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

Article

关键词: HEART-DISEASE;    GENE-THERAPY;    ANGIOGENESIS;    ARTERIOGENESIS;    MECHANISMS;   

DOI  :  10.1161/hc4201.097835

来源: SCIE

【 摘 要 】

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 mug of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 mug/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (Pao, min 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 <0.05) and from 0.30 +/-0.16 to 0.23 +/-0.11 in the placebo group (P=NS). The treatment-induced difference in CFI was +0.11 +/-0.12 in the GM-CSF group and -0.07 +/-0.12 in the placebo group (P=0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment (P=0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo (P=NS). Conclusions-This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.

【 授权许可】

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