Objective: Recent studies have suggested that granulocyte colony-stimulating factor (G-CSF) may improve cardiac function after acute myocardial infarction (AMI) by accelerating angiogenesis or cardiomyogenesis, but negative results and side effect of G-CSF have also been reported. However, no previous studies have used large animal models of ischemia/reperfusion to investigate the effect and side effect of G-CSF after AMI.
Methods: The diagonal branch of the left anterior descending coronary artery of swine was balloon-occluded for 1 h and then reperfused. The animals of the G-CSF group were injected with G-CSF subcutaneously (5.0 microg/kg/day) for 6 days after MI and then sacrificed after 4 weeks. The control group received the same volume of saline.
Results: There were no differences between the groups in the rate of thrombotic obstruction or progression of stenosis lesion in coronary angiography. The ejection fraction and end-diastolic volume in the G-CSF group were not significantly improved over the control values. The fibrotic area was significantly smaller in the G-CSF group than in the controls (P<0.05), and the numbers of vessels counted in anti-von Willebrand factor and anti-alpha-smooth muscle actin-stained sections were significantly larger (P<0.005 and P<0.05, respectively). The expression of collagen III mRNA was significantly lower in the G-CSF group than in the control in the infarct (P<0.0005) and border areas (P<0.005), and TGF-beta mRNA was significantly lower in the G-CSF group in the border area (P<0.05).
Conclusions: G-CSF could modify the healing process after AMI by accelerating angiogenesis in a swine ischemia/reperfusion model. At the dose administered, however, G-CSF did not seem to improve the global cardiac function.