Modification of Post-Myocardial Infarction Granulocyte-Colony Stimulating Factor Therapy With Myelosuppressives

Abstract

Background The purpose of the present study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) in combination with myelosuppressives on post-myocardial infarction (MI) myocardial repair. Methods and Results Twenty-four hours after 30-min ischemia and reperfusion (day 0), rabbits were assigned to 4 treatment groups: myelosuppressives (M group), G-CSF (G group), the 2 in combination (MG group) or saline (S group). Significantly greater numbers of circulating stem cells were seen in the MG group than in the G group, with attenuated leukocytosis. In addition, MG caused the greatest upregulation of stromal cell-derived factor (SDF)-1 within the infarcted myocardium and thus recruitment of stem cells from the circulation into the infarcted tissue. This led to enhanced myocardial repair, as indicated by the numbers of bone marrow cell-derived cardiomyocytes and endothelial cells, reduction in scar tissue, improvement in cardiac function and reduction in left ventricular remodeling during the chronic phase of MI. These beneficial effects were entirely abolished by the administration of a CXCR4 antagonist AMD3100, which indicates the importance of CXCR4/SDF-1-axis as a mechanism underlying myocardial repair. Conclusion The combination of G-CSF and myelosuppressives may be a useful new therapy that overcomes the insufficiency seen with G-CSF alone. (Circ J 2007; 71: 580 - 590)