Levosimendan suppresses oxidative injury,apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25?mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia (^§§§p?<?0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p?<?0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p?<?0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.     

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。     

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.     

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.