西地那非联合贝前列素或阿托伐他汀治疗肺动脉高压的临床观察

目的比较西地那非联合阿托伐他汀、西地那非联合贝前列素治疗肺动脉高压的疗效及安全性。方法选择54例肺动脉高压患者随机分成2组,分别给予西地那非联合阿托伐他汀(A组)、西地那非联合贝前列素(B组)治疗,治疗前及治疗后6个月观察6 min步行距离(6MWD)、平均肺动脉压(mPAP)、肺血管阻力(PVR)和心脏指数(CI)。结果 2组均能增加6MWD,降低mPAP和PVR,提高CI,且西地那非联合贝前列素疗效更显著。2组间不良反应无明显差异,均未见严重不良反应。结论西地那非联合贝前列素治疗肺动脉高压的疗效优于西地那非联合阿托伐他汀,是一种安全有效的治疗方法。     

西地那非和前列地尔对风湿性心脏病肺动脉高压患者术中血流动力学的影响

目的观察西地那非和前列地尔对风湿性心脏病肺动脉高压患者术中血流动力学的影响。方法风湿性心脏病肺动脉高压患者45例,随机分为西地那非组(A组)、前列地尔组(B组)和对照组(C组),每组15例。A组鼻饲西地那非100mg;B组静脉泵入前列地尔20ng.kg-1.min-1;C组用等量生理盐水。记录围手术期血流动力学指标以及术后呼吸机辅助时间和需吸入氧浓度。结果与C组比较,A组、B组能显著降低平均肺动脉压(MPAP)、肺动脉血管阻力指数(PVRI)(P<0.05);与B组比较,A组能显著降低体循环血管阻力指数(SVRI)(P<0.05);A组术后呼吸机辅助时间及吸入氧浓度均低于B组(P<0.05)。结论西地那非的改善风湿性心脏病肺动脉高压患者术中血流动力学及心肺保护作用优于前列地尔。     

西地那非联合贝前列素钠治疗肺动脉高压患者疗效分析

目的 研究肺动脉高压患者应用西地那非联合贝前列素钠治疗的临床效果.方法 选取肺动脉高压患者60例,采用随机数字表法分为观察组和对照组,每组30例;对照组采取西地那非治疗,观察组采取西地那非联合贝前列素钠治疗,观察对比2组患者的不良发应发生率、动脉血气分析及生化指标、世界卫生组织心功能分级(WHO-FC分级)以及6 min步行步数.结果 观察组的不良反应发生率与对照组比较差异无统计学意义(P>0.05);观察组的动脉血气分析及生化指标优于对照组(P<0.05);观察组的WHO-FC分级以及6 min步行步数均优于对照组(P<0.05).结论 肺动脉高压患者应用贝前列素钠和西地那非治疗具有良好的临床效果,患者的心功能得到明显改善,活动耐力得到提高,且价格相对于其他药物更容易使患者接受,减少患者经济负担,因此值得在临床上进一步推广应用.     

波生坦联合西地那非治疗先天性心脏病合并肺动脉高压患儿的临床疗效及安全性评价

目的：探讨波生坦联合西地那非治疗先天性心脏病合并肺动脉高压患儿的临床疗效及不良反应发生情况。方法：选择2015年1月到2016年1月某院收治的90例先天性心脏病合并肺动脉高压患儿,随机分为对照组和试验组,各45例。对照组患儿给予西地那非治疗,试验组患儿给予波生坦联合西地那非治疗,两组患儿均治疗3个月。评价并比较两组患儿的临床疗效。检测并比较两组患儿治疗前后WHO肺动脉高压功能分级。采用右心导管检测测量并比较两组患儿治疗前后平均肺动脉压（mPAP）和肺血管阻力（PVR）。观察并比较两组患儿治疗期间不良反应的发生情况。结果：治疗后,试验组患儿的总有效率为95.56%,明显高于对照组患儿的73.33%,差异具有统计学意义（χ²=8.46,P=0.003 6）。治疗前,两组WHO肺动脉高压功能分级比较差异无统计学意义（P>0.05）;治疗后,两组WHO肺动脉高压功能Ⅱ级患儿均明显多于治疗前,WHO肺动脉高压功能Ⅲ级、Ⅳ级患儿均明显少于治疗前,差异均具有统计学意义（P<0.05）,同时试验组WHO肺动脉高压功能Ⅱ级患儿均明显多于对照组,WHO肺动脉高压功能Ⅲ级、Ⅳ级患儿均明显少于对照组,差异均具有统计学意义（P<0.05）。治疗前,两组患儿的mPAP、PVR比较,差异均无统计学意义（P>0.05）;治疗后,两组患儿的mPAP、PVR均明显小于治疗前,并且试验组患儿的mPAP、PVR均明显小于对照组,差异均具有统计学意义（P<0.05）。治疗期间,两组患儿的不良反应发生率比较,差异无统计学意义（χ²=1.01,P=0.908）。结论：波生坦联合西地那非治疗先天性心脏病合并肺动脉高压患儿临床疗效显著,且安全性较好,值得在临床上推广应用。     

