稳心颗粒联合尼可地尔治疗缺血性心肌病房性心律失常临床观察

目的探讨缺血性心肌病伴房性心律失常采用稳心颗粒联合尼可地尔治疗的临床效果。方法选择2017年1月—2019年1月收治的缺血性心肌病伴房性心律失常患者114例,遵照不同治疗原则分组标准分为对照组和研究组,各57例,2组入院后均采用常规基础治疗,对照组在基础治疗的基础上给予稳心颗粒进行治疗。研究组在对照组的基础上联合应用尼可地尔进行治疗,比较2组治疗效果、心功能情况、P波离散程度、6 min步行试验距离以及不良反应。结果研究组治疗总有效率为96.49%,显著高于对照组(80.70%),差异有显著性意义(P<0.05)。研究组心功能、P波离散程度、6 min步行距离以及脑钠素水平均显著好于对照组,差异均存在统计学意义(P<0.05),但2组患者用药后不良反应发生率比较,差异无统计学意义(P>0.05)。结论稳心颗粒联合尼可地尔应用于缺血性心肌病伴房性心律失常患者的治疗中,能够显著提高治疗效果,改善心脏功能,且未见明显不良反应,好于单一用药,值得推广。     

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis

Introduction: Nicorandil may exert cardioprotective effects in ischemic heart disease. However, its efficacy in combination with early reperfusion is uncertain. The authors performed a meta-analysis of the short- and long-term clinical outcomes of nicorandil administration at the time of primary percutaneous coronary intervention (PCI) in patients with ST-elevated myocardial infarction (STEMI).

Methods: PubMed, MEDLINE, Embase, and the Cochrane Library databases were systematically searched for eligible randomized controlled studies. The primary endpoint was major adverse cardiovascular events (MACE), both in-hospital and post-discharge. The secondary endpoint was the incidence of no-reflow phenomenon.

Results: Ten studies were included (n = 1105). Mean patient age was 63.0 ± 10.0 years; 76.6% of patients were male. Compared with controls who received primary PCI, combined nicorandil/primary PCI significantly reduced in-hospital MACE (pooled odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09–0.27), follow-up MACE (pooled OR 0.53; 95% CI 0.37–0.75), and total MACE (pooled OR 0.27; 95% CI 0.15–0.49). The combined treatment also reduced the incidence of no-reflow phenomenon (pooled OR 0.34; 95% CI 0.23–0.50).

Conclusion: Nicorandil administration at the time of primary PCI is associated with reduced MACE (both short- and long-term) and no-reflow phenomenon in patients with STEMI.     

芪白平肺胶囊对慢性阻塞性肺疾病痰瘀阻肺证大鼠血清CAM-2和VEGF的影响

目的 观察芪白平肺胶囊对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)痰瘀阻肺证大鼠血清钙调节蛋白-2(calmodulin-2,CAM-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响,探究其作用机制.方法 将280只SD大鼠随机分为正常组(60只)、模型组(60只)、芪白平肺胶囊预防组(芪预组,40只)、芪白平肺胶囊治疗组(芪治组,40只)、尼可地尔预防组(尼预组,40只)、尼可地尔治疗组(尼治组,40只).采用连续4周的强迫游泳、烟熏和低氧应激的复合方法复制COPD痰瘀阻肺证大鼠模型.正常组和模型组分别在实验第4周、第8周、第12周各处死20只大鼠,检测血清CAM-2和VEGF水平;芪预组和尼预组均在模型复制同时预防性给药4周,分别在实验第4周、第8周各处死20只大鼠,检测血清CAM-2和VEGF水平;芪治组和尼治组均在模型复制结束后连续给药4周,分别在实验第8周、第12周各处死20只大鼠,检测血清CAM-2和VEGF水平.结果 两因素方差分析结果显示,模型因素和时间因素对大鼠血清CAM-2和VEGF水平的主效应及其交互作用均具有统计学意义(P＜0.05).在实验第4周、第8周、第12周,模型组大鼠血清CAM-2水平均显著低于正常组(P＜0.05),血清VEGF水平均显著高于正常组(P＜0.05).与同时间模型组比较,尼预组和芪预组大鼠血清CAM-2水平显著升高(P＜0.05),而血清VEGF水平显著降低(P＜0.05).与同时间尼预组比较,芪预组CAM-2水平显著升高(P＜0.05),VEGF水平显著降低(P＜0.05).与同一时间模型组比较,芪治组和尼治组大鼠血清CAM-2水平显著升高(P＜0.05),VEGF水平显著降低(P＜0.05);在实验第12周,芪治组大鼠血清VEGF水平显著低于尼治组(P＜0.05).结论 芪白平肺胶囊和尼可地尔预防性给药和治疗性给药均可调节COPD痰瘀阻肺证大鼠血清CAM-2和VEGF的异常,芪白平肺胶囊的远期效应优于尼可地尔.     

