Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Abstract

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

“…We have previously [ 15 ] demonstrated that cardiac damage can be estimated based on the amount of AST released into the coronary effluent. In the present study, we carried out serial AST enzymatic measurements as an internal control.…”

“…cruzi GP82, [ 13 ] GP90 and GP35/50 proteins [ 31 ] have been described as involved in both the modulation of calcium increase in the host cell and in determining the invasiveness of the parasite strain. Our group [ 15 ], demonstrated that T . cruzi -conditioned medium was able to increase the frequency of occurrence of tachyarrhythmia and cause a decrease in the heart rate during post-ischemic recovery.…”

“…In this study, we used a Bolztmann equation for fitting to HR kinetics during recirculation-reoxygenation protocol as previously described [ 15 ] to model the I/R process.…”

“…However, there are few reports that have linked protein secretion by T . cruzi with arrhythmias [ 15 ]. Consequently, the aim this study is to demonstrate that proteins present in T .…”

Host cell cAMP-Epac pathway inhibition by hawthorn extract as a potential treatment for Chagas disease

“…This cardiac manifestation is considered an arrhythmogenic cardiomyopathy and is characterized by atrial and ventricular arrhythmias and a wide variety of conductive system abnormalities [10]. On the other hand, the presence of fibrosis and hypertrophy was observed in a 3D culture model of T. cruzi infected cardiomyocytes [32,33] and, also, an increase in the frequency of tachyarrhythmias was recorded using infected VERO medium [34], suggesting that T. cruzi secreted proteins have the ability to potentiate arrhythmias, presumably by increasing Ca 2+ intracellular levels. In turn, Epac-mediated activation is necessary for the stimulation of Ca 2+ induced by Ca 2+ release through ryanodine receptors (RyR) in cardiomyocytes [35], while Epac1 depletion protects against myocardial ischemia-reperfusion (I-R) damage, reducing infarct size and cell apoptosis [36].…”