Cytokine combination therapy with erythropoietin and granulocyte colony stimulating factor in a porcine model of acute myocardial infarction.
OBJECTIVE
Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.


METHODS
MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.


RESULTS
At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.


CONCLUSIONS
Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF.
Angeli
Franca S
FS
Division of Cardiology, Department of Medicine, University of California, 505 Parnassus Avenue, L-523, Box 0103, San Francisco, CA 94143-0103, USA.
Amabile
Nicolas
N
Shapiro
Mia
M
Mirsky
Rachel
R
Bartlett
Lauren
L
Zhang
Yan
Y
Virmani
Renu
R
Chatterjee
Kanu
K
Boyle
Andrew
A
Grossman
William
W
Yeghiazarians
Yerem
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D004452:Echocardiography / Q000379:methods; D004921:Erythropoietin / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine
D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor
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