Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger...

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Autores principales:	Héctor O. Rodríguez-Angulo, Diana Colombet-Naranjo, María C. Maza, Cristina Poveda, Alfonso Herreros-Cabello, Iván Mendoza, Juan C. Perera, Juan D. Goyo, Núria Gironès, Manuel Fresno
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Trypanosoma cruzi</i> chagas disease sudden death electrocardiograms heart rate arrhythmias Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7490232ea3354253af36ae68c9e97df4
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spelling	oai:doaj.org-article:7490232ea3354253af36ae68c9e97df42021-11-25T18:24:16ZMolecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis10.3390/microorganisms91122082076-2607https://doaj.org/article/7490232ea3354253af36ae68c9e97df42021-10-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2208https://doaj.org/toc/2076-2607Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk.Héctor O. Rodríguez-AnguloDiana Colombet-NaranjoMaría C. MazaCristina PovedaAlfonso Herreros-CabelloIván MendozaJuan C. PereraJuan D. GoyoNúria GironèsManuel FresnoMDPI AGarticle<i>Trypanosoma cruzi</i>chagas diseasesudden deathelectrocardiogramsheart ratearrhythmiasBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2208, p 2208 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Trypanosoma cruzi</i> chagas disease sudden death electrocardiograms heart rate arrhythmias Biology (General) QH301-705.5
spellingShingle	<i>Trypanosoma cruzi</i> chagas disease sudden death electrocardiograms heart rate arrhythmias Biology (General) QH301-705.5 Héctor O. Rodríguez-Angulo Diana Colombet-Naranjo María C. Maza Cristina Poveda Alfonso Herreros-Cabello Iván Mendoza Juan C. Perera Juan D. Goyo Núria Gironès Manuel Fresno Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
description	Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk.
format	article
author	Héctor O. Rodríguez-Angulo Diana Colombet-Naranjo María C. Maza Cristina Poveda Alfonso Herreros-Cabello Iván Mendoza Juan C. Perera Juan D. Goyo Núria Gironès Manuel Fresno
author_facet	Héctor O. Rodríguez-Angulo Diana Colombet-Naranjo María C. Maza Cristina Poveda Alfonso Herreros-Cabello Iván Mendoza Juan C. Perera Juan D. Goyo Núria Gironès Manuel Fresno
author_sort	Héctor O. Rodríguez-Angulo
title	Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
title_short	Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
title_full	Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
title_fullStr	Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
title_full_unstemmed	Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
title_sort	molecular remodeling of cardiac sinus node associated with acute chagas disease myocarditis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7490232ea3354253af36ae68c9e97df4
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Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

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