Effects Of Aminocaproic Acid And Ulinastatin On Fibrinolytic System And Inflammatory Response To Cardiopulmonary Bypass In Cardiac Valve Replacement Surgery

Objectives To investigate the effects of epsilon amidocaproic acid and ulinastatin on hyperfibrinolysis and inflammatory response resulting from cardiopulmonary bypass(CPB) in cardiac valve replacement surgery.Methods Sixty patients scheduled for elective cardiac valve replacement with CPB were randomly divided into four groups of 15 each:control group(C), epsilon amidocaproic acid group(E),ulinastatin group(U) and drug combination group(D).With the same anesthesia,cardiopulmonary bypass and myocardial preservation,group E received epsilon amidocaproic acid bolus 150mg/kg followed by an infusion at 15mg/(kg·h),group U received ulinastatin 1.2×10⁴U/kg, group D received epsilon amidocaproic acid combined with ulinastatin,group C received an equivalent volume of saline.Blood samples were taken from radial artery for determination of plasma D-dimer,t-PA,PAI-1,α₂-AP,NE,TNF-α, IL-6 and IL-10 concentrations before induction of anesthesia(T1),1 h after start of CPB(T2),1 h(T3) and 24 h(T4) after termination of CPB.Except for D-dimer, these parameters were estimated by enzyme-linked immunosorbent assay(ELISA). The postoperative drainage volumes were measured in the duration of the 6hours, 12hours and 24hours after surgery.Criteria for the transfusion of blood products were standardized and transfusion amounts were recorded.The time for endotracheal extubation and the ICU stay were recorded and compared.Results1.There was no significant difference in the four groups in plasma D-dimer, t-PA,PAI-1 andα₂-AP levels at T1.The levels of D-dimer and t-PA were significantly increased at both T2 and T3 compared with that before CPB(T1) in all groups.However,the plasma concentrations of D-dimer and t-PA were significantly lower in group E and D than those in group C at T2 and T3.The plasma concentration of PAI-1 was significantly elevated at T3 compared with that at T1 in all groups,and there was no significant difference among the four groups.The levels ofα₂-AP were significantly increased at T2 in all groups and at T3 in group E,U and D compared with the levels at T1.AT T3 point,the plasma concentrations ofα₂-AP in group E and D were significantly higher than those in group C.2.The postoperative drainage volume/BSA in group E and D within 6 h,12h and 24h were significantly lower than those in group C.3.The proportion of patients requiring blood transfusion and the average consumption of packed red blood cell were similar in all groups.4.The level of NE was significantly increased at T2 and T3 and the levels of TNF-α,IL-6 and IL-10 were significantly increased at T2,T3 and T4 in all groups. The plasma concentrations of NE,TNF-αand IL-6 were significantly lower while the concentration of IL-10 was signifcantly higher in group U and D than those in group C at T2,T3 and T4.The plasma concentration of NE was significantly lower in group E than that in group C at T2 and T3 and the concentrations of TNF-αand IL-6 was significantly lower in group E than those in group C at T3.5.The time for endotracheal extubation and ICU stay were similar among the four groups.Conclusions1.Prophylactic administration of EACA can inhibit the CPB-induced D-dimer formation and t-PA release,and enhance theα₂-AP release.EACA is effective in suppressing hyperfibrinolysis and reducing blood loss.Moreover, EACA suppresses the release of NE,TNF-αand IL-6 during CPB.2.Ulinastatin can reduce the increased amplitude of plasma levels of NE, TNF-αand IL-6,whereas enhance the increased amplitude of the plasma IL-10 levels that result from CPB in cardiac valve replacement.In other word, ulinastatin posseses the effect to regulate inflammatory cytokines balance and down-regulate inflammatory response during CPB.However,Ulinastatin has no effect on hyperfibrinolysis and hemorrhage resulting from CPB.3.EACA combined with ulinastatin can suppress hyperfibrinolysis,decrease inflammatory response and reduce postoperative blood loss in patients undergoing cardiopulmonary bypass,which maybe result in better clinical outcomes.