Granulocyte colony-stimulating factor improves early remodeling in isoproterenol-induced cardiac injury in rats.
BACKGROUND
Granulocyte colony-stimulating factor (G-CSF) has been used in some animal models and humans with well-established cardiovascular diseases. However, its effects in the initial stage of progressive non-ischemic heart failure are unknown.


METHODS
Wistar rats (260-300 g) were divided into three groups: control (without any intervention), ISO (150 mg/kg isoproterenol hydrochloride sc, once a day for two consecutive days), and ISO-GCSF (50 μg/kg/d G-CSF for 7 days beginning 24 h after the last administration of ISO). Echocardiography was performed at baseline and after 30 days of follow-up. Subsequently, animals were anesthetized for hemodynamic analysis. The left ventricle was removed for analysis of interstitial collagen deposition and cardiomyocyte hypertrophy.


RESULTS
Isoproterenol led to left ventricular dilation (control, 7.7 ± 0.14 mm; ISO, 8.7 ± 0.16 mm; ISO-GCSF 7.8 ± 0.09 mm; p < 0.05), myocardial fibrosis (control, 2.0 ± 0.18%; ISO, 9.1 ± 0.81%; ISO-GCSF 5.9 ± 0.58%; p < 0.05) and cardiomyocyte hypertrophy (control, 303 ± 10 μm(2); ISO, 356 ± 18 μm(2); ISO-GCSF 338 ± 11 μm(2); p < 0.05). However, G-CSF partially prevented collagen deposition and left ventricular enlargement, with a slight effect on hypertrophy. Characterizing a compensated stage of disease, hemodynamic analysis did not change.


CONCLUSIONS
G-CSF administered for 7 days was effective in preventing the onset of ventricular remodeling induced by high-dose isoproterenol with decreased collagen deposition and chamber preservation.
Department of Physiological Sciences, Federal University of Espirito Santo, Av. Marechal Campos 1468, Maruipe, 29042-755, Vitória, Espírito Santo, Brazil.
Ludimila
L
Forechi
Marcelo P
MP
Baldo
Diana
D
Meyerfreund
José G
JG
Mill
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D016179:Granulocyte Colony-Stimulating Factor; D003094:Collagen; D007545:Isoproterenol