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左西孟旦乌司他丁与其联合用药对幼兔离体心脏的保护作用

Protective effects of levosimendan and ulinastain on the isolated rabbit heart

摘要目的 通过幼兔离体心脏Langendorff模型,探讨左西孟旦、乌司他丁及二者联合应用对幼兔离体心脏缺血再灌注损伤的保护作用.方法 建立新西兰幼兔离体心Langendorff模型,经左心房、二尖瓣置入左室测压管.K-H液平衡灌注10 min,分别用K-H液(C组)、乌司他丁5万单位/kg(U组)、小剂量左西孟旦0.1 μmoL/L(L1组)、大剂量左西孟旦0.3 μmol/L(L2 组)、乌司他丁5万单位/kg和左西孟旦0.1 μmol/L(L+U组)灌注10 min.应用St.Thomas停跳液使心脏停跳,全心缺血30 min,然后分别以上述液体复灌30 min.于缺血前和复灌即刻、10 min、20 min、30 min记录心率(HR)、左室内压(LVP)、左室内压最大上升速率(LVdp/dt)、冠脉流量(CF);同时测定冠状静脉流出液中肌酸激酶(CK)、肌钙蛋白(cTnI)、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)的浓度.结果 L1 组、L2组和L+U组复灌后LVP、LVdp/dt与对照组(C组)和U组差异有统计学意义,但L2组的心率明显高于其他组.与其他各组比较,左西孟旦和乌司他丁联合用药组复灌后冠脉流量(CF)升高(P<0.05);冠状静脉流出液CK、cTnI,TNF-α、IL-6的浓度明显低于其他组.结论 左西孟旦和乌司他丁通过不同机制均能较好地减轻幼兔心肌缺血再灌注损伤,其联合用药对未成熟心肌的保护作用强于单独应用.

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abstractsObjective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery.The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I/R) injury to the isolated immature rabbit hearts and investigate the possible mechanism.Methods Fifty New Zealand long-ear white immature rabbits were anesthetized and heparinized.Their hearts were rapidly removed and mounted on modified Langendorff apparatus.A left ventricle pressure monitoring line was inserted through the left atrial and mitral valve.The hearts were equilibrated with oxygenated K-H solution at 37℃ for 10 minutes.The rabbit hearts were randomly divided into 5 groups with 10 hearts in each group.Hearts in group C were perfused with K-H solution,in group U were perfused with ulinastain (50000 U/kg),in group LI were perfused with Levosimendan 0.1 μmol/L,in group L2 were perfused with Levosimendan 0.3 μmol/L,and in group L + U were perfused with Ulinastain (50 000 U/kg) and Levosimendan 0.1μmol/L.The hearts were arrested with St-Thomas solution for 30 min.Hearts in each group underwent 30 min-reperfusion with the same solutions after 30 min-global myocardial ischemia.Heart rate ( HR) Jeft ventricular pressure ( LVP) and LVdp/dtMax were monitored.Effluent from coronary sinus was collected at time of ischemia /reperfusion for measuring the concentration of TNF-α,IL-6,CK and cTnI.Results LVP and LVdp/dt in group L1,L2 and L + U were better than those in group C and U.But the heart rates in group L2 were higher than in other groups.Concentrations of CK,cTnI,TNF-α and IL-6 in the effluent from coronary sinus at 0、10 and 30 min of reperfusion were significantly lower in group L + U than in the other groups.Conclusion Levosimendan may have the similar effects with ulinastain in reducing the reperfusion injury to the immature myocardium.The protective effect of levosimendan (0.1 μmol/L) in combination with ulinastain (50 000 U/kg) was better than that of levosimendan or ulinastain alone.

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