Effect Of Sevoflurane Preconditioning On Nrf2 Protein Expression In Peripheral Blood Mononuclear Cells And Myocardial Anti-oxidative Stress Of The Patients Undergoing Cardiac Valve Replacement

Objective:Cardiopulmonary bypass(CPB) can lead to the body organ ischemia and reperfusion injury. Sevoflurane is a commonly used inhaled anesthetics, has myocardial protective effect, while the mechanism is not yet fully elucidated. However, oxidative stress is one of the mechanisms of ischemia reperfusion injury. Nuclear factor erythroid 2-related factor 2(Nrf2) is in the key position of antioxidative stress. The detection in the monocytes of Nrf2 expression, indexs of serum myocardial injury and observing the clinical indicators, to evaluate the effect of sevoflurane pretreatment of CPB in patients with the peripheral blood mononuclear cells of Nrf2 expression and myocardial anti-oxidative stress, It can provide some reference for the mechanism to study the protective effect of sevoflurane on myocardial.Methods:In this randomized controlled trial,40 eligible patients were divided into one of two groups(n=20 each):control group(group C) and sevoflurane preconditing group(group S). In group S,1.0% sevoflurane was inhaled for 20 min from skin incision, and followed oxygen elution for 10 min, repeated two cycles. While in group C, the patient inhaled only 100% O2. After entering the operating room, all the patient were conventional monitored with ECQ HR, SpO2, IBP, T, NTI and so on. Intravenous anesthesia induction medicine are midazolam 0.08～0.15 mg/kg, etomidate 0.2～0.4 mg/kg, sufentanil 0.5～0.8 μg/kg, rocuronium 0.6～1 mg/kg. Circulation must be maintained stable during anesthesia induction. After anesthesia induction, patients in two groups were continually ventilated mechanically (Oxygen flow rate:2-3L/min, ⅤT: 6-10 ml/kg, RR:12-15 b/min, I:E 1:1.5～2). Central venous pressure (CVP) were monitored by right internal jugular vein catheterization. Left ventricular function was monitored by the mouth into the esophagus ultrasonic Doppler probe. CPB were made up of Jostra HL20 heart-lung machine and Maquet membrane oxygenate. After the surgery, patients were send to intensive care unit (ICU). The artery blood samples were collected for the measurements of serum concentration of cTnI, MDA and SOD immediately before anesthesia induction(T1), at 2h(T2),24h(T3) and 48h(T4) after aorta declamping respectively. The nulear protein were obtained from PBMC to determine the expression of Nrf2 protein by Western Blot. Record the HR, MAP, stroke volume (SV)and cardiac index (CI) before cutting the skin,30 min after CPB and the end of surgery. Record clinical indexes, such as time of aorta blocking and CPB, the left ventricular ejection fraction (LVEF) in one week after the surgery, and so on.Results:In two groups, general data and characteristics of all patients during operation were not considerable change at all time points(P>0.05). Comparing with before operation, serum cTnI increased significantly in both groups(P<0.05) at T2～4 after aorta-declamping. However, it was much lower in group S than group C((P<0.05). The serum MDA concentration was decreased, while SOD activity was significantly higher at T2～4 in group S, the difference were statistically significant(P<0.05). Nrf2 protein content in PBMC increased significantly in both groups 24h after reperfusion compared with before operation. However, it was much higher in group S than group C(P<0.05). Before cutting the skin, the two group of patients with HR, MAP, SV and CI comparative differences had no statistical significance. At 30 min after CPB and the end of surgery, MAP, SV and CI were higher in group S than group C(P<0.05), but HR had no statistical significance in two groups. LVEF were decreased in both groups one week after the surgery compared with before operation, however, it was much higher in group S than group C(P<0.05). Compared with group C, in group S the dosage of dopamine and dobutamine were reduced (P<0.05), the time of ICU residence, mechanical ventilation, and the actual length of stay were shortened (P<0.05), while there were no difference between the rate of heart beating automatically and cases of adrenaline using among two groups (P>0.05).Conclusion:In summary, sevoflurane preconditioning can alleviate myocardial injury and reduce oxidative stress injury in patients undergoing cardiac valve replacement with CPB, which might be associated with increasing Nrf2 expression. This can investigate the protective mechanism of sevoflurane provided a degree of reference.