Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Aims The aim of the study was to evaluate the effects on systemicand coronary haemodynamics and myocar-dial substrate utilizationof a new calcium sensitizer, levosimendan, after coronary arterybypass grafting. Methods and Results Twenty-three low-risk patients were included in this randomizedand double-blind study. They received placebo (n=8), 8 (n=8)or 24 (n=7) µg.kg^–1of levosimendan after coronaryartery bypass operation. Systemic and coronary sinus haemodynamicswith thermodilution and myocardial substrate utilization weremeasured. The heart rate increased 11 beats.min^–1afterthe higher dose (P<0·05). Cardiac output increasedby 0·7 and 1·6l.min^–1(P<0·05 forboth) after 8 and 24µg.kg^–1of levosimendan, respectively.Systemic and pulmonary vascular resistance decreased significantlyafter both doses. Coronary sinus blood flow increased by 28and 42ml/(P=0·054 for the combined effect) after thelower and higher dose, respectively. Myocardial oxygen consumptionor substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increasemyocardial oxygen con-sumption or change myocardial substrateutilization. Thus levosimendan has the potential to treat lowcardiac output states after cardiopulmonary bypass surgery.     

Effect of the calcium sensitizer levosimendan on the performance of ischaemic myocardium in anaesthetised pigs

The calcium sensitizer levosimendan (LEV) improves the function of stunned myocardium, cardiac performance in heart failure, and possibly the efficiency of myocardial work. The present experiments investigated the effect of LEV on myocardial contraction and metabolism of acutely ischaemic myocardium distal to a functionally effective coronary artery stenosis. Anaesthetised open chest pigs (n = 14) were instrumented to assess heart rate (HR), aortic pressure (AoP), cardiac output (CO), blood flow in the left descending (QLAD) and circumflex (QLCX) coronary artery, myocardial end-diastolic segment length and systolic shortening (edL, MSS by sonomicrometry) in the LAD- and LCX-territory. Systemic vascular resistance (SVR), and a myocardial power index (PowI) for the LAD- and LCX-region were calculated. Following obstruction of QLAD by an external snare proximal to the first diagonal branch LEV was given intravenously (10 + 20 + 30 g/kg 15 min apart, n = 8) or the vehicle of LEV (n = 6). Following LEV haemodynamics and regional myocardial performance changed significantly: HR +22 min^–1, AoP –6 mmHg, CO +17%, SVR –21%; intact myocardium: QLCX +15%, RLCX –24%, PowILCX + 39%; ischaemic myocardium: QLAD –7%, MSSLAD –42%, PowILAD –27%. The data confirm the pharmacological profile of LEV: positive chronotropy, positive inotropy, and vasodilatation. The pump function of acutely ischaemic myocardium worsened following LEV. The efficiency of myocardial performance did not improve. A beneficial effect of LEV on the function of ischaemic myocardium was possibly outmanoeuvred by the increase in heart rate.     

Levosimendan Improves Renal Function in Patients with Acute Decompensated Heart Failure: Comparison with Dobutamine

Background Levosimendan is a relatively new cardiac inotropic agent with calcium sensitizing activity. This study was conducted to investigate the effects of levosimendan (L) and dobutamine (D) on renal function in patients hospitalized with decompensated heart failure (HF). Method The present study included 88 consecutive patients hospitalized with acutely decompensated HF (New York Heart Association (NYHA) Class 3–4) requiring inotropic therapy. Patients were randomized 2:1 to either L or D for intravenous inotropic support. Diuretic therapy was kept constant during infusions. Renal function values, including serum creatinine (CR), blood urea nitrogen, 24-h urinary output levels and calculated glomerular filtration rate (GFR) were measured just prior to and 24 h after the infusions in all patients, and 48 and 72 h after the infusions in every second patient in both groups. The pre and post-infusion values of renal function and left ventricular ejection fraction (LVEF) were evaluated. Results LVEF increased significantly in both groups. Those in L showed a significant improvement in calculated GFR after 24 h, whereas those in D showed no significant change (median in change in L:+15.3%, median change in D: −1.33%). Furthermore, in the L group a significant improvement was observed in calculated GFR after 72 h compared to baseline levels, whereas in D no significant change (median change in L:+45.45%, median change in D: +0.09%) was seen. Both agents improved 24-h urinary output. Conclusion Levosimendan seems to provide beneficial effects in terms of improvement in renal function compared to dobutamine in patients with heart failure who require inotropic therapy.     

