左西孟旦、米力农和硝普钠治疗急性心力衰竭的对比研究

  本文关键词：左西孟旦、米力农和硝普钠治疗急性心力衰竭的对比研究，由笔耕文化传播整理发布。

        研究背景：急性心力衰竭(Acute Heart Failure，AHF)患者中约15％-20％为首诊心衰，大部分则为原有的心衰加重。既往研究证实，传统的非洋地黄类正性肌力药，因可以增加心肌耗氧量，诱发心律失常，会增加患者的死亡率及再住院率，使其在临床上的应用受到限制。左西孟旦（levosimendan，LEV）作为一种新型的钙离子增敏剂，与心肌细胞细肌丝上肌钙蛋白C(cTnC)结合，增加心肌收缩力，但不增加心肌氧耗，从而发挥正性肌力作用。2005年欧洲心脏病协会关于心力衰竭的治疗指南也建议无低血压和血容量不足的心力衰竭患者选用左西孟旦治疗。左西孟旦治疗急性心力衰竭的主要作用机制有（：1）收缩期选择性增加cTnC对Ca2+的敏感性，但不影响细胞内Ca2+浓度，舒张期细胞内Ca2+浓度恢复正常，这使得该药不引起心肌耗氧量增加或细胞内钙超载，具有正性肌力作用而没有舒张功能的损伤；（2）使心肌细胞和血管平滑肌细胞K+通道开放，引起心肌细胞动作电位时程缩短，血管平滑肌细胞超极化，抑制钙离子内流，直接扩张冠状动脉和外周血管，使心肌血流量增加，并且减少心脏前、后负荷，增加每搏量和心输出量，而心率和心肌耗氧量不增加，从而发挥心肌保护机制；（3）降低心力衰竭患者血清脑利钠钛(BNP)、肿瘤坏死因子（TNF-α）、白介素-6(IL-6)，以及内皮素-1（ET-1）的水平，抑制心衰患者交感神经内分泌系统的激活，抗炎、抗氧化以及对抗心肌细胞凋亡，通过多种途径阻断心肌结构重塑，改善预后。目的：通过比较左西孟旦、米力农和硝普钠治疗急性心力衰竭患者前后的临床疗效，左室舒张末内径（LVIDd）、左室射血分数（LVEF）和短轴缩短率（FS）的变化，血清氨基末端B型利钠肽前体（NT-proBNP）、内皮素-1（ET-1）、去甲肾上腺素(NE)水平变化及临床安全性，观察左西孟旦对AHF患者临床症状，心脏收缩功能，神经内分泌系统的影响，为左西孟旦治疗AHF患者提供理论依据。方法：选择急性心力衰竭患者90例，随机分为左西孟旦组、米力农组和硝普钠组各30例，所有研究对象均于用药前、用药后24h、用药后7d抽取肘静脉血，立即离心分离血清，置于-70℃冰箱保存待测。采用酶联免疫吸附测定(Enzyme-linked immune sorbent assay，ELISA)法，测定三组患者血清NT-proBNP、ET-1和NE含量。由固定医师操作，对所有对象在治疗前和治疗后7d进行心脏彩色多普勒超声心动仪检查，比较左西孟旦、米力农和硝普钠对AHF患者的LVIDd、LVEF、FS的影响。结果：（1）三组治疗后24h的血压与治疗前比较无统计学差异，而治疗后24h的心率与治疗前比较降低（P<0.05），但三组间比较无统计学差异。（2）治疗后24h，左西孟旦组较其他两组总有效率高（P=0.004、0.015），有统计学差异，左西孟旦组患者临床状况显著改善。（3）治疗后7d，三组患者LVIDd、LVEF及FS均较治疗前改善（P<0.01），左西孟旦组LVIDd与其他两组比较未见缩小（P=0.113），而LVEF、FS较其他两组增加（P<0.01），有统计学差异。（4）三组治疗后24h及7d血清NT-proBNP水平均较基线水平降低（P<0.01），，治疗后7d较治疗后24h进一步降低（P<0.01），左西孟旦组治疗后7d血清NT-proBNP水平比其他两组降低（P=0.006、0.003），有统计学差异。三组治疗后7d血清ET-1和NE水平较基线水平降低（P<0.01），治疗后7d左西孟旦组血清NE比其他两组降低更多（P<0.017）。（5）随访三月，左西孟旦组再住院率明显低于其他两组（P=0.005、0.013），有统计学差异。（6）左西孟旦组比硝普钠组不良反应发生率低（P=0.01），与米力农组比较无统计学差异（P=0.038）。结论：（1）左西孟旦能明显改善AHF患者呼吸困难及全身临床症状，缩小LVIDd，提高LVEF和FS，从而改善心脏收缩功能。（2）左西孟旦抑制AHF患者神经内分泌系统的激活，降低血清中NT-proBNP、ET-1和NE水平，阻断心肌结构重塑，对心脏起到保护作用，并且能够降低近期再住院率，不良反应少，安全性高。

