The effect of granulocyte colony stimulating factor on regional and global myocardial function in the porcine infarct model.
BACKGROUND
Stem cell therapy has been shown to attenuate the reduction of left ventricular function following myocardial infarction. Most studies have utilized either a direct injection or intra-coronary infusion of cells, but cytokine mobilization of stem cells in the murine model of acute myocardial infarction has been reported to induce similar improvement in cardiac function.


METHODS
An antero-apical infarction was induced in swine by balloon occlusion, followed by the daily administration of granulocyte colony stimulating factor (G-CSF) or placebo for 5 days. We used left ventricular angiograms and 2D echocardiograms to assess global function, and 3D echocardiograms to assess regional function prior to infarction, immediately following infarction, and at 8 weeks. Histologic evaluation was performed after sacrifice at 8 weeks.


RESULTS
There was no significant difference in early or late post-infarction left ventricular ejection fraction or in myocardial histology between the two groups. Following G-CSF therapy, however, 3D echocardiography demonstrated that the regional ejection fractions of the infarcted segments showed a 50.3% improvement in the G-CSF pigs compared to a 7.4% deterioration in the untreated pigs (p=0.005).


CONCLUSIONS
Global left ventricular ejection fraction remained unchanged, and there is no histologic evidence for infarct attenuation following G-CSF infusion in the porcine infarct-reperfusion model. There was recovery of regional function in the infarcted segment in the G-CSF pigs. These data suggest that bone marrow mobilization in larger species has limited potential as a therapy designed to replace infarcted myocardium or to improve overall cardiac function, although further studies are needed to examine regional effect in the infarct area.
Lee
Steve S
SS
Division of Cardiology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, United States.
Naqvi
Tasneem Z
TZ
Forrester
James
J
Cattley
Russ
R
Shah
Atman
A
Frantzen
Malka
M
Miyamoto
Takashi
T
Kaufman
Stephen
S
Price
Matthew J
MJ
Lill
Michael
M
Makkar
Raj R
RR
D000818:Animals; D003094:Collagen / Q000378:metabolism; D017023:Coronary Angiography; D019560:Echocardiography, Three-Dimensional; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles; D007958:Leukocyte Count; D009203:Myocardial Infarction / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine
D016179:Granulocyte Colony-Stimulating Factor; D003094:Collagen