An emerging role for calcium sensitisation in the treatment of heart failure

Heart failure occurs in 2 – 3% of the adult population in the developed world. With decompensation of cardiac function, haemodynamic stability can be achieved by using intravenous vasodilators, diuretics and inotropes. Unlike traditional inotropes, Ca2+ sensitisers enhance cardiac function without significantly increasing cardiac oxygen consumption, promoting arrhythmia or impairing lusitropy. The most promising drug in this new class is levosimendan, which has a unique dual mechanism; it enhances cardiac output through a Ca²⁺-dependent stabilisation of cardiac myofilaments and exhibits vasodilatory effects by opening ATP-dependent K⁺ channels. Clinical trials have demonstrated the beneficial haemodynamic effects of levosimendan, and prospective trials are currently underway to confirm its potential benefits on long-term prognosis. Updated guidelines from the European Society of Cardiology advise on how to incorporate levosimendan into care for patients who have acute heart failure.     

左西孟旦治疗失代偿心衰合并肾功能不全患者的疗效观察

目的 观察左西孟旦治疗失代偿心衰合并肾功能不全患者的疗效.方法 回顾性分析本科2013年7月至2015年5月住院治疗的63例失代偿心衰患者(男性41例,女性22例),患者按肾功能损害程度分为2组:肾功能重度损害组(L1组)33例[GFR:15 ～ ＜60 mL/(min·1.73 m2)]和肾功能轻度损害组(L2组)30例[GFR:60～ 89 mL/(min·1.73 m2)],输注左西孟旦治疗.比较、分析治疗后1、3、7、30 d患者N-末端脑钠肽前体(N-terminal pro-B-type natriuretic peptide,NT-pro-BNP)、左心室射血分数(left ventricular ejection fraction,LVEF)、肾小球滤过率(glomerular filtration rate,GFR)的变化.结果 2组间治疗前除GFR外,其余基线指标差异无统计学意义(P＞0.05);2组治疗后NT-pro-BNP 1、3、7d较基线显著下降(P＜0.05),LVEF 3、7d较基线显著上升(P＜0.05);2组间治疗前后NT-pro-BNP和LVEF差异无统计学意义(P＞0.05);2组治疗后GFR 1、3、7d较基线显著上升(P＜0.05),其中L1组GFR 30 d仍较基线显著上升(P＜0.05);L1组治疗后GFR改变量(△GFR)显著高于L2组(P＜0.05).结论 失代偿心衰合并肾功能不全患者应用左西孟旦,能够改善心肾功能,对肾功能显著下降患者的肾功能改善幅度更大、持续时间更长.     

左西孟旦对去甲肾上腺素诱导的心肌细胞钙瞬变信号的影响

目的:研究心肌细胞衰竭过程中钙瞬变信号的变化及左西孟旦(levosimendan,LeV)对其影响?方法:培养Sprague Dawley(SD)乳大鼠心肌细胞48 h后,分为对照组?去甲肾上腺素(NE)组?NE+LeV1(0.1 μmol/L)诱导组和NE+LeV2(1 μmol/L)诱导组?NE组以去甲肾上腺素10 μmmol/L诱导;NE+LeV1组先用NE诱导,再以LeV 0.1 μmol/L干预;NE+LeV2组先用NE诱导,再以LeV 1 μmol/L干预?用Ca2+荧光指示剂Fluo-3/AM负载心肌细胞,激光共聚焦显微镜观察心肌细胞钙瞬变信号变化以及心肌细胞的搏动频率?结果:① 与对照组相比,NE组心室肌细胞钙波分散?传导减慢?同步性较差,细胞搏动频率较快(26.7 ± 4.3 vs. 11.6 ± 3.6,P < 0.01)?收缩期钙瞬变峰值下降(128.37 ± 65.44 vs. 155.33 ± 61.77,P < 0.05)?达峰时间(Ttp,0.413 ± 0.324 vs. 0.212 ± 0.050,P < 0.01)?衰减时间(Tau,1.162 ± 0.524 vs. 0.722 ± 0.169,P < 0.01)均延长,钙瞬变幅度(60.80 ± 39.88 vs. 75.41 ± 36.52,P > 0.05)?谷值(67.57 ± 42.59 vs. 79.92 ± 38.05,P > 0.05)变化不大;② LeV处理后,钙波传导均匀同步,心肌细胞搏动频率及钙瞬变的峰值?幅度?谷值较NE组无明显变化,NE+LeV1组和NE+LeV2组Ttp分别为 (0.212 ± 0.044?0.205 ± 0.062)?Tau分别为(0.735 ± 0.269?0.753 ± 0.152)均较NE组缩短(P < 0.01);③NE+LeV1与 NE+LeV2两组相比,钙瞬变峰值和谷值?钙瞬变幅度?Ttp和Tau差别无统计学意义?结论:心肌细胞衰竭过程中钙瞬变减弱变慢?同步性较差;LeV通过增加钙瞬变速度?改善钙瞬变传导形式,发挥正性肌力作用?     

