The Effects Of Ulinastatin On Inflammatory Cytokines, S100β Protein And Early Post-operative Cognitive Dysfunction 0f Patients Undergoing Cardiac Combined Valve Replacement Surgery

Objective: To observe the effects of ulinastatin on S100β protein, inflammatory cytokine interleukin 6(IL-6), anti-inflammatory cytokines IL-10 and early post-operative cognitive function of the patients undergoing cardiac combined valve replacement surgery with cardiopulmonary bypass(CPB).To explore the effect of ulinastatin on brain injury and mechanism on brain protection.Methods: 40 patients who were undergoing cardiac combined valve replacement surgery(combined mitral valve replacement with aortic valve replacement)in our hospital,whose heart function were class II-III according to the NYHA classification standard heart function,were randomly divided into experimental group and control group, n=20. Adopt intravenous inhalation anesthesia. The patients of experimental group received ulinastatin 12000U/kg before incision by intravenously pumping,6000U/kg ulinastatin was added to the priming solution,and 6000U/kg ulinastatin was given before 5min of the aortic decamping.The patients of control group were given equal volume of physiological saline. Jugular bulb blood of each group were drew off before administration of anesthesia induction(T1), 30 min after CPB(T2), 30 min after the end of CPB(T3),3h after the end of operation(T4), 6h after the end of operation(T5),and 24 h after the end of operation(T6). Serum concentration of IL-6﹑IL-10 and S100β protein were measured by ELISA. Patients were investigated by using mini mental state examination(MMSE) in 1 days before operation,2 day after operation and 7 day after operation to determine whether the POCD occurred.Results: The concentration of IL-6,IL-10 and S100β protein in plasma of the two groups were changed with time, which was the lowest in T1, and reached peak value at T3 after increased gradually,then decreased gradually. Compared with control group, the concentration of the IL-6 and S100β protein was lower in T2- T6 point ofexperimental group(P<0.05), and the increased range of the concentration of the IL-6 and S100β protein in experimental group was lower than the control group.The concentration of IL-10 in experimental group was significantly higher than control group(P <0.05) and the increased range of the concentration of the plasma IL-10 in experimental group was higher than the control group(P <0.05).The incidence of POCD in experimental group was 15%(3 cases).The incidence of POCD in control group is 45%(9 cases). The incidence of POCD experimental group was significantly lower than that of control group with statistical difference(P <0.05). The concentration of S100β protein in the POCD cases was significantly higher than that in non POCD cases with statistical difference(P <0.05).Conclusion: The cardiac combined valve replacement surgery can trigger the inflammatory response,and cause increased levels of inflammatory cytokines such as IL-6,IL-10. The inflammatory reaction has involved in the process of brain damage. The elevated level of postoperative S100β protein had positive correlation with the occurrence of the early POCD. S100β protein can be a predictive indicator of the brain injury. The applications of the ulinastatin can reduce the incidence of early POCD. Because it can reduce the proinflammatory cytokine(IL-6) release, while promoting anti-inflammatory cytokine(IL-10) secretion. So it can inhibit inflammatory reaction.It can provide a reference for the clinical medicine of cardiac surgery. But whether the effect of the larger dose of ulinastatin on brain injury is better and whether ulinastatin can reduce the incidence of long-term POCD,it needs the further prolonged analysis of the large sample size.