Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing.
BACKGROUND
Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion.


METHODS
MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days.


RESULTS
At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar.


CONCLUSIONS
Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials.
Beohar
Nirat
N
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. n-beohar@northwestern.edu
Flaherty
James D
JD
Davidson
Charles J
CJ
Vidovich
Mladen
M
Singhal
Seema
S
Rapp
Jonathan A
JA
Erdogan
Ata
A
Lee
Daniel C
DC
Rammohan
Chidambaram
C
Brodsky
Adam
A
Wu
Edwin
E
Pieper
Karen
K
Virmani
Renu
R
Bonow
Robert O
RO
Mehta
Jayesh
J
D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D016014:Linear Models; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion / Q000379:methods*; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects*
D003287:Contrast Media; D016179:Granulocyte Colony-Stimulating Factor