A novel substrate for arrhythmias in Chagas disease

Autor(es)

Santos-Miranda, Artur ^[1] ; Joviano-Santos, Julliane V. ^[1] ; Sarmento, Jaqueline O. ^[1] ; Costa, Alexandre D. ^[2] ; Soares, Allysson T. C. ^[3] ; Machado, Fabiana S. ^[3] ; Cruz, Jader S. ^{[3, 2]} ; Roman-Campos, Danilo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[2] Univ Fed Minas Gerais, Dept Physiol & Pharmacol, Inst Biol Sci, Belo Horizonte, MG - Brazil

^[3] Univ Fed Minas Gerais, Dept Biochem & Immunol, Inst Biol Sci, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 15, n. 6 JUN 2021.
• Citações Web of Science: 0

Resumo

Background 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. 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 findings Male 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/Significance The 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. Author summary Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. There are several substrates for arrhythmias in the heart. Some of them involve changes in the electrical properties of cardiomyocytes, the working cells of the heart. 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. In our study we found several arrhythmogenic membrane potential oscillations during action potential measurements, in rest and using a protocol to simulate a pause after a tachycardia. Using pharmacological approach, we determine that NCX significantly contributed to the arrhythmogenic phenomena observed. Thus, in our study we demonstrate that NCX may be relevant to the cellular arrhythmogenic profile observed in cardiomyocytes during the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition. (AU)

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