A novel substrate for arrhythmias in Chagas disease.
Background 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. I...
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ftdoajarticles:oai:doaj.org/article:5fecf319b2974d3eb9837b2027cacc67 2023-05-15T15:13:43+02:00 A novel substrate for arrhythmias in Chagas disease. 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 2021-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009421 https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009421 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009421 https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67 PLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009421 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009421 2022-12-31T11:15:34Z Background 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. Methodology/principal findings 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. Conclusions/significance 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 6 e0009421 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background 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. Methodology/principal findings 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. Conclusions/significance 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 in Journal/Newspaper |
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://doi.org/10.1371/journal.pntd.0009421 https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009421 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009421 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009421 https://doaj.org/article/5fecf319b2974d3eb9837b2027cacc67 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009421 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
6 |
container_start_page |
e0009421 |
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1766344255483150336 |