Evolu??o da cardiopatia chag?sica em c?es tratados com Benznidazol na fase cr?nica da infec??o experimental pelo Trypanosoma cruzi.

A efic?cia do tratamento com Benznidazol (Bz) na fase cr?nica da infec??o e conseq?ente progn?stico da cardiopatia chag?sica permanece controversa. Neste estudo foram avaliados os efeitos do tratamento com Bz na evolu??o da cardiopatia chag?sica cr?nica, utilizando c?es infectados com a cepa Berenice-78 como modelo experimental. Os animais infectados foram divididos em dois grupos experimentais: (i) 12 c?es tratados na fase cr?nica com 7,0 mg de Bz/kg, divididos em duas doses di?rias, durante 60 dias; (ii) 12 c?es mantidos como controles n?o tratados. Outros 8 animais constitu?ram o grupo controle n?o-infectado. A parasitemia foi monitorada pela PCR realizada em amostras de sangue e tecido muscular card?aco coletados no 1o e 12o m?s ap?s o tratamento (MAT). A potente supress?o da parasitemia, induzida pelo tratamento com Bz, foi observada pelos resultados negativos em 81,9% (9 de 11) dos animais tratados em rela??o a 36,3% (4 de 11) nos animais n?o tratados quando realizada a PCR no sangue coletado no 1o MAT. Resultados semelhantes foram observados na PCR do tecido muscular card?aco, realizada no mesmo per?odo, quando o kDNA do parasito foi detectado somente em 33%,3 (2 de 6) dos animais tratados e em 100% dos animais n?o tratados. Um aumento dos resultados positivos na PCR do sangue e tecido foi detectado 12 MAT. Este resultado foi verificado em 60% (3 de 5) no sangue e 80% (4 de 5) no tecido muscular card?aco dos animais tratados. Para avalia??o da cardiomegalia e fun??o sist?lica ou diast?lica os animais foram examinados por ecocardiograma no 1o e 12o MAT. Foram mensurados os par?metros fra??o de encurtamento, volume do ?trio Esquerdo (AE), fra??o de eje??o, volume diast?lico e di?metro sist?lico do Ventr?culo Esquerdo (VE). Ap?s essa avalia??o, metade dos animais foi eutanaziada para realiza??o das an?lises histopatol?gicas no cora??o. O tratamento induziu uma redu??o de 20% a 36% de c?lulas inflamat?rias e deposi??o intrafascicular de col?geno no 1o MAT. Nesta fase da infec??o, n?o houve diferen?a significativa nos par?metros ecocardiogr?ficos mensurados entre os grupos de animais infectados (tratados ou n?o) e n?o infectados. Diferentemente, 12 MAT, as les?es card?acas foram semelhantes entre os animais infectados (tratados ou n?o) e significativamente maiores que naqueles n?o infectados. Vari?veis ecocardiogr?ficas relacionadas com cardiomegalia e disfun??o diast?lica tamb?m foram semelhantes entre os animais infectados (tratados ou n?o) e significativamente maiores que nos animais n?o infectados. De modo interessante, o tratamento preveniu altera??es na fun??o sist?lica, uma vez que n?o ocorreram diferen?as na fra??o de eje??o e fra??o de encurtamento entre os animais tratados e n?o infectados. Esses resultados demonstram que o tratamento com Bz na fase cr?nica da infec??o de c?es ? eficiente em prevenir as les?es card?acas imediatamente ap?s o tratamento e a fun??o sist?lica um longo tempo ap?s o t?rmino do tratamento.The analysis of available information reveals that the efficacy of benznidazole treatment in chronic chagasic infection is doubtful. In this study we evaluated the effect of Bz-treatment on the cardiac alterations using dogs infected with Berenice-78 strain as experimental model. The infected animals were divided in two experimental groups: (i) 12 dogs were Bz-treated at 7.0 mg/kg bid (Q12) for 60 days during the chronic phase; (ii) 12 dogs were maintained as non-treated control. Another 8 animals were maintained as non-infected control group. After the benznidazole-treatment the parasite load was monitored by blood and heart tissue PCR performed in the 1 st and 12 th months post-treatment (MPT). The potent suppression of parasitemia induced by Bz-treatment was associated with negative results of blood PCR performed in the 1 st MPT in 81.8% (9 of 11) of treated animals in relation to 36,3% (4 of 11) in those infected and non-treated animals. Similar results were observed in heart tissue PCR in the same period, when the parasite kDNA was detected only in 33,3% (2 of 6) of the treated animals. In contrast, 100% of infected and non-treated animals showed positive tissue PCR tests. An increase of positive results in blood and tissue PCR was detected 12 MPT. This result was verified in 60% (3 of 5) of blood and 80% (4 of 5) of tissue samples obtained of Bz-treated animals. For cardiomegaly and systolic or diastolic function evaluation the animals were examined by echocardiography in the 1 st and 12 th MPT. The parameters fractional shortening, Left Atrium (LA) volume, Left-ventricle (LV) ejection fraction, diastolic volume and systolic diameter were measured. After this evaluation a half of animals were euthanized in the same period for histopathological analysis of heart tissue. Bz-treatment led to a reduction of around 20% to 36% of inflammatory cells and intrafascicular collagen deposition when compared to non-treated animals in the first MPT. Additionally, all animals evaluated showed echocardiographic parameters similar to non-infected animals. M Differently, 12 MPT the intensity of cardiac lesions were similar to treated and non-treated animals and significantly larger than those detected in non-infected animals. Also, the echocardiographic parameters, related with cardiomegaly (LV and LA volume, LV systolic diameter) and diastolic function (LA volume), were similar among treated and non-treated animals and significantly higher than those observed in non-infected animals. Interestingly, the Bz-treatment was able to prevent alterations related to cardiac systolic functions (LV ejection and shortening fraction) such these parameters were similar to treated and non-infected animals. Taken together, the results indicate that Bz-treatment performance during the chronic phase of the dogs' infection is efficient in preventing cardiac lesions immediately after the treatment and systolic cardiac function long-time post-treatment