Abstract 4372: Granulocyte-Colony Stimulating Factor and Erythropoietin Synergistically Improve Left Ventricular Systolic Function in Heart Failure after Myocardial Infarction in Rats
Introduction: Granulocyte-colony stimulating factor (G-CSF) mobilizes multipotential progenitor cells from bone marrow into peripheral blood. While G-CSF can improve the left ventricular (LV) function after myocardial infarction (MI) in rodents, further augmentation of its beneficial effects is required to apply this therapy in the clinical setting in humans. Erythropoietin (EPO) increases angiogenesis, protects cardiomyocytes from apoptosis and reduces the infarct size. We hypothesized that EPO stabilizes progenitor cells mobilized by G-CSF and potentiates beneficial effects of G-CSF on the heart.
Objective: The purpose of this study was to examine the effect of G-CSF/EPO combination therapy on LV function in heart failure after MI in rats.
Methods: Rats were subjected to sham operation or MI. One week later, we performed LV functional studies by echocardiography in all surviving rats. The MI rats were then randomly assigned to 4 groups: I: saline (n=9), II: G-CSF (4.5 μg/kg/day) alone (n=9), III: EPO (3000 U/kg/day) alone (n=9), and IV: both G-CSF and EPO (n=9). Subcutaneous injections of these agents were repeated three days per week and continued for six weeks.
Results: Before treatment, MI rats exhibited a 40% decrease in LV fractional shortening (LVFS) and a 10% increase in the LV end-diastolic dimension (LVIDd) compared with sham-operated rats. In MI rats, the blood pressure, heart rate, LVFS, and LVIDd were similar among the four groups. After treatment, the erythrocyte count was significantly increased in groups III and IV compared with groups I and II. The body weight, heart rate, the LV posterior wall thickness and LVIDd did not differ among the four MI groups. The systolic blood pressure was slightly (10%) higher in groups III and IV than groups I and II. Compared with group I, LVFS increased by 11% in group II, by 12% in group III, and by 32% (p<0.05) in group IV. Perivascular fibrosis was significantly reduced in groups II and III compared with group I. This reduction was further augmented in group IV.
Conclusion: Combination therapy involving G-CSF and EPO synergistically improves the LV systolic function in heart failure after MI in rats and may be applicable to heart failure therapy in humans.