Key result
Perfusion of isolated rat hearts with >50 kDa proteins secreted by T. cruzi induced reversible bradycardia, complete atrioventricular block, and ventricular fibrillation, which were abolished by preincubation with chagasic patient serum.
Why the study?
Do immunogenic proteins secreted by T. cruzi induce arrhythmias in isolated rat hearts?
Do immunogenic proteins secreted by T. cruzi induce arrhythmias in isolated rat hearts?
Proteins secreted by T. cruzi (>50 kDa) directly induce reversible bradycardia and arrhythmias in isolated rat hearts, suggesting a pathophysiological role in Chagas cardiomyopathy.
May implicate T. cruzi secreted proteins in Chagas arrhythmias; hypothesis-generating and requires validation in human models.
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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Rodríguez‐Angulo et al. (2015) studied Chagas cardiomyopathy (n=17). T. cruzi conditioned infected medium (CMi) >50 kDa fraction vs. Conditioned medium control (CMc) and CMi preincubated with chagasic serum was evaluated on Heart rate kinetics and occurrence of arrhythmias (p=<0.05). Perfusion of isolated rat hearts with >50 kDa proteins secreted by T. cruzi induced reversible bradycardia, complete atrioventricular block, and ventricular fibrillation, which were abolished by preincubation with chagasic patient serum.
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