Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study.

BACKGROUND Experimentally, activated macrophages have been documented to induce vascular proliferation. METHODS AND RESULTS In 21 patients (age 74+/-9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 microg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 microg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (P(ao), mm Hg), distal coronary occlusive pressure (P(occl), mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P(occl)-CVP)/(P(ao)-CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21+/-0.14 to 0.31+/-0.23 in the GM-CSF group (P