Effects Of Ulinastatin On Inflammatory Response To Cardiopulmonary Bypass In Infants And The Protective Effect On Lung Function

Objective:For the first time since1953,Gibbon has successfully appliedcardiopulmonary bypass technique in clinical extracorporeal circulation,makeit become an important supplementary means of cardiac surgical operation.With the constant improvement of cardiac surgical technique andextracorporeal circulation equipment technology,significantly reduce theextracorporeal circulation postoperative complications and mortality.However,in cardiopulmonary bypass,non-physiological perfusion, bloodcontact with non physiological material and ischemia reperfusion injurycaused systemic inflammatory.Systemic inflammatory have an importantinfluence on human body, especially the heart,lung,and kidney.Lung injury isa major complications under extracorporeal circulation operatio,and the deathof postoperative pulmonary complications of extracorporeal circulation take1/3percent of the total mortality after CPB. Ulinastatin (UTI) is a proteaseinhibitor extracted from the urine,developed by Japan in the80s,mainly for thetreatment of acute pancreatitis and acute circulatory failure.Domestic andforeign research found that Ulinastatin can inhibit the reaction ofinflammation,alleviate the lung injury,so as to protect the lung function.It hasbeen used clinically for the treatment of systemic inflammatory response,butnot many applications of UTI in pediatric extracorporeal circulationreports.This topic mainly through the determination of inflammatorycytokines(TNF-α, IL-2and IL-10)changes in plasma concentrations ofextracorporeal circulation in different time points,and monitoring pulmonaryfunction index of alveolar oxygenation index (OI), respiratory index (RI),toinvestigate the protective effects of ulinastatin on inflammatory responseduring cardiopulmonary bypass in infants and protective effect on lung injury. Methods:40patients with congenital heart disease undergoing cardiacoperation in infants and young children,were randomly divided intoexperimental group (20cases),control group (20cases),aged between1and6years,all the patients’ heart function, liver and kidney function beforeoperation is normal,without respiratory infection,without the use of hormonesand immune modulators etc.Using the same anesthesia method and operationsteps,ulinastatin group using20000u/kg dose, diluted with physiological salinesolution to10ml,before aortic intubation,half ulinastain was injected viaperipheral intravenous,the other half amount added into the liquid,withextracorporeal circulation turn into the body;the control group withsaline,usage.Respectively,before skin incision and after anesthesiainduction(T1),aortic open immediately (T2),4hour after shutdown (T3),24hour after shutdown (T4).Take the internal jugular vein blood3ml,3000r/mincentrifugal15min,take supernatant1.5ml inserted in EP pipes,tightly sealed,stored at-70℃refrigerator.Using Shenzhen Xin Sheng Bo biologicaltechnology company provides TNF-α, interleukin-2and interleukin-10humanELISA Kit, with enzyme-linked immunosorbent assay (ELISA) method todetect the serum TNF-α,IL-2, IL-10, in order to understand the inflammatoryresponse during CPB.Method for detection of respiratory function:Respectively,before skin incision and after anesthesia induction(T1),aorticopen immediately (T2),4hour after shutdown (T3),24hour after shutdown(T4),determination of inhaled oxygen concentration (FiO2)by breathingmachine;Determination of PaO2, PaCO2and hematocrit (Hct), according to theformula calculating oxygenation index (OI) and respiratory index (RI).Results:1.the concentration of two groups’ perioperative plasma of IL-2,IL-10and TNF-α in T2, T3, T4points were significantly higher than that inT1points (P <0.01); the concentration of plasma IL-2and TNF-α in T2, T3,T4time point in experimental group was significantly lower than the controlgroup (P<0.05); the concentration of plasma IL-10in T2, T3, T4time point inexperimental group significantly higher than control group (P<0.05).2.patients in the two groups of RI, OI have no significane in the T1point (P>0.05), after cardiopulmonary bypass T2~T4point compared withpreoperative T1time,RI value increased(P<0.05);OI values decreased(P<0.05).Compared with the control group,experimental group in T2~T4point,RI values decreased (P<0.05);OI values increased(P<0.05).Conclusion:1.This study observed two groups of patients in T2,T3,T4ateach time point,TNF-α, IL-2plasma concentrations were significantly higherthan that in group T1(P<0.01), suggesting that the extracorporeal circulationinevitably activated inflammatory cytokines;and plasma IL-10concentrationin T2,T3,T4time is significantly higher than the T1time (P<0.01),suggestingthat the large number of anti-inflammatory cytokines were produced afterCPB,the body’s own is also possible to limit inflammation, cause the body tosurvive. TNF-α, IL-2was significantly lower than that of control group(P<0.05), IL-10was significantly higher than that of the control group(P<0.05).Indicates that ulinastatin applied in CPB can inhibit the excessiverelease of pro-inflammatory cytokines TNF-α,also inhibit excessive secretionof immunomodulatory cytokines IL-2,at the same time can promoteanti-inflammatory cytokine IL-10,play a role in immune regulation,inhibitexcessive inflammatory reaction in patients with CPB operation,to maintainthe pro-inflammatory cytokines and anti-inflammatory cytokinesbalance,reduce the postoperative complications for the infants,Conducive tothe recovery of postoperative cardiopulmonary function in patients withinfants and young children.2. This study found that the two groups of patientsafter CPB,OI value decreased in different degree,RI value increased indifferent degree,which confirmed the presence of lung injury in CPB.AfterCPB,RI and OI in the experimental group were obviously improved than thecontrol group,after CPB the control group RI increased,OI decreased;Theexperimental group RI was significantly lower than the control group,OI wassignificantly higher than that of the control group.Prompt ulinastatin canimprove pulmonary oxygenation function,reduce lung injury caused by CPB,improve lung function.