左西孟旦治疗顽固性心力衰竭合并肾功能不全的对照研究

目的 研究左西孟旦治疗顽固性心力衰竭合并肾功能不全的疗效.方法 将重庆市中山医院心内科67例顽固性心力衰竭合并重度肾功能不全患者分为左西孟旦治疗组(L组,n=33),多巴胺治疗组(D组,n=34).比较、分析治疗后1、3、7、30d患者N-末端脑钠肽前体(NT-pro-BNP)、左心室射血分数(LVEF)、肾小球滤过率(GFR)的变化.结果 治疗前,两组间基线指标差异无统计学意义(P＞0.05).L组:NT-pro-BNP治疗后1、3、7d较基线显著下降(P＜0.05),LVEF治疗后3、7d较基线显著上升(P＜0.05),GFR治疗后1、3、7、30 d与基线比较显著上升(P＜0.05).D组:NT-pro-BNP治疗后7d较基线显著下降 (P＜0.05),LVEF治疗后7d较基线显著上升(P＜0.05),GFR治疗后1、3、7、30 d较基线差异无统计学意义(P＞0.05).治疗后,NT-pro-BNp、LVEF、GFR的显著水平值L组均优于D组.结论 左西孟旦改善顽固性心力衰竭合并重度肾功能不全患者心、肾功能水平优于多巴胺.     

不同剂量左西孟旦治疗老年重症心力衰竭的临床研究

目的 分析不同剂量左西孟旦对老年重症心力衰竭患者心功能及预后的影响。方法 选取2016年5月—2019年6月金华市中心医院收治的老年重症心力衰竭患者150例。按照随机数字表法分为A、B、C组,每组50例。患者均给予常规治疗,伴有高血压、糖尿病等基础病患者给予降压、降糖药控制血压血糖,二尖瓣狭窄者需要进行球囊扩张、外科换瓣等治疗。在此基础上,A、B、C组分别给予剂量为0.2 μg/（kg·min）、0.3 μg/（kg·min）、0.4 μg/（kg·min）的左西孟旦治疗。比较3组心功能［左心室射血分数（LVEF）、每搏输出量（SV）、心肌做功指数（MPI）］、心衰标志物［氨基末端B型脑钠肽前体（NT-proBNP）］、心肌细胞［可溶性细胞凋亡因子（sFas）、sFas配体（sFasL）］、血流动力学［心率（HR）、平均动脉压（MAP）、心脏指数（CI）］、不良反应、1年存活率。结果 各组患者治疗前LVEF、SV、MPI比较,差异无统计学意义（P >0.05）。C组治疗后LVEF、SV较A组和B组增加（P <0.05）,MPI较A组和B组低（P <0.05）。各组患者治疗前NT-proBNP、sFas、sFasL水平比较,差异无统计学意义（P >0.05）。C组治疗后NT-proBNP、sFas、sFasL水平较A组和B组低（P <0.05）。各组患者治疗前MAP、CI、HR比较,差异无统计学意义（P >0.05）。C组治疗后MAP、CI较A组和B组高（P <0.05）,HR较A组和B组低（P <0.05）。各组患者不良反应率比较,差异无统计学意义（P >0.05）。各组患者1年生存率比较,差异无统计学意义（P >0.05）。结论 0.4 μg/（kg·min）剂量左西孟旦治疗老年重症心力衰竭患者疗效最佳,可有效改善心功能及血流动力学,降低心力衰竭严重程度,减少心肌细胞凋亡,预后较好,且未明显增加不良反应。