A novel substrate for arrhythmias in Chagas disease.

<h4>Background</h4>Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open question...

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Autores principales:	Artur Santos-Miranda, Julliane V Joviano-Santos, Jaqueline O Sarmento, Alexandre D Costa, Allysson T C Soares, Fabiana S Machado, Jader S Cruz, Danilo Roman-Campos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67
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spelling	oai:doaj.org-article:5fecf319b2974d3eb9837b2027cacc672021-11-25T06:31:49ZA novel substrate for arrhythmias in Chagas disease.1935-27271935-273510.1371/journal.pntd.0009421https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc672021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009421https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD.<h4>Methodology/principal findings</h4>Male C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180-200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni2+ or SEA0400.<h4>Conclusions/significance</h4>The present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.Artur Santos-MirandaJulliane V Joviano-SantosJaqueline O SarmentoAlexandre D CostaAllysson T C SoaresFabiana S MachadoJader S CruzDanilo Roman-CamposPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009421 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Artur Santos-Miranda Julliane V Joviano-Santos Jaqueline O Sarmento Alexandre D Costa Allysson T C Soares Fabiana S Machado Jader S Cruz Danilo Roman-Campos A novel substrate for arrhythmias in Chagas disease.
description	<h4>Background</h4>Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD.<h4>Methodology/principal findings</h4>Male C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180-200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni2+ or SEA0400.<h4>Conclusions/significance</h4>The present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.
format	article
author	Artur Santos-Miranda Julliane V Joviano-Santos Jaqueline O Sarmento Alexandre D Costa Allysson T C Soares Fabiana S Machado Jader S Cruz Danilo Roman-Campos
author_facet	Artur Santos-Miranda Julliane V Joviano-Santos Jaqueline O Sarmento Alexandre D Costa Allysson T C Soares Fabiana S Machado Jader S Cruz Danilo Roman-Campos
author_sort	Artur Santos-Miranda
title	A novel substrate for arrhythmias in Chagas disease.
title_short	A novel substrate for arrhythmias in Chagas disease.
title_full	A novel substrate for arrhythmias in Chagas disease.
title_fullStr	A novel substrate for arrhythmias in Chagas disease.
title_full_unstemmed	A novel substrate for arrhythmias in Chagas disease.
title_sort	novel substrate for arrhythmias in chagas disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67
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A novel substrate for arrhythmias in Chagas disease.

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