Midazolam Promotes the Mobilization of Endothelial Progenitor Cells and Increases the Plasma Concentration of VEGF in Rats with Myocardial Ischemia Treated with G-CSF

Abstract

Background: Midazolam is commonly used during the perioperative period in patients with cardiac operations, especially in the patients with myocardial ischemia (MI). Some studies have demonstrated that midazolam stimulates vascular endothelial growth factor (VEGF) release in aortic smooth muscle cells. As we all know, VEGF is a hypoxia-inducible factor, which enhances vascular permeability, promotes angiogenesis, and appears to play an important role in the mobilization of endothelial progenitor cells (EPCs). The aim of this study was to evaluate the effects of midazolam on both VEGF release and the mobilization of EPCs in rats with myocardial ischemia treated with granulocyte colony-stimulating factor (G-CSF).Methods: Thirty-six rats with myocardial ischemia were randomly divided into three groups (n=12): control group, G-CSF alone-group and G-CSF plus midazolam group (control group, G-CSF group and midazolam group), pretreated with G-CSF for five days, and followed by continuous infusion of saline and midazolam into the veins for six hours on the sixth day. The number of CD34+ mononuclear cells (MNCs) and EPCs, and the plasma concentrations of VEGF and C-reactive protein (CRP) were measured at the end of the six-hour infusion. Left ventricular end-diastolic pressure (LVEDP), and maximal and minimal rates of rise of pressure in the left ventricle (dp/dtmax and dp/dtmin, respectively) were measured with a modified non-circulating Langendorff apparatus.Results: Compared to the control group, rats in the G-CSF group had a higher concentration of VEGF and increased levels of CD34+ MNCs and EPCs (P<0.05). Whereas compared to the G-CSF group, the concentrations of VEGF and the number of CD34+ MNCs and EPCs in the midazolam group were significantly higher (P<0.05). The LVEDP of the rats in both the midazolam and G-SF groups were significantly lower than that of the control group (P<0.05); while the dp/dtmin of the rats in both the midazolam and G-CSF groups were significantly higher than that of the control group, and the dp/dtmin in the midazolam group was higher than that of the G-CSF group (P<0.05).Conclusions: G-CSF can increase VEGF concentration and promote EPC mobilization in rats with myocardial ischemia. Midazolam reinforces the above effects and increases vascular dilation. Citation: Ting-Ting Chen, Wei-Dong Mi, Gang Wang, Li-Bing Li. Midazolam promotes the mobilization of endothelial progenitor cells and increases the plasma concentration of VEGF in rats with myocardial ischemia treated with G-CSF. J Anesth Perioper Med 2016; 3: 119-124. doi: 10.24015/JAPM.2016.0016This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.