Granulocyte colony stimulating factor in myocardial infarction with low ejection fraction.
BACKGROUND
We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia-reperfusion with left ventricle ejection fraction of <45% using a clinically relevant dosing and timing regimen.


METHODS
MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 microg/kg at time of reperfusion, followed by SC injections of 5 microg/kg days 5-9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.


RESULTS
GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38+/-2% vs. 33+/-2%, p<0.02) and improved wall motion score index (p<0.05). Histopathology revealed increased vascular density (p<0.05) and a trend toward increased areas of viable myocardium compared to control (p=0.058).


CONCLUSIONS
GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF (<45%). These results support future clinical trials with GCSF in selected patients with larger MI.
Angeli
Franca S
FS
Division of Cardiology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0103, USA.
Smith
Charles
C
Amabile
Nicolas
N
Shapiro
Mia
M
Bartlett
Lauren
L
Virmani
Renu
R
Chatterjee
Kanu
K
Boyle
Andrew
A
Grossman
William
W
Yeghiazarians
Yerem
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002404:Catheterization; D002465:Cell Movement / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D034421:Sus scrofa; D013997:Time Factors; D014463:Ultrasonography
D016179:Granulocyte Colony-Stimulating Factor