Circulation. 2001;104:2012-2017
doi: 10.1161/hc4201.097835
doi: 10.1161/hc4201.097835
(Circulation. 2001;104:2012.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Promotion of Collateral Growth by Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Coronary Artery Disease
A Randomized, Double-Blind, Placebo-Controlled Study
From the Swiss Cardiovascular Center Bern, Cardiology, University Hospital, Bern, Switzerland.
Correspondence to Christian Seiler, MD, FACC, FESC, Professor of Cardiology, University Hospital, CH-3010 Bern, Switzerland. E-mail christian.seiler.cardio{at}insel.ch
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 µg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 µg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (Pao, mm Hg), distal coronary occlusive pressure (Poccl, mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(Poccl-CVP)/(Pao-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.
Key Words: coronary disease • collateral circulation • growth substances • granulocyte-macrophage colony-stimulating factor
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