兔常温体外循环中大剂量乌司他丁对凝血和纤溶系统的影响

Effect of Large Dose of Ulinastatin on Coagulation-Fibrinolysis System during Normothermia Extracorporeal Circulation in Rabbits

目的观察兔常温体外循环（extracorporeal circulation，ECC）前应用大剂量乌司他丁对凝血和纤溶系统的影响。方法20只大耳白兔随机分成2组：乌司他丁组（U组，n=10）和对照组（C组，n=10）。建立兔常温ECC模型，U组在ECC前给予乌司他丁10×10^4U／kg，C组给予等量生理盐水。ECC转机30min，流量为180～300ml／min，肛温维持在36．5℃-37．5℃。分别记录ECC前、停机、停机后1h、2h和3h的血流动力学指标，测定活化部分凝血激酶时间（Am）、凝血酶原时间（PT）、纤维蛋白原（FIB）和D二聚体（D—D）。结果两组PTECC后均较ECC前显著延长（P〈0．05），两组间胛在停机后3h时有统计学差别，C组长于U组（P〈0．05）。两组APTT ECC后也均较ECC前显著延长（P〈0．01），同时间点U组APTT较C组延长更为明显（P〈0．05）。两组血浆FIB含量ECC后均较ECC前显著降低（P〈0．01），同时间点C组较U组下降更明显（P〈0．05）。ECC后两组血浆D—D浓度较ECC前显著升高（P〈0．05），同时间点C组D—D浓度升高较U组更为显著（P〈0．05）。结论ECC后凝血因子消耗使APTr和Prr延长，纤溶亢进使血浆FIB含量下降，DD浓度升高。ECC前应用大剂量乌司他丁可减少ECC中凝血因子的消耗，抑制纤溶系统的过度激活，改善ECC术后凝血功能。提示ECC前应用大剂量乌司他丁具有血液保护功能。

OBJECTIVE To investigate the effect of large dose of ulinastatin on coagulation - fibrinolysis system after extracorporeal circulation（ECC） by establishing the rabbit model of normothermia ECC. METHODS Twenty rabbits were randomly assigned to control group （Group C, n = 10 ） and experiment group （Group U, n = 1Q）. The rabbits in Group U were administered ulinastatin 10 × 10^4 U/kg before ECC, while in Group C were received same volume of saline at the same time. All rabbits were undergoing ECC for 30 min at perfusion flow of 180 -300 ml/min, with rectal temper- ature maintained from 36.5℃ to 37.5℃. Hemodynamic parameters were recorded before ECC, at termination of ECC, 1 hour, 2 hour and 3 hour after ECC. APTT, PT, FIB and D - dimer were determined at the above time point respectively. RESULTS APTTs were prolonged after ECC in both Group U and C （ P 〈 0.05 ） , but APTTs after ECC in Group U were significantly longer than those in Group C respectively（ P 〈 0.05 ）. PTs were prolonged after ECC in both Group U and C（ P 〈0.05）. There was significant difference in PTs between Group U and Group C at 4 h after ECC. The latter was significantly longer than the former（ P 〈 0.05 ）. All levels of FIB in both Group U and C were decreased after ECC （ P 〈 0.05 ）, and the levels of FIB after ECC in Group U were obviously higher than those in group C respectively （ P 〈0. 05）. All concentrations of D - dimer in both Group U and C were increased after ECC （ P 〈 0. 05）,but the concentrations of D - dimer after ECC in Group U were substantially lower than those in Group C respectively（ P 〈 0.05）. CONCLUSION Over consumption of blood coagulation factors during ECC results in prolonged APTT and PT. Hyperfibrinolysis decreases levels of FIB, increases concentrations of D - D. Administration of large dose of ulinastatin before ECC can reduce the consumption of blood coagulation factors during ECC, inhibit excessive activation of fibrinolysis system, and subsequently promote coagulation after ECC. It suggests that large dose of ulinastatin may have blood protection effect.