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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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Autores principales: Polyák, Alexandra, Topal, Leila, Zombori-Tóth, Noémi, Tóth, Noémi, Prorok, János, Kohajda, Zsófia, Déri, Szilvia, Demeter-Haludka, Vivien, Hegyi, Péter, Venglovecz, Viktória, Ágoston, Gergely, Husti, Zoltán, Gazdag, Péter, Szlovák, Jozefina, Árpádffy-Lovas, Tamás, Naveed, Muhammad, Sarusi, Annamária, Jost, Norbert, Virág, László, Nagy, Norbert, Baczkó, István, Farkas, Attila S, Varró, András
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014074/
https://www.ncbi.nlm.nih.gov/pubmed/36815557
http://dx.doi.org/10.7554/eLife.80710
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author Polyák, Alexandra
Topal, Leila
Zombori-Tóth, Noémi
Tóth, Noémi
Prorok, János
Kohajda, Zsófia
Déri, Szilvia
Demeter-Haludka, Vivien
Hegyi, Péter
Venglovecz, Viktória
Ágoston, Gergely
Husti, Zoltán
Gazdag, Péter
Szlovák, Jozefina
Árpádffy-Lovas, Tamás
Naveed, Muhammad
Sarusi, Annamária
Jost, Norbert
Virág, László
Nagy, Norbert
Baczkó, István
Farkas, Attila S
Varró, András
author_facet Polyák, Alexandra
Topal, Leila
Zombori-Tóth, Noémi
Tóth, Noémi
Prorok, János
Kohajda, Zsófia
Déri, Szilvia
Demeter-Haludka, Vivien
Hegyi, Péter
Venglovecz, Viktória
Ágoston, Gergely
Husti, Zoltán
Gazdag, Péter
Szlovák, Jozefina
Árpádffy-Lovas, Tamás
Naveed, Muhammad
Sarusi, Annamária
Jost, Norbert
Virág, László
Nagy, Norbert
Baczkó, István
Farkas, Attila S
Varró, András
author_sort Polyák, Alexandra
collection PubMed
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.
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spelling pubmed-100140742023-03-15 Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise Polyák, Alexandra Topal, Leila Zombori-Tóth, Noémi Tóth, Noémi Prorok, János Kohajda, Zsófia Déri, Szilvia Demeter-Haludka, Vivien Hegyi, Péter Venglovecz, Viktória Ágoston, Gergely Husti, Zoltán Gazdag, Péter Szlovák, Jozefina Árpádffy-Lovas, Tamás Naveed, Muhammad Sarusi, Annamária Jost, Norbert Virág, László Nagy, Norbert Baczkó, István Farkas, Attila S Varró, András eLife Medicine 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. eLife Sciences Publications, Ltd 2023-02-23 /pmc/articles/PMC10014074/ /pubmed/36815557 http://dx.doi.org/10.7554/eLife.80710 Text en © 2023, Polyák, Topal et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Polyák, Alexandra
Topal, Leila
Zombori-Tóth, Noémi
Tóth, Noémi
Prorok, János
Kohajda, Zsófia
Déri, Szilvia
Demeter-Haludka, Vivien
Hegyi, Péter
Venglovecz, Viktória
Ágoston, Gergely
Husti, Zoltán
Gazdag, Péter
Szlovák, Jozefina
Árpádffy-Lovas, Tamás
Naveed, Muhammad
Sarusi, Annamária
Jost, Norbert
Virág, László
Nagy, Norbert
Baczkó, István
Farkas, Attila S
Varró, András
Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise
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 Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014074/
https://www.ncbi.nlm.nih.gov/pubmed/36815557
http://dx.doi.org/10.7554/eLife.80710
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