Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

RATIONALE:Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Héctor O Rodríguez-Angulo, Jhoan Toro-Mendoza, Juan A Marques, Juan L Concepción, Rafael Bonfante-Cabarcas, Yoliver Higuerey, Luz E Thomas, Leandro Balzano-Nogueira, José R López, Alfredo Mijares
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2015
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Online Access:https://doi.org/10.1371/journal.pntd.0003512
https://doaj.org/article/98fc907fd8ca41bdb8e4c68d0e578c80
Description
Summary:RATIONALE:Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE:The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS:We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS:These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

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