The Syrian hamster as a model for the dilated cardiomyopathy of Chagas’ disease: a quantitative echocardiographical and histopathological analysis

Chagas disease cardiomyopathy: current concepts of an old disease

“…HIGUCHI and co-workers showed that the frequency of myocarditis was higher among patients with severe CCC than in patients with less severe forms of the disease (HIGUCHI et al, 1987). Accordingly, our group showed a significant correlation between myocarditis and fibrosis and ventricular dilation in the Syrian hamster model of CCC (BILATE et al, 2003). However, in spite of the substantial evidence supporting a role for immune responses in myocardial damage, the nature of the antigen eliciting the destructive immune response remains elusive.…”

“…Furthermore, T. cruzi-specific CD8+ T cells have been isolated from endomyocardial biopsies of a CCC patient (FONSECA et al, 2005), providing evidence for the recruitment and expansion of T. cruzi-specific T cells in the myocardium, possibly related to the presence of the parasite antigen. In experimental T. cruzi infection, a higher inoculum (BILATE et al, 2003) or higher parasite load in the acute phase (MARINHO et al, 1999) are associated with more aggressive heart disease, suggesting a relationship between parasite burden and severity of disease in animal models. However, T. cruzi DNA -but not intact T. cruzi -was detected in the hearts of both IND and CCC patients (reviewed in CUNHA-NETO et al, 2006), which does not support an association between parasite presence and CCC in humans.…”

“…Given that TNF-α levels are increased among CCC patients as compared to IND individuals (FERREIRA et al, 2003;TALVANI et al, 2004), and that T cells infiltrating the heart of CCC patients predominantly produce IFN-γ and TNF-α (ABEL et al, 2001), one may hypothesize that inflammatory cytokine inhibition could ameliorate CCC progression. In order to test this, we used the hamster model for CCC (RAMIREZ et al, 1994;BILATE et al, 2003) to evaluate whether TNF-α blockade could attenuate disease progression. To our surprise, blocking TNF-α with a soluble TNF-α receptor (Etanercept) during the chronic phase of T. cruzi infection worsened CCC, as shown by impaired cardiac function, a hallmark of human CCC (BILATE et al, 2007).…”

Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy

“…On the other hand, the blockade of CCR5 with Met-RANTES significantly decreased the intensity of cardiac inflammatory infiltrate, suggesting that lymphocyte migration to the myocardium during acute infection is dependent on CCR5 ligands (Marino et al 2004). The Syrian hamster model of T. cruzi infection reproduces the range of different outcomes of human Chagas disease (Ramirez et al 1994, Bilate et al 2003. During acute T. cruzi infection, hamsters displaying high cardiac parasitism also showed increased expression of TNF-α, IFN-γ, IL-10 and CCL3 mRNA, as well as acute phase signs such as weight loss, vomiting and diarrhoea while animals with low cardiac parasitism displayed a modest increase in cytokine/chemokine mRNA and no acute phase signs .…”

Current and Future Chemotherapy for Chagas Disease

“…Current chronically infected mouse models develop an anti-inflammatory infiltrate and fibrosis in the heart, hallmarks of the disease in humans, but development of a model closely resembling human chronic Chagas cardiomyopathy with extensive fibrosis, segmental myocardial abnormalities and macroscopic ventricle dilatation after a period of absence of signs is still to report 59 .…”