Emerging hematological targets and therapy for cardiovascular disease: From bench to bedside
Recent experimental studies have shown that granulocyte-colony-stimulating factor (G-CSF) enhanced cardiac function after infarction. The concept of direct cytokine or cell-mediated effects on postischemic myocardial function was tested in the setting of human myocardial infarction subjected to percutaneous coronary intervention. In the FIRSTLINE-AMI study 50 consecutive patients with first ST-elevation myocardial infarction were randomly assigned to receive either 10 microg/kg G-CSF for 6 days after percutaneous coronary intervention in addition to standard medication, or standard care alone. G-CSF administration led to mobilization of CD34(+) mononuclear stem cells (MNC(CD34+)), with a 20-fold increase to 64 +/- 37 MNC(CD34+)/microl at day 6 without significant associated changes in rheology, blood viscosity or inflammatory reaction, or any major adverse effects. At 4 months the G-CSF group showed improved left ventricular ejection fraction of 54 +/- 8% versus 48 +/- 4% at baseline (P <0.001), and no evidence of left ventricular end-diastolic remodeling, with a diameter of 55 +/- 5 mm and improved segmental wall thickening (P <0.001); conversely, in control patients left ventricular ejection fraction was 43 +/- 5% at 4 months (P <0.001), with increased left ventricular end-diastolic dimension of 58 +/- 4 mm (P <0.001), and no segmental wall thickening. In conclusion, the FIRSTLINE-AMI study showed that G-CSF administration and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of human myocardium and prevention of remodeling without evidence of aggravated atherosclerosis.