乌司他丁联合1,6二磷酸果糖对心内直视手术体外循环心肌保护的研究

The research of ulinastatin combined with fructose-1,6-diphosphate on open-heart operation of myocardial protection during cardiopulmonary bypass

目的探讨不同剂量乌司他丁和1,6二磷酸果糖对体外循环后心肌损伤的保护效果及其合适剂量,为药物心肌保护提供理论基础和临床依据。方法选择60例(NYHA II～III级)择期在体外循环下行心内直视手术的先天性心脏病或心脏瓣膜病病人,随机分为实验1组(U1+F1)、实验2组(U2+F2)和对照组(C),每组20例。实验1组(U1+F1)将乌司他丁(50万U)加入预充液中+1,6二磷酸果糖(5g)于主动脉开放后快速静脉滴注(2min);实验2组(U2+F2):将乌司他丁(100万U)加入预充液中+1,6二磷酸果糖(10g)于主动脉开放后快速静脉滴注(2 min);对照组(C组)以等量生理盐水替代,给药方法同上。三组于围术期不同时点(T1一麻醉后切皮前;T2一主动脉开放后30min;T3一停体外循环4小时;T4一停体外循环12小时;T5一停体外循环24小时。)经中心静脉采血检测心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDHI)。临床观察CPB时间、主动脉阻断时间、心脏自动复跳情况、平均除颤次数、心电图S-T段改变、正性肌力药用量等项目。结果三组病人Tl时点血浆LDHl和CK-MB、cTnI的浓度均在正常范围之内,组间比较无差异(P>0.05)。在主动脉开放后的4个时点(T2、T3、T4、T5)的血浆LDHI、CK-MB、cTnI浓度与T1时点比较均显著升高(P<0.05)。实验1组(U1+F1),2组(U2+F2)cTnI、CK-MB于T2(开放升主动脉后30 min)显著低于对照组(P<0.05),U1+F1组血浆cTnI、CK-MB浓度在T5时点显著低于c组(P<0.01);U2+F2组在T4点血浆cTnI、CK-MB浓度即显著低于c组(P<0.01),在T5时点已回落到基本正常范围。C组血浆LDHl浓度在CPB后各时点均升高,于T5时点仍呈继续升高趋势;U1+F1组血浆LDHl浓度在主动脉开放后亦升高,但升高幅度低于C组(P>0.05),基本处于维持状态;U2+F2组于T2时血浆LDHI浓度达到高峰,此后逐渐降低,于T5时点显著降低(P<0.01),其浓度已接近正常范围。与对照组(C组)比较实验1组(U1+F1),2组(U2+F2)心脏自动复跳率高、术中S-T段改变轻微、正性肌力药用量少。结论乌司他丁和1,6-二磷酸果糖在心脏直视手术体外循环中具有良好的心肌保护作用,且其心肌保护作用随剂量的增大而呈正相关。

Objective： To discuss different doses of ulinastatin and fructose-1,6-diphosphate on myocardial injury after cardiopulmonary bypass protection effect and suitable the drug dose,and to provide theoretical basis and clinical evidence on myocardial protection of the drug.Methods： Sixty patients（NYHA II～III）,who were elective in cardiopulmonary bypass open-heart operation of congenital heart disease or valvular heart disease patients,were randomly divided into the experimental group 1（U1＋F1）,the experimental group 2（U2＋F2） and the control group（C）,with 20 cases for each.The experimental group 1（U1＋F1） had the ulinastatin（0.5million U） into the priming solution ＋ the fructose-1,6-diphosphate（5 g） was given rapidly intravenous（2 min） after the opening of the aortic.The experimental group 2（U2＋F2） had the ulinastatin（1million U） into the priming solution ＋ the fructose-1,6-diphosphate（10 g） was given rapidly intravenous（2 min） after the opening of the aortic.As compared with the experimental group,the same volume of normal saline was given into the patients in the control group.The cardiac troponin I（cTnI）,creatine kinase MB isoenzyme（CK-MB）,lactate dehydrogenase（LDHI） were measured at different time points（T1-after anesthesia,before skin incision;T2-at 30min after the opening of the aortic;T3-at 4hr after the termination of CPB;T4-at 12hr after the termination of CPB;T5-at 24hr after the termination of CPB） in the three groups by central venous blood sample.Clinical observation included the CPB time,aortic cross-clamp time,automatic cardioversion,average number of ECG defibrillation,ST segment,positive inotropic drug dosage and other projects.Results： The plasma levels of LDHl and CK-MB,cTnI were within normal ranges and there was no significant difference measured among three groups at T1（P〈0.05）.At 4 time（T2,T3,T4,T5） after the opening of the aortic,the plasma concentration of LDHI,CK-MB,cTnI concentrations were significantly increased compared with those at T1 time（P〈0.01）.At T2 time the concentration of cTnI,CK-MB in the experimental group 1 and group 2 was significantly lower than that in the control group（P〈0.01）.At T5 time the concentration of cTnI,CK-MB in the experimental was significantly lower than that of the control group（P〈0.01）;In group 2 the concentration of CK-MB and cTnI was significantly lower than that of the control group at T4 time（P〈0.01）.However at T5 time the concentration dropped to the normal range.After the CPB in Group C the concentration of LDHl was increased at each point,at T5 the concentration continued to show a rising trend;After the opening of the aortic in Group 1 the plasma concentration of LDHl also increased,but the increasing amplitude was lower than that in the control group（P〈0.05）.It was maintained basicly;At T2 time in group 2 the plasma level of LDHI reached the peak,then decreasedgradually,its concentration was decreased significantly and close to the normal range at T5 time（P〈0.01）.Compared with the control group,the experimental group 1,group 2 had highly the automatic cardioversion rate,changed at ST-segment slightly during the operation,decreased the dose of positive inotropic drug.Conclusion： The myocardial protection during cardiopulmonary bypass has better effect by ulinastatin combined with fructose-1,6-diphosphate on open-heart operation,indicating its myocardial protection is dose-dependent.