Plasma levels and functional properties of human endothelial progenitor cells following exposure to sevoflurane

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB085

Poster Communications: Plasma levels and functional properties of human endothelial progenitor cells following exposure to sevoflurane

B. Pavel1, M. Gilca1, L. Ceafalan1, C. Stancu2, L. Niculescu2, E. Andrei2, M. Popescu1,3, I. Stanca3, M. Melnic3, A. Popescu1,3, D. Corneci1,3, D. Dimulescu1,3, A. Vlad1,3

1. University of Medicine and Pharmacy "Carol Davila", Romania, Bucharest, Romania. 2. "Nicolae Simionescu" CBPI, Bucharest, Romania. 3. "Elias" Emergency University Hospital, Bucharest, Romania.

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The risk of in-stent restenosis is increased in patients with low levels of endothelial progenitor cells (EPCs), while volatile anesthetics are able to improve stem cells biology. Thus, we hypothesized that sevoflurane could stimulate EPCs mobilization in patients undergoing percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment, as well as their viability and adhesion, events that would suggest a protective effect of anesthetic preconditioning (APC) against in-stent restenosis. EPCs number was assessed by flow-cytometry and culture assay before exposure to sevoflurane (baseline) and 24 hrs after the preconditioning procedure, corresponding to the late window of APC protection, in blood samples obtained from patients with coronary artery disease (CAD). The subjects were exposed before PCI to sevoflurane (1 MAC in 50% O2, administered in 2 cycles of 15 minutes interrupted by 10 minutes wash-out; study group, n=5) or to oxygen (sham group, n=5). Cultures of EPCs derived from human cord blood mononuclear cells were preconditioned in vitro in day 6 with sevoflurane 2% in air/5% CO2, or incubated only with air/5% CO2 (sham control) for 2 hours in a modular chamber. EPCs viability and adhesion on monolayers of human umbilical vein endothelial cells (HUVEC) were evaluated 24 hours later. Values are means ± SEM, compared by ANOVA. Plasma CD45dim/CD34+/KDR+ and CD45dim/CD34+/KDR+/CD133+ mononuclear cell populations were not increased in sevoflurane treated versus sham group at 24 hours post-exposure. Although not statistically significant, the number of adherent DilAcLDL+/FITC-UEAI+ cells in 7 days old EPCs cultures from preconditioned patients were higher when compared to those of sham control subjects (185,67±23,95 vs 96,37±12,80, the values are expressed as % at 24 hours vs baseline; p<0.05). In the in vitro preconditioned EPCs cultures, sevoflurane discretely lowered the lactate dehydrogenase leakage (94.67%±1.54 vs control, n = 14, p < 0.05), increased the tetrazolium salt concentration (115.5%±4.15 vs control, n=15, p<0.001) and raised the number of adhered Dil-stained EPCs cells to HUVEC monolayers when compared to control (58.28±13.39 vs 27.67±5.15, n=4, p<0.05). Thus, in vitro exposure of human EPCs to sevoflurane increased their proliferation and adherence to HUVEC monolayers, whereas CAD patients with BMS deployment preconditioned with the same halogenate showed higher values for plasma EPCs enumerated in culture compared to the control group. Although preliminary, these results suggest a good potential of APC for increasing the number and activity of EPCs in stented CAD patients. A follow-up at 6 and 9 months is scheduled for assessing the risk of restenosis, if further experiments will provide relevant data.



Where applicable, experiments conform with Society ethical requirements.

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