Abstract
BackgroundChagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD.Methodology/Principal findingsMale C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180–200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni2+ or SEA0400.Conclusions/SignificanceThe present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.
Highlights
Chagas disease (CD) is a vector-borne disease caused by the parasite Trypanosoma cruzi that affects 6 to 7 million people worldwide, mostly in Latin America
In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz
In our study we evaluate the potential involvement of Na+/Ca2+ exchanger (NCX) in the arrhythmic phenotype of cardiomyocytes isolated from mice infected with Trypanosoma cruzi, between 180- and 200- days post-infection, which is considered the chronic phase of CD in this animal model
Summary
Chagas disease (CD) is a vector-borne disease caused by the parasite Trypanosoma cruzi that affects 6 to 7 million people worldwide, mostly in Latin America. The original route of transmission occurs through the triatomine vector, additional routes, including contaminated food and vertical transmission further contributes to increase the spread of the disease [1]. Around 30% of all infected individuals experience severe cardiac complications during the chronic phase of the disease leading to Chagasic CardioMyopathy (CCM). Clinical manifestations include non-sustained and sustained ventricular tachycardia and heart failure that, if not properly dealt with, will culminate in death [4]. Despite the severity of CCM, it is rather difficult to indicate proper therapeutic agents due to the incomplete knowledge of cellular biophysical mechanisms responsible for the generation of cardiac arrhythmias. Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD
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