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The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass
Authors:Yeong-Hoon Choi  Klaus Neef  Maike Reher  Oliver J. Liakopoulos  Mohamed Zeriouh  Thorsten Wittwer  Christof Stamm  Navid Madershahian  Peter Teschendorf  Thorsten Wahlers
Affiliation:1. Heart Center of the University of Cologne, Department of Cardiothoracic Surgery, Cologne, Germany;2. Center of Molecular Medicine Cologne, Cologne, Germany;3. German Heart Institute Berlin, Department of Cardiothoracic Surgery, Berlin, Germany;4. Department of Anesthesia, Cologne, Germany;1. Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China;2. Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China;1. Internal Medicine Department, State Medical University, Zaporozhye, Ukraine;2. Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine;1. Struttura Complessa Anestesia e Rianimazione, Ospedale Santa Croce e Carle, Cuneo, Italy;2. Coordinamento Regionale Prelievi d''Organo, San Giovanni Battista, Torino, Italy;1. Centro de Saúde Escola Barra Funda “Dr. Alexandre Vranjac”, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil;2. Medical School, Universidade de São Paulo, São Paulo, SP, Brazil;3. Department of Social Medicine, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil;1. Department of Surgery, Austin Hospital, Melbourne, Vic, Australia;2. Department of Cardiothoracic Surgery, The Wellington Regional Hospital, Wellington, New Zealand;3. Department of Administrative Informatics, Austin Hospital, Heidelberg, Melbourne, Vic, Australia;4. Department of Epidemiology and Preventive Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Vic, Australia;5. Department of Intensive Care, Austin Hospital, Melbourne, Vic, Australia;6. Department of Cardiac Surgery, Austin Hospital, Melbourne, Vic, Australia;1. Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;2. Department of Cardiovascular Disease Prevention, Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan;3. Research and Clinical Center for Yusho and Dioxin, Kyusyu University, Fukuoka, Japan;4. Department of Island and Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;5. Center for Comprehensive Community Care Education, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Abstract:Background aimsThe 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.MethodsEPC 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.ResultsAll 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.ConclusionsCardiovascular 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.
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