ABSTRACT
BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.
Subject(s)
Animals , Female , Mice , Trypanosoma cruzi/physiology , Bone Marrow Cells/physiology , Chagas Cardiomyopathy/parasitology , Bone Marrow Transplantation/methods , Chagas Disease/parasitology , Cell Movement , Animal DiseasesABSTRACT
Objetivo: Avaliação do infarto do miocárdio (IM), induzido por isquemia e reperfusão em camundongos, por meio de análises ecocardiográficas, em equipamento específico para pequenos roedores. Medotologia: Camundongos machos e fêmeas C57BL/6 (oito semanas), pesando entre 20 e 25g, foram submetidos à indução do IM pelo protocolo isquemia e reperfusão (n=19), com um período de isquemia de 90 minutos e comparados a animais não infartados (n=10). Foram realizadas avaliações ecocardiográficas, antes do infarto e 8, 20 e 60 dias após a cirurgia com transdutor de alta resolução (30 MHz) específico para camundongos. Foram avaliados os diâmetros cavitários, fração de encurtamento pelo modo unidimensional e tempo de relaxamento isovolumétrico pelo Doppler, além de fração de ejeção calculada pelo método de Simpson, pelo modo bidimensional. Resultados: já na primeira análise, após o infarto do miocárdio, é possível evidenciar a dilatação do ventrículo esquerdo, em sístole (controle 2,10 +ou menos 0,43) mm versus infartado 2,83+ ou menos 0,46 mm, p<0,001) e diástole (controle 3,26+ ou menos 0,33 mm versus infartado 3,83 + ou menos 0,48 mm, p<0,01) e redução da fração de ejeção pelo método e Simpson (controle 74,63 + ou menos 8,29 versus infartado 62,58 + ou menos 11,62, p<0,05). Além disso, foi observado redução do tempo de relaxamento...