Exposure to volatile anesthetics triggers an adaptive response similar to that achieved by ischemic preconditioning, in both temporal and mechanistic patterns. Current experimental data suggests a possible link between cardioprotection provided by anesthetic preconditioning and myocardial tissue regeneration through endothelial progenitor cells.Objectives
This study aims at demonstrating that sevoflurane exposure enhances endothelial progenitor cell mobilization and recruitment in the infarcted myocardium, an event that accounts for part of the cardioprotective effect of delayed anesthetic preconditioning.Methods
The experiments were performed on Wistar rats (n = 36) randomly assigned to a control and a preconditioned group. The rodents were intubated and ventilated with room air for the control group and with 1 MAC sevoflurane for the preconditioned group. Luminex was used to evaluate the plasma levels of VEGF and G-CSF, whereas the mobilization of CD 34 + / flk-1 + progenitor cells in the peripheral blood was estimated by flow cytometry and immunofluorescence. The level of progenitor cells (c-kit + ) present in the injured myocardium was measured through immunofluorescence one day after the ischemia-reperfusion lesion in similar experimental groups (n = 18). The cardioprotection was assessed through apoptosis assays (one day after ischemia/ reperfusion injury) and by measuring the area of fibrosis (2 weeks after ischemia/ reperfusion injury).Results
Increased levels of VEGF and G-CSF were recorded at 3 and 6 h respectively after sevoflurane exposure, followed by a rise in CD34 + / flk-1 + cells beginning at 12 hours after preconditioning, compared to the control group, with a maximum level at 24 hours after exposure to sevoflurane (p < 0.05). The number of c-kit + cells in the myocardial area damaged after the ischemia/ reperfusion procedure was significantly increased (p=0.001), the degree of apoptosis was reduced (p=0.007) and the area of fibrosis was diminished (p < 0.05) in the late preconditioned group compared to the control group.Conclusions
Our results indicate for the first time the mobilization of a population of mononuclear cells, with endothelial progenitor cell markers (CD 34, flk-1) in the late phase of anesthetic preconditioning. These cells are a potential source of endothelial repair and myocardial regeneration in the context of perioperative or periprocedural ischemia in patients with coronary artery disease.