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Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function

Simone G. Macambira^*,, Juliana F. Vasconcelos^*, Claudio R. S. Costa^*, Wilfried Klein, Ricardo S. Lima^*, Patrícia Guimarães^*, Daniel T. A. Vidal^*, Lucas C. Mendez^*, Ricardo Ribeiro-dos-Santos^*, and Milena B. P. Soares^*,,1

^* Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil;

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;

Instituto de Biologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; and

Hospital São Rafael, Salvador, Bahia, Brazil

¹ Correspondence: Milena Botelho Pereira Soares, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz. 121, Rua Waldemar Falcão, Candeal, Salvador, Bahia, Brazil, 40.296-710. E-mail: milena{at}bahia.fiocruz.br

This study investigates the effects of granulocyte colony-stimulating factor (G-CSF) therapy in experimental chronic chagasic cardiomyopathy. Chagas disease is one of the leading causes of heart failure in Latin America and remains without an effective treatment other than cardiac transplantation. C57BL/6 mice were infected with 10³ trypomastigotes of Trypanosoma cruzi, and chronic chagasic mice were treated with G-CSF or saline (control). Evaluations following treatment were functional, immunological, and histopathological. Comparing hearts of G-CSF-treated mice showed reduced inflammation and fibrosis compared to saline-treated chagasic mice. G-CSF treatment did not alter the parasite load but caused an increase in the number of apoptotic inflammatory cells in the heart. Cardiac conductance disturbances in all infected animals improved or remained stable due to the G-CSF treatment, whereas all of the saline-treated mice deteriorated. The distance run on a treadmill and the exercise time were significantly greater in G-CSF-treated mice when compared to chagasic controls, as well as oxygen consumption (O₂), carbon dioxide production (CO₂), and respiratory exchange ration (RER) during exercise. Administration of G-CSF in experimental cardiac ischemia had beneficial effects on cardiac structure, which were well correlated with improvements in cardiac function and whole animal performance.—Macambira, S. G., Vasconcelos, J. F., Costa, C. R. S., Klein, W., Lima, R. S., Guimarães, P., Vidal, D. T. A., Mendez, L. C., Ribeiro-dos-Santos, R., Soares, M. B. P. Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function.

Key Words: chagasic cardiomyopathy • inflammation • arrhythmias • treadmill performance