Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria
Background: Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet t...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/3/746 |
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| author | Barbara C. Niort Alice Recalde Caroline Cros Fabien Brette |
| author_facet | Barbara C. Niort Alice Recalde Caroline Cros Fabien Brette |
| author_sort | Barbara C. Niort |
| collection | DOAJ |
| description | Background: Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet to date, there is no information that maps calcium signaling across the left atrium. Objective: The aim of this study is to determine whether calcium signaling is homogenous throughout the different regions of the left atrium. This work tests the hypothesis that differences across the healthy left atrium contribute to a unique, region-dependent calcium cycling and participates in the pro-arrhythmic activity during atrial fibrillation. Methods: An animal model relevant to human cardiac function (the sheep) was used to characterize both the electrical activity and the calcium signaling of three distinct left atrium regions (appendage, free wall and pulmonary veins) in control conditions and after acetylcholine perfusion (5 μM) to induce acute atrial fibrillation. High-resolution dual calcium-voltage optical mapping on the left atria of sheep was performed to explore the spatiotemporal dynamics of calcium signaling in relation to electrophysiological properties. Results: Action potential duration (at 80% repolarization) was not significantly different in the three regions of interest for the three pacing sites. In contrast, the time to 50% calcium transient decay was significantly different depending on the region paced and recorded. Acetylcholine perfusion and burst pacing-induced atrial fibrillation when pulmonary veins and appendage regions were paced but not when the free wall region was. Dantrolene (a ryanodine receptor blocker) did not reduce atrial fibrillation susceptibility. Conclusion: These data provide the first evidence of heterogenous calcium signaling across the healthy left atrium. Such basal regional differences may be exacerbated during the progression of atrial fibrillation and thus play a crucial role in focal arrhythmia initiation without ryanodine receptor gating modification. |
| first_indexed | 2024-03-11T09:38:34Z |
| format | Article |
| id | doaj.art-139912d251394a59bfd353a069d314fd |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T09:38:34Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-139912d251394a59bfd353a069d314fd2023-11-16T17:06:36ZengMDPI AGJournal of Clinical Medicine2077-03832023-01-0112374610.3390/jcm12030746Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left AtriaBarbara C. Niort0Alice Recalde1Caroline Cros2Fabien Brette3Centre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, FranceCentre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, FranceCentre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, FranceCentre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, FranceBackground: Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet to date, there is no information that maps calcium signaling across the left atrium. Objective: The aim of this study is to determine whether calcium signaling is homogenous throughout the different regions of the left atrium. This work tests the hypothesis that differences across the healthy left atrium contribute to a unique, region-dependent calcium cycling and participates in the pro-arrhythmic activity during atrial fibrillation. Methods: An animal model relevant to human cardiac function (the sheep) was used to characterize both the electrical activity and the calcium signaling of three distinct left atrium regions (appendage, free wall and pulmonary veins) in control conditions and after acetylcholine perfusion (5 μM) to induce acute atrial fibrillation. High-resolution dual calcium-voltage optical mapping on the left atria of sheep was performed to explore the spatiotemporal dynamics of calcium signaling in relation to electrophysiological properties. Results: Action potential duration (at 80% repolarization) was not significantly different in the three regions of interest for the three pacing sites. In contrast, the time to 50% calcium transient decay was significantly different depending on the region paced and recorded. Acetylcholine perfusion and burst pacing-induced atrial fibrillation when pulmonary veins and appendage regions were paced but not when the free wall region was. Dantrolene (a ryanodine receptor blocker) did not reduce atrial fibrillation susceptibility. Conclusion: These data provide the first evidence of heterogenous calcium signaling across the healthy left atrium. Such basal regional differences may be exacerbated during the progression of atrial fibrillation and thus play a crucial role in focal arrhythmia initiation without ryanodine receptor gating modification.https://www.mdpi.com/2077-0383/12/3/746atrial fibrillationanimal modelpulmonary veincalciumoptical mapping |
| spellingShingle | Barbara C. Niort Alice Recalde Caroline Cros Fabien Brette Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria Journal of Clinical Medicine atrial fibrillation animal model pulmonary vein calcium optical mapping |
| title | Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria |
| title_full | Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria |
| title_fullStr | Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria |
| title_full_unstemmed | Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria |
| title_short | Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria |
| title_sort | critical link between calcium regional heterogeneity and atrial fibrillation susceptibility in sheep left atria |
| topic | atrial fibrillation animal model pulmonary vein calcium optical mapping |
| url | https://www.mdpi.com/2077-0383/12/3/746 |
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