Cardioprotective effects of granulocyte colony-stimulating factor in swine with chronic myocardial ischemia.
OBJECTIVE
The aim of this study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on chronic myocardial ischemia in swine.


BACKGROUND
We recently have reported that G-CSF prevents cardiac remodeling and dysfunction after acute myocardial infarction in mice and swine. It remains unclear whether G-CSF has beneficial effects on chronic myocardial ischemia.


METHODS
An ameroid constrictor was placed on left circumflex coronary artery of swine. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were randomly assigned into the following two groups: 1) administration of vehicle (control group, n = 10), and 2) administration of G-CSF (10 microg/kg/day) for seven days (G-CSF group, n = 10).


RESULTS
Echocardiographic examination revealed that the G-CSF treatment prevented left ventricular dilation and dysfunction at eight weeks after the operation. Stress echocardiography revealed that G-CSF ameliorated the regional contractility of chronic myocardial ischemia. Morphological analysis revealed that the extent of myocardial fibrosis of the ischemic region was less in the G-CSF group than in control group. There were more vessels and less apoptotic cells at the ischemic region of the heart of the G-CSF group than control group. Moreover, Akt1 was more strongly activated in the heart of the G-CSF group than control group.


CONCLUSIONS
These findings suggest that G-CSF improves cardiac function of chronic myocardial ischemia through decreases in fibrosis and apoptotic death and an increase in vascular density in the ischemic region.
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Hiroshi
H
Hasegawa
Hiroyuki
H
Takano
Koji
K
Iwanaga
Masashi
M
Ohtsuka
Yingjie
Y
Qin
Yuriko
Y
Niitsuma
Kazutaka
K
Ueda
Tomohiko
T
Toyoda
Hiroyuki
H
Tadokoro
Issei
I
Komuro
D000818:Animals; D017209:Apoptosis; D002908:Chronic Disease; D004452:Echocardiography; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left
D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor