Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise
The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SC...
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eLife Sciences Publications Ltd
2023-02-01
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| Online Access: | https://elifesciences.org/articles/80710 |
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| author | Alexandra Polyák Leila Topal Noémi Zombori-Tóth Noémi Tóth János Prorok Zsófia Kohajda Szilvia Déri Vivien Demeter-Haludka Péter Hegyi Viktória Venglovecz Gergely Ágoston Zoltán Husti Péter Gazdag Jozefina Szlovák Tamás Árpádffy-Lovas Muhammad Naveed Annamária Sarusi Norbert Jost László Virág Norbert Nagy István Baczkó Attila S Farkas András Varró |
| author_facet | Alexandra Polyák Leila Topal Noémi Zombori-Tóth Noémi Tóth János Prorok Zsófia Kohajda Szilvia Déri Vivien Demeter-Haludka Péter Hegyi Viktória Venglovecz Gergely Ágoston Zoltán Husti Péter Gazdag Jozefina Szlovák Tamás Árpádffy-Lovas Muhammad Naveed Annamária Sarusi Norbert Jost László Virág Norbert Nagy István Baczkó Attila S Farkas András Varró |
| author_sort | Alexandra Polyák |
| collection | DOAJ |
| description | The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training. |
| first_indexed | 2024-04-10T00:37:00Z |
| format | Article |
| id | doaj.art-02b3774e90e748519b88740b22b943d6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T00:37:00Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-02b3774e90e748519b88740b22b943d62023-03-14T12:56:45ZengeLife Sciences Publications LtdeLife2050-084X2023-02-011210.7554/eLife.80710Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exerciseAlexandra Polyák0Leila Topal1Noémi Zombori-Tóth2Noémi Tóth3János Prorok4Zsófia Kohajda5Szilvia Déri6Vivien Demeter-Haludka7Péter Hegyi8https://orcid.org/0000-0003-0399-7259Viktória Venglovecz9Gergely Ágoston10Zoltán Husti11Péter Gazdag12Jozefina Szlovák13Tamás Árpádffy-Lovas14Muhammad Naveed15Annamária Sarusi16Norbert Jost17László Virág18https://orcid.org/0000-0002-0592-2608Norbert Nagy19https://orcid.org/0000-0002-4557-8442István Baczkó20https://orcid.org/0000-0002-9588-0797Attila S Farkas21András Varró22https://orcid.org/0000-0003-0745-3603Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; ELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network, Szeged, HungaryELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryCentre for Translational Medicine and Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryInstitute of Family Medicine, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; ELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; ELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, HungaryDepartment of Internal Medicine, Cardiology ward, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; ELKH-SZTE Research Group for Cardiovascular Pharmacology, Eötvös Loránd Research Network, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, HungaryThe health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.https://elifesciences.org/articles/80710endurance trainingdogelectrophysiologyarrhythmia |
| spellingShingle | Alexandra Polyák Leila Topal Noémi Zombori-Tóth Noémi Tóth János Prorok Zsófia Kohajda Szilvia Déri Vivien Demeter-Haludka Péter Hegyi Viktória Venglovecz Gergely Ágoston Zoltán Husti Péter Gazdag Jozefina Szlovák Tamás Árpádffy-Lovas Muhammad Naveed Annamária Sarusi Norbert Jost László Virág Norbert Nagy István Baczkó Attila S Farkas András Varró Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise eLife endurance training dog electrophysiology arrhythmia |
| title | Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| title_full | Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| title_fullStr | Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| title_full_unstemmed | Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| title_short | Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| title_sort | cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise |
| topic | endurance training dog electrophysiology arrhythmia |
| url | https://elifesciences.org/articles/80710 |
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