    Background: About15%-20%patients with acute heart failure areconfirmed for the first time, most of them are the aggravating original failure.Previous studies confirmed that clinical application of traditional non digitalispositive inotropic drugs was limited, because of increasing myocardial oxygendemand, inducing arrhythmias and adding the patients’ mortality and rehospitalizationrate. Levosimendan as a new calcium sensitizer can combine with myocardial cellthin myofilament troponin C(cTnC), improve the myocardial contraction function,without increasing myocardial oxygen demand, so it has the positive inotropic effect.The European Heart Association for the guidelines of2005on the diagnosis andtreatment of acute heart failure also recommend that heart failure patients without lowblood pressure and hypovolemia can choose leosimendan.Leosimendan has several main mechanisms of action about treatment of acuteheart failure.(1)It has selective sensitization of calcium ion for troponin C,myocardial contraction does not affect intracellular calcium concentration, whichrecovers normal level after systole. Thus it doesn’t increase myocardial oxygendemand, or intracellular calcium overload, thereby it has positive inotropic effect andno damage of diastolic function;(2)It makes potassium channels of myocardial cellsand vascular smooth muscle cells open and shortens action potential duration ofmyocardial cells, occurs hyperpolarization of vascular smooth muscle cells, reducesthe inflow of calcium, which expands coronary arteries and peripheral vessels, so itcan protect the heart against myocardial ischemia, accordingly decreases pro load andpost load of heart, and makes the stroke volume and cardiac output increase, withoutheart rate and myocardial oxygen demand increasing, so as to play a role asmyocardial protection;(3)Leosimendan reduces serum levels of brain natriuretictitanium (BNP),tumor necrosis factor alpha（TNF-α）,interleukin6(IL-6) and endothelin1(ET-1) in patients with heart failure, inhibiting the activation ofsympathetic neuroendocrine system, reducing inflammation and oxidation, therebydecreasing myocardial cellular death and apoptosis, and blocking myocardialremodeling through various ways, which has a favorable impact on prognosis.Objective: Compare that levosimendan can obviously improve clinicalsymptoms and cardiac systolic function in patients with acute heart failure(AHF),control the activation of neuroendocrine system, reduce rehospitalization rate andhave high safety. Observe the clinical effects, the changes of left ventricular internaldiameter at end-diastole (LVIDd), left ventricular ejection fraction(LVEF) andfractional shortening(FS), and the levels of B type natriuretic peptide precursor(NT-proBNP), endothelin1(ET-1) and norepinephrine(NE) before and after treatmentof levosimendan, milrinone and sodium nitroprusside.Methods: Selected90cases of hospitalized patients with acute heart failure,who were randomly divided into levosimendan group, milrinone group and sodiumnitroprusside group. Each group has30cases. Blood samples of all subjects weredrawn venous blood at baseline, and then24h and7d.Blood were immediatelycentrifuged and serum were stored frozen-70℃until analysis. Detectedconcenterations of NT-proBNP, ET-1and NE in the serum of all patients byenzyme-linked immunosorbent assay(ELISA). Operated by fixed doctors. All patientswere examined at baseline and7d by cardiac color Doppler ultrasound, thencompared LVIDd, LVEF and FS.Results:(1)There is no statistical difference in blood pressure betweenbaseline and24hours of treatment, and heart rate of treatment decrease comparingwith baseline(P<0.05), While there are no statistical differences in blood pressure andheart rate among there groups.(2)After24hours of treatment, total effective rate washigher in levosimendan group than other two groups(P=0.004,0.015). Patients’systemic clinical conditions of levosimendan group were improved markedly.(3)After7days of treatment, LVIDd, LVEF and FS of three groups were better thanbaseline(P<0.01). In levosimendan group, LVIDd was not reduced than other groups(P=0.113), but LVEF and FS were increased(P<0.01).(4)In three groups,serum NT-proBNP levels decreased24hours and7days after treatment thanbaseline(P<0.01), and the level furtherly reduced7days after treatment than24hours(P<0.01). After7days treatment, serum NT-proBNP of levosimendan groupreduced markedly than other groups (P=0.006,0.003). Serum ET-1and NE levels ofthree groups7days after treatment reduced than baseline (P<0.01).After7daystreatment, serum NE of levosimendan group reduced markedly than othergroups(P<0.017).(5)Followed up three months, in levosimendan group,rehospitalization rate was significantly lower than other groups (P=0.005,0.013).(6)Incidence rate of adverse reactions in levosimendan group is lower than sodiumnitroprusside group(P=0.01). There is no statistical difference between levosimendangroup and milrinone group(P=0.038).Conclusions:(1)Levosimendan can significantly improve dyspnea andclinical symptoms, reduce LVIDd, with increasing LVEF and FS in patients withAHF;(2)Leosimendan restrains the activation of neuroendocrine system, and reducesserum levels of NT-proBNP, ET-1and NE in patients with acute heart failure, withblocking myocardial remodeling. It has protection and high security for cardiac.Thereby reduce recent rehospitalization rate. Adverse reactions are low.

左西孟旦、米力农和硝普钠治疗急性心力衰竭的对比研究

摘要5-8Abstract8-10缩略词表11-12前言12-14对象与方法14-19结果19-23讨论23-25结论25-26参考文献26-28综述28-35    参考文献32-35作者简介35-36致谢36

  本文关键词：左西孟旦、米力农和硝普钠治疗急性心力衰竭的对比研究，由笔耕文化传播整理发布。