Chagas cardiomyopathy : the potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogschronically infected with Trypanosoma cruzi.

Abstract

Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and therelevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the presentstudy, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzistrain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiacmuscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. Theeffect of the treatment on reducing the parasite load was monitored by blood PCR and blood cultureassays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function wasevaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatmentin reducing the parasite burden was demonstrated by a marked decrease in positive blood culture andPCR assay results until 30 days post-treatment. At this time, the PCR and blood culture assays yieldednegative 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 bloodculture assays at follow-up. The parasite load reduction induced by treatment was compatible with thelower degree of tissue damage among animals euthanized in the first month after treatment and withthe increased cardiac damage after this period, reaching levels similar to those in untreated animals atthe one-year follow-up. The two infected groups also presented similar, significantly smaller values forearly tissue septal velocity (E’ SIV) than the non-infected dogs did at this later time. Moreover, in thetreated animals, an increase in the E/E’ septal tissue filling pressure ratio was observed when comparedwith basal values as well as with values in non-infected dogs. These findings strongly suggest that thetemporary reduction in the parasite load that was induced by benznidazole treatment was not able toprevent myocardial lesions and diastolic dysfunction for long after treatment.