Impact And Clinical Significance Of Ulinastain On Inflammatory Mediator HMGB1 And Others During Cardiopulmonary Bypass

Objective:To investigate changes in HMGB1 and TNF-alpha levels, clinical significance and their relationship during cardiopulmonary bypass perioperative period.Meanwhile,we identify the hypothesis that HMGB1 is a key pro-inflammatory cytokine;mechanism and impact of Ulinastain protective effects during CPB perioperative period were also investigated.Methods:72 cases of ASA gradeⅡ-Ⅳ(without significant hepatic or renal dysfunction) undergoing cardiac valve replacement under CPB were randomly chosen for this trial.EACA were used in control group(36 cases) by following way:10g EACA was added to priming solution; 30mg DXM(dexamethasone) was used during CPB process.Another 10g EACA after CPB without any other protease inhibitor or ultrafiltrtation was added to patients after procedure.In therapeutic group(36 cases),we used 30wu ulinastain with EACA before procedure and 20wu ulinastain was consistently used after procedure by intravenous drip for 3 days.In CPB process,foaming type artificial lung was used in all cases.Some venous blood samples were collected before operation(after anesthetized) (T1),before aortic cross-clamp(T2),after CPB(T3),and on the first day of postoperative between 6 and 7 a.m.(T4),as well as on 6 a.m.and 7 a.m.of second day(T5) and third day(T6) after operation.All supernatants of blood samples were centrifuged and frozen in -70℃to test high-mobility group box 1 protein(HMGB1),tumor necrosis factor alpha(TNF-α),alanine aminotransferase(ALT),creatinine(Cr) and serum urea nitrogen(BUN).Other parts of venous blood samples were sent for blood routine test.Cleaning middle urine samples that collected at same time point were frozen in -70℃to test urinary NAG,Cr andβ2-microglobulin(β2-MG).In order to exclude dilution during CPB,all outcomes were corrected(corrected value=measured value×HCT before CPB/HCT on sample test points).Urine results were corrected by comparing to Cr ratio.Results:1.The serum levels of HMGB1 can be detected at T1,and gradually increased at beginning of CPB(T2) then reached the peak at T3. Serum level of HMGB1 decreased to lower levels(T4) than preoperative and increased again after T4.Level of HMGB1 lasted to third day after operation.This trend is showed in double-peak.2.Serum levels of TNF-αalso gradually increased after the beginning of CPB and reached the peak at T3.TNF-αdecreased after CPB and reach the lowest point.Serum levels of TNF-αincreased on third day after operation.Serum levels of TNF-αafter CPB were significantly increased before CPB(P＜0.05). 3.Serum ALT level consistent at high levels on first day and third day after operation without decrease.Serum ALT level were obviously significance than T1(P＜0.01).But its relationship with HMGB1 and TNF-αis not clear so far.4.Serum Cr and BUN level in all time points after CPB were higher than T1(P＜0.05),and peak value was showed on T4 and T5.5.Urine NAG/Cr and BMG/Cr ratio reached highest peak value on T3.Urine NAG/Cr ratio was positive correlated to HMGB1 (r=0.26,P＜0.01)6.Serum Cr level,urine NAG/Cr ratio and urine BMG/Cr ratio might all positive correlated to serum TNF-αlevel,but correlation is not so obvious.7.Leukocyte count was increased on T3 and reached peak value on T5.Leukocyte counts were higher than T1 since T3(P＜0.01),and N%changing trend was almost same with WBC changing trend. Leukocyte count was positive correlated with N%changing trend (r=0.703,P＜0.01).8.There is no significance difference of HMGB1 between therapeutic and control group.9.All these above index except HMGB1 showed significance difference in therapeutic group than control group. Conclusions:1.HMGB1 was expressed in patients of rheumatic heart valve disease after anesthetization and before operation(heart function classⅡ-Ⅳ).2.HMGB1 was expressed obviously during CBP and after operation, in double-peak trend.3.Serum TNF-αlevel was one impact factor of renal function during perioperative period of CPB.4.Ulinastain can suppress systematic inflammatory reaction and protect renal function.But its impact on HMGB1 is not so clear during CPB perioperative period.