本文關(guān)鍵詞：左西孟旦、米力農(nóng)和硝普鈉治療急性心力衰竭的對比研究，由筆耕文化傳播整理發(fā)布。

        研究背景：急性心力衰竭(Acute Heart Failure，AHF)患者中約15％-20％為首診心衰，大部分則為原有的心衰加重。既往研究證實，傳統(tǒng)的非洋地黃類正性肌力藥，因可以增加心肌耗氧量，誘發(fā)心律失常，會增加患者的死亡率及再住院率，使其在臨床上的應(yīng)用受到限制。左西孟旦（levosimendan，LEV）作為一種新型的鈣離子增敏劑，與心肌細(xì)胞細(xì)肌絲上肌鈣蛋白C(cTnC)結(jié)合，增加心肌收縮力，但不增加心肌氧耗，從而發(fā)揮正性肌力作用。2005年歐洲心臟病協(xié)會關(guān)于心力衰竭的治療指南也建議無低血壓和血容量不足的心力衰竭患者選用左西孟旦治療。左西孟旦治療急性心力衰竭的主要作用機制有（：1）收縮期選擇性增加cTnC對Ca2+的敏感性，但不影響細(xì)胞內(nèi)Ca2+濃度，舒張期細(xì)胞內(nèi)Ca2+濃度恢復(fù)正常，這使得該藥不引起心肌耗氧量增加或細(xì)胞內(nèi)鈣超載，具有正性肌力作用而沒有舒張功能的損傷；（2）使心肌細(xì)胞和血管平滑肌細(xì)胞K+通道開放，引起心肌細(xì)胞動作電位時程縮短，血管平滑肌細(xì)胞超極化，抑制鈣離子內(nèi)流，直接擴張冠狀動脈和外周血管，使心肌血流量增加，并且減少心臟前、后負(fù)荷，增加每搏量和心輸出量，而心率和心肌耗氧量不增加，從而發(fā)揮心肌保護機制；（3）降低心力衰竭患者血清腦利鈉鈦(BNP)、腫瘤壞死因子（TNF-α）、白介素-6(IL-6)，以及內(nèi)皮素-1（ET-1）的水平，抑制心衰患者交感神經(jīng)內(nèi)分泌系統(tǒng)的激活，抗炎、抗氧化以及對抗心肌細(xì)胞凋亡，通過多種途徑阻斷心肌結(jié)構(gòu)重塑，改善預(yù)后。目的：通過比較左西孟旦、米力農(nóng)和硝普鈉治療急性心力衰竭患者前后的臨床療效，左室舒張末內(nèi)徑（LVIDd）、左室射血分?jǐn)?shù)（LVEF）和短軸縮短率（FS）的變化，血清氨基末端B型利鈉肽前體（NT-proBNP）、內(nèi)皮素-1（ET-1）、去甲腎上腺素(NE)水平變化及臨床安全性，觀察左西孟旦對AHF患者臨床癥狀，心臟收縮功能，神經(jīng)內(nèi)分泌系統(tǒng)的影響，為左西孟旦治療AHF患者提供理論依據(jù)。方法：選擇急性心力衰竭患者90例，隨機分為左西孟旦組、米力農(nóng)組和硝普鈉組各30例，所有研究對象均于用藥前、用藥后24h、用藥后7d抽取肘靜脈血，立即離心分離血清，置于-70℃冰箱保存待測。采用酶聯(lián)免疫吸附測定(Enzyme-linked immune sorbent assay，ELISA)法，測定三組患者血清NT-proBNP、ET-1和NE含量。由固定醫(yī)師操作，對所有對象在治療前和治療后7d進行心臟彩色多普勒超聲心動儀檢查，比較左西孟旦、米力農(nóng)和硝普鈉對AHF患者的LVIDd、LVEF、FS的影響。結(jié)果：（1）三組治療后24h的血壓與治療前比較無統(tǒng)計學(xué)差異，而治療后24h的心率與治療前比較降低（P<0.05），但三組間比較無統(tǒng)計學(xué)差異。（2）治療后24h，左西孟旦組較其他兩組總有效率高（P=0.004、0.015），有統(tǒng)計學(xué)差異，左西孟旦組患者臨床狀況顯著改善。（3）治療后7d，三組患者LVIDd、LVEF及FS均較治療前改善（P<0.01），左西孟旦組LVIDd與其他兩組比較未見縮小（P=0.113），而LVEF、FS較其他兩組增加（P<0.01），有統(tǒng)計學(xué)差異。（4）三組治療后24h及7d血清NT-proBNP水平均較基線水平降低（P<0.01），，治療后7d較治療后24h進一步降低（P<0.01），左西孟旦組治療后7d血清NT-proBNP水平比其他兩組降低（P=0.006、0.003），有統(tǒng)計學(xué)差異。三組治療后7d血清ET-1和NE水平較基線水平降低（P<0.01），治療后7d左西孟旦組血清NE比其他兩組降低更多（P<0.017）。（5）隨訪三月，左西孟旦組再住院率明顯低于其他兩組（P=0.005、0.013），有統(tǒng)計學(xué)差異。（6）左西孟旦組比硝普鈉組不良反應(yīng)發(fā)生率低（P=0.01），與米力農(nóng)組比較無統(tǒng)計學(xué)差異（P=0.038）。結(jié)論：（1）左西孟旦能明顯改善AHF患者呼吸困難及全身臨床癥狀，縮小LVIDd，提高LVEF和FS，從而改善心臟收縮功能。（2）左西孟旦抑制AHF患者神經(jīng)內(nèi)分泌系統(tǒng)的激活，降低血清中NT-proBNP、ET-1和NE水平，阻斷心肌結(jié)構(gòu)重塑，對心臟起到保護作用，并且能夠降低近期再住院率，不良反應(yīng)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、米力農(nóng)和硝普鈉治療急性心力衰竭的對比研究

摘要5-8Abstract8-10縮略詞表11-12前言12-14對象與方法14-19結(jié)果19-23討論23-25結(jié)論25-26參考文獻26-28綜述28-35    參考文獻32-35作者簡介35-36致謝36

  本文關(guān)鍵詞：左西孟旦、米力農(nóng)和硝普鈉治療急性心力衰竭的對比研究，由筆耕文化傳播整理發(fā)布。