G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease.
OBJECTIVE
Granulocyte colony stimulating factor (G-CSF) therapy has been reported to be proarrhythmic. The in vivo mobilization of endothelial progenitor cells (EPCs) and the possible proarrhythmic effects in patients with severe coronary artery disease (CAD) and inducible ischemia have not been described.


METHODS
We treated 8 patients (mean age = 69 +/- 10) suffering from severe CAD and angina pectoris (CCS 3 +/- 0.5) despite optimal medical therapy with subcutaneous G-CSF over 7 days to mobilize EPCs (CD34(+), CD117(+)). ECG monitoring was performed throughout the treatment period. A 24-hour ECG was recorded before and after G-CSF application. Mobilization of EPCs was monitored by fluorescent activated cell sorter (FACS-Calibur, Becton-Dickinson, Franklin Lakes, NJ, USA) analysis. Other medications remained unchanged.


RESULTS
G-CSF therapy significantly increased peripheral leukocyte count from 7.45 +/- 2.4 to a peak of 42.2 +/- 10.9 x 10(3)/muL with a parallel rise in CD34(+) EPCs from 4.35 +/- 1.94 to 33.0 +/- 22.8/muL. The percentage of CD34(+)/CD117(+) cells changed from 0.32 +/- 0.25 to 0.24 +/- 0.28% (day of discharge, P = ns). During continuous ECG monitoring, no significant bradycardia, tachycardia, or changes in conduction were observed. Holter data collected after 7 days of G-CSF therapy showed no significant differences from baseline. A linear correlation (r = 0.76) was observed for the absolute values of deltaP wave duration and deltaCD34(+) concentration on day 2 compared to follow-up at 142 +/- 33 days, though it did not reach statistical significance (P = 0.29).


CONCLUSIONS
This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.
Wolfram
Oliver
O
Division of Cardiology, University Hospital Magdeburg, Magdeburg, Germany.
Jentsch-Ullrich
Kathleen
K
Wagner
Andrea
A
Hammwöhner
Matthias
M
Steinke
Rainer
R
Franke
Astrid
A
Zupan
Igor
I
Klein
Helmut U
HU
Goette
Andreas
A
D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000628:therapy; D018952:Antigens, CD34; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D003324:Coronary Artery Disease / Q000628:therapy*; D042783:Endothelial Cells; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007964:Leukocytosis; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor