title: Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.
abstract: Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with values in non-infected dogs. These findings strongly suggest that the temporary reduction in the parasite load that was induced by benznidazole treatment was not able to prevent myocardial lesions and diastolic dysfunction for long after treatment.
authors.affiliation: Laboratório de Doenças Parasitárias, Escola de Medicina, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil; Departamento de Farmácia e Nutrição, Universidade Federal do Espírito Santo, Alto Universitário, CEP 29500-000, Alegre, Espírito Santo, Brazil.
authors.forename: Fabiane M
authors.initials: FM
authors.lastname: Santos
authors.affiliation: Laboratório de Doenças Parasitárias, Escola de Medicina, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mazzeti
authors.affiliation: Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Caldas
authors.affiliation: Laboratório de Doenças Parasitárias, Escola de Medicina, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Karolina R
authors.initials: KR
authors.lastname: Gonçalves
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Wanderson G
authors.initials: WG
authors.lastname: Lima
authors.affiliation: Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena, 190, Santa Efigênia, CEP 30130-100, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rosália M
authors.initials: RM
authors.lastname: Torres
authors.affiliation: Laboratório de Doenças Parasitárias, Escola de Medicina, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil; Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil. Electronic address: mtbahia@nupeb.ufop.br.
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000469:parasitology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000469:parasitology*; D006801:Humans; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology*; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D059208:Parasite Load; D016133:Polymerase Chain Reaction; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole
keywords: Benznidazole; Diastolic dysfunction; Kinetoplast DNA follow-up; Trypanosoma cruzi