高效液相色谱法测定尼可地尔缓释片的含量

目的建立尼可地尔缓释片的含量测定方法。方法采用HPLC法,Agilent TC-C18(4.6mm×250mm,5μm)色谱柱,甲醇-水(48∶52)为流动相,流速1.0m L/min,检测波长254nm。结果尼可地尔的线性范围为3.008μ/m L-18.048μ/m L,线性关系良好(r=0.9998);平均加样回收率为98.37%(n=5),RSD=0.72%。结论该方法简便、结果准确,适用于制剂中尼可地尔的含量测定与质量控制。     

尼可地尔对老年糖尿病并STEMI患者直接PCI缺血再灌注的心肌保护效应

目的：探讨尼可地尔对老年糖尿病并急性ST段抬高心肌梗死（STEMI）患者直接经皮冠状动脉介入（PCI）缺血-再灌注损伤（IRI）的心肌保护效应。方法：选取老年糖尿病并STEMI患者124例，均符合直接PCI适应证，按照分层区组随机化原则分为对照组（62例）和尼可地尔组（62例）。对照组患者行常规PCI；尼可地尔组在对照组治疗的基础上，术前给予注射用尼可地尔以0.06 mg·kg^-1（限制3~4 mg/次）静注，术中2 mg冠状动脉内给药，并以4 mg·h^-1静脉泵注24 h，之后尼可地尔片5 mg/次，3次/d，口服6个月。于术前及术后监测两组患者：（1）心肌IRI指标：血清心肌肌钙蛋白I（cTnI）及超敏肌钙蛋白T（hs-cTnT）；心力衰竭指标：N末端脑钠肽前体（NT-pro BNP）；（2）冠状动脉微循环灌注指标：心肌梗死溶栓试验（TIMI）血流分级和校正的TIMI帧数（CTFC）；（3）再灌注心律失常（RA）；（4）超声心动图检查左心室室壁运动评分指数（WMSI）和左室射血分数（LVEF）；（5）术后6个月内主要不良心血管事件（MACE）；（6）术后6个月内药物不良反应。结果：（1）于PCI术后0，6，12，24 h及术后3，7 d，尼可地尔组的血清cTnI水平均明显低于对照组（F_组间=62.537，P_组间<0.01）；（2）PCI术后尼可地尔组TIMI血流分级优于对照组（Z=-2.227，P=0.026），CTFC低于对照组（t=5.937，P<0.001）；（3）PCI后14 d尼可地尔组的WMSI低于对照组（t=14.974，P<0.001），LVEF高于对照组（t=-5.268，P<0.001）；（4）于术后1，3，7，14 d，尼可地尔组的血清NT-proBNP水平均低于对照组（F_组间=54.818，P_组间<0.01）；（5）IRA开通后4 h内尼可地尔组RA的发生率低于对照组（χ²=9.325，P=0.002）；（6）术后6个月内尼可地尔组MACE发生率低于对照组（χ²=4.613，P=0.032）；（7）两组患者药物不良反应发生率比较（χ²=0.614，P=0.433），差异无统计学意义。结论：尼可地尔对老年糖尿病并STEMI患者直接PCI的IRI具有心肌保护效应，能有效改善PCI后的心脏血流灌注，减轻心肌的IRI，改善室壁运动及左心功能，减少RA的发生，降低短期MACE发生率，且安全性好。     

尼可地尔对缺血性心力衰竭大鼠心功能的保护作用及机制

目的探讨尼可地尔对缺血性心力衰竭大鼠心功能和左室重构的保护作用及相关机制。方法将40只大鼠随机分为空白对照组(Con组)、尼可地尔组(NIC组)、生理盐水组(NS组)及假手术组(Sham组),每组10只,分别采取不同处理方式。记录各组大鼠体重、呼吸模式、活动量和毛色差异。术后8周所有大鼠行超声心动图检查。实验结束后对大鼠左心室前壁组织进行HE染色及电镜观察。检测心肌组织中p-Akt、Bcl-2、Bax蛋白的相对表达量。结果与Con组及Sham组相比,NS组及NIC组左心室射血分数(LVEF)、速度最大值(E)/心房收缩心室充盈速度最大值(A)(E/A)降低,NS组LVEF下降最多,差异有统计学意义(P<0.05)。左心室舒张末期容积(LVEDV)则呈相反趋势,3组间存在差异,NS组LVEDV最高,差异有统计学意义(P<0.05)。NS组左心室收缩末期容积(LVESV)、左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs)高于NIC组和Sham组,差异有统计学意义(P<0.05)。Sham组大鼠心肌细胞排列规则,横纹清晰;NS组心肌细胞排列紊乱,形状不规则,同时还表现出明显的纤维组织增生。Sham组、NIC组的左心室/体重比值(LVW/BW)和肺脏重量指数(Lungw/Bw)均低于NS组,差异有统计学意义(P<0.05)。与Con组及Sham组相比,NS组p-Akt、Bcl-2及Bax蛋白相对表达量增加,差异有统计学意义(P<0.05)。NIC组p-Akt、Bcl-2蛋白相对表达量高于NS组,但Bax蛋白表达量下降,差异均有统计学意义(P<0.05)。结论尼可地尔可通过改善心功能和左室重塑对缺血性心力衰竭大鼠起到保护作用,这可能与抑制Bax蛋白表达有关。     

The role of nicorandil in the treatment of myocardial ischaemia

Nicorandil is an anti-anginal agent that has been used in the United Kingdom for over 6 years and is becoming increasingly popular. It induces coronary and peripheral vasodilatation via a dualistic mode of action, mediated by the opening of potassium-ATP channels (K_ATP) and its nitrate effect by stimulation of adenyl cyclase, with an increase in cGMP levels. Comparison to nitrates and other anti-anginal agents have shown it to be of equal efficacy in relieving ischaemic symptoms. Recent evidence suggests a role for nicorandil as a myocardial preconditioning agent but this may be limited by systemic vasodilatation. There is ongoing research into its role in improving the long-term outcome of patients with ischaemic heart disease (IHD). It has been shown to be of proven efficacy in the treatment of IHD and further research will clarify other uses of this agent.     

Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs

Summary Nicorandil possesses hybrid properties as a nitrate and a potassium (K) channel opener. We have previously reported that large coronary arteries responded to nicorandil at low plasma concentrations, while dilatation of small coronary arteries only occurred at higher plasma concentrations (above 200 ng/ml) in chronically instrumented dogs. In this study we examined the effects of intravenous nicroandil on epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) in the absence and presence of glibenclamide, a K⁺ channel blocker, as well as the effects of nitroglycerin and cromakalim as reference drugs. The increase in CBF induced by nicorandil and cromakalim was significantly suppressed by glibenclamide. However, the increase in CoD induced by nicorandil and nitroglycerin was not suppressed by glibenclamide. These findings suggest that nicorandil-induced dilatation of the large coronary arteries was related to its nitrate action, while nicorandil-induced dilatation of the small coronary arteries was closely related to its effect as a K⁺ channel opener. In addition, the former response to nicorandil occurred at low concentrations, while the latter occurred at higher concentrations.     

Intractable hyperkalemia due to nicorandil induced potassium channel syndrome

Nicorandil is a commonly used antianginal agent, which has both nitrate-like and ATP-sensitive potassium (K_ATP) channel activator properties. Activation of potassium channels by nicorandil causes expulsion of potassium ions into the extracellular space leading to membrane hyperpolarization, closure of voltage-gated calcium channels and finally vasodilatation. However, on the other hand, being an activator of K_ATP channel, it can expel K⁺ ions out of the cells and can cause hyperkalemia. Here, we report a case of nicorandil induced hyperkalemia unresponsive to medical treatment in a patient with diabetic nephropathy.