Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function.
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 10(3) 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 (VO(2)), carbon dioxide production (VCO(2)), 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
Simone G
SG
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
Vasconcelos
Juliana F
JF
Costa
Claudio R S
CR
Klein
Wilfried
W
Lima
Ricardo S
RS
Guimarães
Patrícia
P
Vidal
Daniel T A
DT
Mendez
Lucas C
LC
Ribeiro-Dos-Santos
Ricardo
R
Soares
Milena B P
MB
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014355:Chagas Disease / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011994:Recombinant Proteins
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011994:Recombinant Proteins; D002245:Carbon Dioxide; D016179:Granulocyte Colony-Stimulating Factor