Both the intermittency risk and the fibrosis role in AF generation were established. Knowledge of the character of these arrhythmogenesis agents can be of real importance in AF treatment. |
| first_indexed | 2024-04-09T12:49:45Z |
| format | Article |
| id | doaj.art-b020d7e62bd5460fb18672dd1305382d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T12:49:45Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b020d7e62bd5460fb18672dd1305382d2023-05-14T11:17:06ZengNature PortfolioScientific Reports2045-23222023-05-0113111510.1038/s41598-023-33438-yA possible new cardiac heterogeneity as an arrhythmogenic driverA. Rabinovitch0R. Rabinovitch1Y. Biton2D. Braunstein3R. Thieberger4Physics Department, Ben-Gurion UniversityMakif YudAlefPhysics Department, Ben-Gurion UniversityPhysics Department, Sami Shamoon College of EngineeringPhysics Department, Ben-Gurion UniversityAbstract Atrial fibrillation (AF) is the commonest cardiac arrhythmia, affecting 3 million people in the USA and 8 million in the EU (according to the European Society of Cardiology). So, why is it that even with the best medical care, around a third of the patients are treatment resistant. Extensive research of its etiology showed that AF and its mechanisms are still debatable. Some of the AF origins are ascribed to functional and ionic heterogeneities of the heart tissue and possibly to additional triggering agents. But, have all AF origins been detected? Are all accepted origins, in fact, arrhythmogenic? In order to study these questions and specifically to check our new idea of intermittency as an arrhythmogenesis agent, we chose to employ a mathematical model which was as simple as possible, but which could still be used to observe the basic network processes of AF development. At this point we were not interested in the detailed ionic propagations nor in the actual shapes of the induced action potentials (APs) during the AF outbreaks. The model was checked by its ability to exactly recapture the basic AF developmental stages known from experimental cardiac observations and from more elaborate mathematical models. We use a simple cellular automata 2D mathematical model of N × N matrices to elucidate the field processes leading to AF in a tissue riddled with randomly distributed heterogeneities of different types, under sinus node operation, simulated by an initial line of briefly stimulated cells inducing a propagating wave, and with or without an additional active ectopic action potential pulse, in turn simulated by a transitory operation of a specific cell. Arrhythmogenic contributions, of three different types of local heterogeneities in myocytes and their collaborations, in inducing AF are examined. These are: a heterogeneity created by diffuse fibrosis, a heterogeneity created by myocytes having different refractory periods, and a new heterogeneity type, created by intermittent operation of some myocytes. The developmental stages (target waves and spirals) and the different probabilities of AF occurring under each condition, are shown. This model was established as being capable of reproducing the known AF origins and their basic development stages, and in addition has shown: (1) That diffuse fibrosis on its own is not arrhythmogenic but in combination with other arrhythmogenic agents it can either enhance or limit AF. (2) In general, combinations of heterogeneities can act synergistically, and, most importantly, (3) The new type of intermittency heterogeneity proves to be extremely arrhythmogenic. Both the intermittency risk and the fibrosis role in AF generation were established. Knowledge of the character of these arrhythmogenesis agents can be of real importance in AF treatment.https://doi.org/10.1038/s41598-023-33438-y |
| spellingShingle | A. Rabinovitch R. Rabinovitch Y. Biton D. Braunstein R. Thieberger A possible new cardiac heterogeneity as an arrhythmogenic driver Scientific Reports |
| title | A possible new cardiac heterogeneity as an arrhythmogenic driver |
| title_full | A possible new cardiac heterogeneity as an arrhythmogenic driver |
| title_fullStr | A possible new cardiac heterogeneity as an arrhythmogenic driver |
| title_full_unstemmed | A possible new cardiac heterogeneity as an arrhythmogenic driver |
| title_short | A possible new cardiac heterogeneity as an arrhythmogenic driver |
| title_sort | possible new cardiac heterogeneity as an arrhythmogenic driver |
| url | https://doi.org/10.1038/s41598-023-33438-y |
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