Next Article in Journal
Intracellular Bacterial Symbionts in Corals: Challenges and Future Directions
Previous Article in Journal
Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
Previous Article in Special Issue
Chagas Disease-Related Mortality in Spain, 1997 to 2018
Article

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

1
Instituto Venezolano de Investigaciones Científicas, Caracas 1020A, Venezuela
2
Unidad de Biología Celular, Departamento de Ciencias Morfológicas, Programa de Medicina, Facultad de Ciencias de la vida, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela
3
Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain
4
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain
5
Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas 1060, Venezuela
6
Instituto de Investigación Sanitaria Hospital Universitario de la Princesa, 28009 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Dora Buonfrate
Microorganisms 2021, 9(11), 2208; https://doi.org/10.3390/microorganisms9112208
Received: 23 August 2021 / Revised: 13 October 2021 / Accepted: 19 October 2021 / Published: 23 October 2021
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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. View Full-Text
Keywords: Trypanosoma cruzi; chagas disease; sudden death; electrocardiograms; heart rate; arrhythmias; HCN4; ivabradine; isoproterenol; β2-adrenergic receptor Trypanosoma cruzi; chagas disease; sudden death; electrocardiograms; heart rate; arrhythmias; HCN4; ivabradine; isoproterenol; β2-adrenergic receptor
Show Figures

Figure 1

MDPI and ACS Style

Rodríguez-Angulo, H.O.; Colombet-Naranjo, D.; Maza, M.C.; Poveda, C.; Herreros-Cabello, A.; Mendoza, I.; Perera, J.C.; Goyo, J.D.; Gironès, N.; Fresno, M. Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis. Microorganisms 2021, 9, 2208. https://doi.org/10.3390/microorganisms9112208

AMA Style

Rodríguez-Angulo HO, Colombet-Naranjo D, Maza MC, Poveda C, Herreros-Cabello A, Mendoza I, Perera JC, Goyo JD, Gironès N, Fresno M. Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis. Microorganisms. 2021; 9(11):2208. https://doi.org/10.3390/microorganisms9112208

Chicago/Turabian Style

Rodríguez-Angulo, Héctor O., Diana Colombet-Naranjo, María C. Maza, Cristina Poveda, Alfonso Herreros-Cabello, Iván Mendoza, Juan C. Perera, Juan D. Goyo, Núria Gironès, and Manuel Fresno. 2021. "Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis" Microorganisms 9, no. 11: 2208. https://doi.org/10.3390/microorganisms9112208

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop