Hemodynamic effects of sildenafil in patients with stable ischemic heart disease

Background: Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. The hemodynamic effects of sildenafil may be potentially hazardous for patients with cardiac disease. Sildenafil has been reported to augment the hypotensive effects of nitrates. There is sparse information regarding the systemic and pulmonary hemodynamic effects of a single oral dose of sildenafil in patients with stable angina. Methods: Male patients referred for coronary angiography with diagnosis of chronic stable angina were enrolled in this study to assess the acute hemodynamic effects of sildenafil. Patients receiving long-acting or sublingual nitrates for the last 6 h before the study were excluded. Hemodynamic measurement were taken during right and left heart catheterization in the basal state and 60 min after 50 mg of oral sildenafil. Results: Twelve patients (age 53±7 years) were studied. All had stable angina CCS class II or III. Four had previous myocardial infarction. By coronary angiography, seven patients had at least one coronary artery with >70% stenosis, four had at least one with 50–70% stenosis, and one had only intimal irregularities. There were no significant effects of sildenafil on systemic or pulmonary arterial pressure, left ventricle endiastolic pressure, cardiac output, and systemic or pulmonary vascular resistance (P>0.05 for all). No adverse events were observed. Conclusion: A single oral dose of sildenafil had no significant hemodynamic effect in supine patients with stable angina. Isolated administration of sildenafil does not appear to be associated to adverse cardiovascular effects.     

PDE5抑制剂与cGMP信号通路相关疾病的研究进展

磷酸二酯酶5(phosphodiesterase 5,PDE5)抑制剂通过阻断环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)的分解,使包括一氧化氮(nitric oxide,NO)在内的血管舒张介质作用延长,从而导致阴茎和肺的血管舒张。PDE5主要在阴茎海绵体和肺血管中发现,所以其抑制剂的主要作用是延长阴茎勃起和降低肺血管压力。     

Short term effects of sildenafil citrate therapy in secondary pulmonary hypertension

ObjectivesTo study the short term effects of sildenafil citrate therapy in patients with secondary pulmonary hypertension.MethodsForty patients with known symptomatic secondary pulmonary hypertension due to valvular heart disease, chronic thromboembolic disease, chronic obstructive pulmonary disease, interstitial pulmonary fibrosis, and idiopathic dilated cardiomyopathy were included in this phase II study. Patients were allocated in a randomized, placebo controlled design to either sildenafil or placebo for 6 weeks. Baseline and 6 week follow up included assessment of hemodynamic parameters, functional class using the NYHA classification, echocardiographic measurements of pulmonary artery systolic pressure and left ventricular ejection fraction.ResultsThe mean NYHA class at 6 weeks was 2.05 ± 0.4 in the sildenafil group versus 2.6 ± 0.6 in the placebo group, p = 0.02. The mean systolic pulmonary artery pressure significantly decreased in the sildenafil group at 6 weeks (43 ± 4 mmHg), compared to placebo patients (53 ± 7 mmHg), p = 0.02. Ejection fraction was higher in the sildenafil group, 59 ± 12% versus 54 ± 14% in the placebo group, but did not reach statistically significant difference. Sildenafil was well tolerated with minimal side effects.ConclusionOur data suggest that sildenafil therapy may provide benefits to selected patients with pulmonary hypertension secondary to cardiac or pulmonary diseases.     

Inhibitory effects of sildenafil and tadalafil on inflammation,oxidative stress and nitrosative stress in animal model of bronchial asthma

