The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass.
OBJECTIVE
The number of circulating endothelial progenitor cells (EPC) depends on cytokine release and is also associated with cardiovascular risk factors. During cardiopulmonary bypass (CPB) the endothelium is the first organ to be affected by mechanical and immunologic stimuli. We hypothesized that the magnitude of EPC mobilization by CPB correlates with the pre-operative cardiovascular morbidity profile.


METHODS
EPC were quantified in blood samples from 30 patients who underwent cardiac surgery by magnetic bead isolation and fluorescence-activated cell sorting (FACS) analysis, based on concomitant expression of CD34, CD133 and CD309. Patients were divided into two groups based on the European System for Cardiac Operative Risk Evaluation (EuroSCORE): low risk (LR) and high risk (HR). Ten healthy volunteers served as controls. Samples were obtained before the start of CPB and at 1 and 24 h post-operatively. Plasma samples were collected for determination of release levels of cytokines and growth factors.


RESULTS
All CPB patients showed a significantly reduced basal number of EPC compared with healthy individuals (LR 5.60 +/- 0.39/mL, HR 3.89 +/- 0.34/ mL, versus control 0.807 +/- 0.82/mL, P = 0.012 versus LR, P< 0.001 versus HR). CPB induced EPC release that peaked 1 h after surgery (pre-operative 4.79 +/- 0.32/mL, 1 h 57.49 +/- 5.31/mL, 24 h 6.67 +/- 1.05/mL, P< 0.001 pre-operative versus 1 h, P< 0.001 pre-operative versus 24 h) and was associated with the duration of CPB. However, EPC release was significantly attenuated in HR patients (33.09 +/- 3.58/mL versus 81.89 +/- 4.36/mL at 1 h after CPB, P < 0.0001) and inversely correlated with the pre-operative EuroSCORE. Serum granulocyte-colony-stimulating factor (G-CSF), stem cell factor (SCF) and vascular endothelial growth factor (VEGF) levels increased throughout the observation period and were also correlated with the EPC count.


CONCLUSIONS
Cardiovascular risk factors influence the mobilization of EPC from the bone marrow after stimulation by CPB. This could be secondary to impaired mobilization or the result of increased EPC turnover, and may have implications for future cell therapy strategies in cardiac surgical patients.
Choi
Yeong-Hoon
YH
Heart Center of the University of Cologne, Department of Cardiothoracic Surgery, Cologne, Germany. yh.choi@uk-koeln.de
Neef
Klaus
K
Reher
Maike
M
Liakopoulos
Oliver J
OJ
Zeriouh
Mohamed
M
Wittwer
Thorsten
T
Stamm
Christof
C
Madershahian
Navid
N
Teschendorf
Peter
P
Wahlers
Thorsten
T
D000368:Aged; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000601:surgery*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011300:Preoperative Care; D020127:Recovery of Function / Q000502:physiology; D012307:Risk Factors; D019089:Stem Cell Factor / Q000097:blood; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000954:Antigens, Surface; D015415:Biomarkers; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor