{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:29:03Z","timestamp":1760236143392,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":": \u201cMinisterio de Econom\u00eda y competitividad\u201d and \u201cFondo Europeo de Desarrollo Regional\u201d (MINECO\/FEDER)","award":["SAF2015-63868-R"],"award-info":[{"award-number":["SAF2015-63868-R"]}]},{"name":"\u201cMinisterio de Econom\u00eda y competitividad\u201d and \u201cFondo Europeo de Desarrollo Regional\u201d  (MINECO\/FEDER)","award":["SAF2016-75988-R"],"award-info":[{"award-number":["SAF2016-75988-R"]}]},{"name":"&quot;Ministerio de Ciencia, Innovaci\u00f3n y Universidades-Agencia Estatal de Investigaci\u00f3n\u201d and \u201cFon-do Europeo de Desarrollo Regional\u201d (MICINN\/FEDER)","award":["PGC2018-096132-B-I00"],"award-info":[{"award-number":["PGC2018-096132-B-I00"]}]},{"name":".); \u201cUniversidad Aut\u00f3noma de Madrid-Banco de Santander\u201d Inter-university Cooperation Grant with Latin Am\u00e9rica","award":["SN\/2013"],"award-info":[{"award-number":["SN\/2013"]}]},{"name":"\u201cUniversidad Aut\u00f3noma de Madrid-Banco de Santander\u201d Inter-university Cooperation Grant with Latin Am\u00e9rica","award":["CEAL-AL\/2015-12"],"award-info":[{"award-number":["CEAL-AL\/2015-12"]}]},{"name":"\u201cRed de Investigaci\u00f3n de Centros de Enfermedades Tropicales\u201d (RICET)","award":["RICET RD12\/0018\/0004"],"award-info":[{"award-number":["RICET RD12\/0018\/0004"]}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["S-2010\/BMD-2332"],"award-info":[{"award-number":["S-2010\/BMD-2332"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u201cInstituto Venezolano de Investigaciones Cient\u00edficas\u201d","award":["IVIC-1365"],"award-info":[{"award-number":["IVIC-1365"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/microorganisms9112208","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:07:11Z","timestamp":1635113231000},"page":"2208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-103X","authenticated-orcid":false,"given":"H\u00e9ctor O.","family":"Rodr\u00edguez-Angulo","sequence":"first","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"},{"name":"Unidad de Biolog\u00eda Celular, Departamento de Ciencias Morfol\u00f3gicas, Programa de Medicina, Facultad de Ciencias de la vida, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Colombet-Naranjo","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda C.","family":"Maza","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0361-2232","authenticated-orcid":false,"given":"Cristina","family":"Poveda","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1137-891X","authenticated-orcid":false,"given":"Alfonso","family":"Herreros-Cabello","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-8424","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas 1060, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C.","family":"Perera","sequence":"additional","affiliation":[{"name":"Unidad de Biolog\u00eda Celular, Departamento de Ciencias Morfol\u00f3gicas, Programa de Medicina, Facultad de Ciencias de la vida, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan D.","family":"Goyo","sequence":"additional","affiliation":[{"name":"Unidad de Biolog\u00eda Celular, Departamento de Ciencias Morfol\u00f3gicas, Programa de Medicina, Facultad de Ciencias de la vida, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-2750","authenticated-orcid":false,"given":"N\u00faria","family":"Giron\u00e8s","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-5477","authenticated-orcid":false,"given":"Manuel","family":"Fresno","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2015). 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