BackgroundCyclic neucleotides are involved in many cellular functions including smooth muscle relaxation, inflammation, and signal transduction. Sildenafil and tadalafil are phosphodiesterase-5 (PDE-5) inhibitors which prevent the degradation of cyclic neucleotide i.e. guanosine 3′,5′ cyclic monophosphate (cGMP) and increase the levels of cGMP. In this study sildenafil and tadalafil were evaluated for their anti-inflammatory, anti-oxidative and anti-nitrosative stress potential in animal model of bronchial asthma.MethodsWistar rats were sensitized with 10 mg intraperitoneal (ip) ovalbumin adsorbed to 10 μg of aluminum hydroxide on day 0. Animals were given sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip) from day 1 to day 14. Also, on day 14 animals were challenged with ovalbumin (1 mg ip). After 24 h, samples were collected to analyze interleukin-4 (IL-4) and tumour necrosis factor-α (TNF-α), in serum and bronchoalveolar lavage fluid (BALF). The oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide metabolites (NO_x) were also measured in serum.ResultsPre-treatment with sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip) significantly reduced the levels of pro-inflammatory cytokines IL-4 and TNF-α in rat serum and BALF. In addition, pre-treatment with both the drugs decreased the levels of MDA and NO_x and increased the levels of GSH in serum.ConclusionsSildenafil and tadalafil decreased pro-inflammatory cytokines in serum and BALF. Both drugs inhibit oxidative and nitrosative stress in animal model of bronchial asthma and could have a therapeutic potential in bronchial asthma.     

枸橼酸西地那非对宫腔粘连术后冻融胚胎移植妊娠结局的影响

目的：观察枸橼酸西地那非（万艾可）对宫腔粘连（intrauterine adhesion,IUA）分离术后冻融胚胎移植（frozen embryo transfer,FET）患者妊娠结局的影响。方法：选择2017年1-12月在南京医科大学附属妇产医院行FET的不孕症患者,在进入FET周期前宫腔镜检查确诊IUA,行宫腔镜下IUA分离术,术后复查宫腔镜显示宫腔形态正常行FET,共310例。根据患者是否添加枸橼酸西地那非将患者分为2组,其中A组（对照组）实施激素替代周期FET,共190例;B组（治疗组）为激素替代周期并在患者月经干净后每日阴道给予枸橼酸西地那非50 mg,应用至移植前,共120例。首先比较2组患者的妊娠结局,其次将A组及B组患者进一步分为轻度IUA组和中重度IUA组,比较2组之间的差异。结果：B组临床妊娠率［50.83%（61/120）］高于A组［34.74%（66/190）］,差异有统计学意义（P＜0.05）;B组胚胎种植率［31.17%（72/231）］略高于A组［21.82%（79/362）］,但差异无统计学意义（P＞0.05）。与A组相比,B组轻度IUA患者的临床妊娠率与胚胎种植率差异无统计学意义（P＞0.05）;B组中重度IUA患者的临床妊娠率［44.78%（30/67）］及胚胎种植率［28.46%（37/130）］均高于A组,差异有统计学意义（P＜0.05）。2组间流产率和异位妊娠率比较差异均无统计学意义（P＞0.05）。结论：应用枸橼酸西地那非可提高IUA术后患者子宫内膜容受性,尤其对中重度IUA术后患者可显著提高其FET妊娠率。     

近红外特征谱段相关系数法鉴别保健品中非法添加枸橼酸西地那非的研究

目的：快速准确鉴别保健品中是否非法添加枸橼酸西地那非。方法：用近红外特征谱段相关系数法快速鉴别保健品中非法添加枸橼酸西地那非。结果：近红外特征谱段相关系数法可以快速、准确鉴别保健品中非法添加枸橼酸西地那非,总体正确率达到94.4%。结论：该方法快速、简便、灵敏、结果准确,适用于现场监督检查时快速鉴别保健品中是否非法添加枸橼酸西地那非,值得在现场监督检查时推广应用。     

Prevention of Right Heart Failure After Left Ventricular Assist Device Implantation by Phosphodiesterase 5 Inhibitor

Right ventricular (RV) function immediately after left ventricular assist device (LVAD) implantation is a crucial prognostic factor. RV failure is linked to increased mortality and worse outcome. A phosphodiesterase 5 inhibitor, sildenafil, was shown to decrease pulmonary vascular resistance and pulmonary artery pressure post‐LVAD. We report on a series of heart failure patients, and the effect of sildenafil on the incidence of RV failure after LVAD implantation. We retrospectively analyzed the data of end‐stage heart failure patients who underwent LVAD implantation with pulmonary hypertension and RV dysfunction prior to surgery. Patients were divided into two groups; group 1: patients who received sildenafil perioperatively, and group 2: patients who did not receive sildenafil. Hemodynamic and echographic data were collected before and after surgery. Fourteen patients were included, 8 patients in group 1 and 6 in group 2. Sildenafil was administered with a mean dose of 56.2 ± 9.4 mg in group 1 and was able to significantly reduce right heart failure incidence, and to demonstrate a significant reduction in pulmonary vascular resistance, pulmonary artery pressure, transpulmonary gradient, and a significant increase in cardiac output. In conclusion, sildenafil seems to have a promising role perioperatively in preventing acute RV failure postsurgery in patients with RV dysfunction and pulmonary hypertension, requiring LVAD therapy.     

液相色谱-质谱联用同时测定西洋参制剂中人参皂苷Rg1、Re、Rb1及抗疲劳类非法添加含量

目的 建立同时测定西洋参制剂中人参皂苷Rg1、Re、Rb1及抗疲劳类非法添加含量的液相色谱-质谱联用方法.方法采用Agilent ZORBAX SB-C18色谱柱（3.0mm×150mm,3.5μm）,流动相A为含0.1%乙酸的20mmol·L-1乙酸铵溶液,流动相B为甲醇∶乙腈（3：2）的混合溶液,采用线性梯度洗脱;流速为200μL·min-1,柱温35℃.质谱条件采用电喷雾离子化（ESI）方式,正负离子模式,以多级反应监控（MRM）模式对西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1进行含量测定.结果 西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1分别在2.99～59.85,0.43～8.60,3.32～66.42,3.16～63.29,2.63～52.68,4.15～82.93μg·mL-1浓度范围内与峰面积呈良好线性关系.西洋参制剂中西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1的平均加样回收率均介于92.9%～103.3%之间.结论 本法简单、快速、灵敏、准确,可用于西洋参制剂中西地那非、伐地那非、他达拉非、人参皂苷Rg1、人参皂苷Re和Rb1含量测定,为该药的质量控制提供依据.     

一种西地那非类似物的合成工艺研究

目的 探讨合成一种西地那非类似物的新方法.方法 设计以WG 001-01-08和五硫化二磷为原料,经过硫化得到目标化合物（一种西地那非类似物）的合成路线,并以收率和杂质为指标考察反应试剂、反应温度、加料顺序对反应的影响.结果 成功制备了目标化合物,收率为90％;较佳反应条件为以4-甲基吡啶为溶剂,120℃反应4h,先加WG001-01-08后加五硫化二磷.结论 新方法收率较高,杂质少,反应条件温和,适合工业化生产.     

西地那非和酚妥拉明治疗勃起功能障碍的临床疗效比较

目的：比较西地那非和酚妥拉明治疗勃起功能障碍的临床效果和安全性。方法选取2011年6月—2014年6月南京市妇幼保健院收治的勃起功能障碍患者223例,随机分为对照组（n=108例）和治疗组（n=115例）。对照组性交前0.5～1 h口服甲磺酸酚妥拉明片,1片/次;治疗组在性交前0.5～1 h口服枸橼酸西地那非片。首次使用时推荐剂量为50 mg,根据后期个体疗效情况调节剂量,范围在25～100 mg。两组每日最多服用1次,每周至少1次但不超过4次,均连续治疗8周。比较两组的临床疗效,同时比较两组患者治疗前后勃起功能国际指数问卷表（IIEF-5）评分、勃起质量量表（EQS）评分、平均起效时间和性交持续时间。结果治疗后,治疗组和对照组的总有效率分别为86.9%、63.9%,两组总有效率比较差异有统计学意义（P＜0.05）。治疗后,两组IIEF-5评分和EQS评分均较治疗前显著增加,同组治疗前后差异有统计学意义（P＜0.05）,且治疗后,治疗组这两项评分均显著高于对照组,两组比较差异有统计学意义（P＜0.05）。治疗组平均起效时间和平均性交持续时间均显著长于对照组,两组比较差异有统计学意义（P＜0.05）。结论西地那非治疗勃起功能障碍有较好的临床疗效,疗效优于酚妥拉明,可进行临床推广使用。