不同剂量西地那非术后治疗婴幼儿先天性心脏病合并肺动脉高压的临床研究

目的探讨不同剂量西地那非对婴幼儿先天性心脏病合并肺动脉高压的疗效及不良反应,以便能制定婴幼儿最佳用药方案,减少不良反应的发生。方法先天性心脏病择期手术患儿128例按西地那非剂量分为4组:0.3mg/kg组(A组)、0.6mg/kg组(B组)、1.2mg/kg组(C组),1.8mg/kg组(D组),连续记录4组给药前、给药后3、7和14d的体动脉压、肺动脉压、动脉血氧饱和度、氧合指数,同时观察用药后患儿是否有不良反应。术后1个月复查体循环血压、肺动脉压。结果①部分高剂量患儿出现轻微不良反应,调整剂量后自行消失。②肺动脉收缩压动脉、血氧饱和度和氧合指数的比较:组内比较:各组用药前与用药3d比较差异均有统计学意义。组间比较:a.用药3d各组比较:A与B组P>0.05;C与D组比较P>0.05;A与C比较P<0.05;A与D比较P<0.05;B与C比较P<0.05;B与D比较P<0.05;b.用药7、14d两两组间比较,均为P>0.05。③体动脉收缩压:各组的组内和组间比较均为P>0.05。④复查肺动脉压组间比较均为P>0.05。结论婴幼儿应用西地那非不良反应轻;不同剂量用药3d后,各组所有患儿的肺动脉高压均有明显改善;短期内高剂量比低剂量的西地那非的疗效明显,但长期应用的降压效果是一致的,婴幼儿给药从小剂量(0.3mg/kg)开始,给药间隔则经验性的延长。     

西地那非联合辛伐他汀治疗慢性阻塞性肺疾病合并肺动脉高压患者的效果分析

目的 探讨西地那非联合辛伐他汀治疗慢性阻塞性肺疾病合并肺动脉高压患者的临床效果分析.方法 将2016年1月至2017年1月治疗的92例慢性阻塞性肺疾病合并肺动脉高压患者随机分为2组,2组均给予低流量吸氧,平喘、化痰、解除痉挛以及强心、利尿、改善心功能等常规对症治疗,在此基础上,对照组给予西地那非治疗,观察组给予西地那非联合辛伐他汀治疗,比较2组患者的临床疗效、肺功能、血氧分压、血氧饱和度、肺动脉压力及右心功能、各项实验室指标.结果 观察组治疗有效率为95.65％,较对照组的76.09％显著提高,2组有明显差异(P<0.05);2组治疗前FEV1、FEV1/FVC、FVC、SpO2、PaCO2、PaO2无明显差异(P>0.05);观察组治疗后FEV1、FEV1/FVC、FVC、SpO2、PaCO2、PaO2明显优于对照组,2组差异有统计学意义(P<0.05);两组治疗前PASP、mPAP、PVR、RVESD、RVEF、6MWD无显著差异(P>0.05);观察组治疗后PASP、PVR、RVESD、RVEF、6 MWD明显较对照组提高,2组差异有统计学意义(P<0.05);2组患者治疗前血浆NO、eNOS、hs-CRP、TNF-α、IL-1、IL-6、ET-1无明显差异(P>0.05);观察组治疗后血浆NO、eNOS、hs-CRP、TNF-α、IL-1、IL-6、ET-1较对照组明显改善,两组有统计学差异(P<0.05).结论 西地那非联合辛伐他汀治疗慢性阻塞性肺疾病合并肺动脉高压有确切疗效,能够改善肺功能及右心功能,有效扩张血管,降低肺动脉高压,减少全身炎症反应,具有积极的临床意义.     

贝前列素联合波生坦对中重度肺动脉高压的疗效观察

目的 观察贝前列素联合波生坦对中重度肺动脉高压（PH）的疗效.方法 30例中重度PH患者采用常规治疗及波生坦治疗,观察组在此基础上加用贝前列素钠,观察用药前后患者肺动脉收缩压（SPAP）、肺动脉平均压（mPAP）及肺动脉舒张压（DPAP）并进行统计学比较.结果 贝前列素与波生坦联用可较单独应用波生坦更有效地改善肺动脉压,两药联合治疗组SPAP和mPAP均显著降低,且两种治疗方案的不良反应发生率低.结论 贝前列素与波生坦联合治疗可能是PH安全有效的治疗方案.     

先天性心脏病合并肺动脉高压患儿57例临床分析

目的分析先天性心脏病合并肺动脉高压患儿的临床资料,以提高对该病的临床诊治水平。方法 57例患儿均予以吸氧、抗感染以及强心、利尿、扩血管治疗。11例左向右分流型先天性心脏病以及5例复杂型先天性心脏病经内科治疗后肺部感染、心力衰竭难以控制,转我院心外科予以手术。术后8例患儿用前列地尔,6例患儿用西地那非降肺动脉压力。患儿于内科治疗前后、手术后药物治疗前后测肺动脉压力(PAP)、左室射血分数(LVEF)及血浆N端-脑钠肽前体(NT-proBNP)。结果 38例左向右分流型先天性心脏病患儿经内科治疗后PAP、血浆NT-proBNP水平均较治疗前下降(P<0.05),LVEF较治疗前升高(P<0.05)。11例左向右分流型先天性心脏病以及5例复杂型先天性心脏病患儿PAP、血浆NT-proBNP水平均高于前述38例患儿(P<0.05),LVEF低于前述38例患儿(P<0.05)。8例患儿术后予以前列地尔,6例予以西地那非治疗后,PAP、血浆NT-proBNP水平较用药前下降(P<0.05),LVEF较用药前升高(P<0.05)。结论先天性心脏病合并肺动脉高压需早治疗,可改善预后。前列地尔、西地那非在治疗肺动脉高压方面是有效的。     

贝前列素联合西地那非对COPD合并肺动脉高压的临床研究

目的 探究患有慢性阻塞性肺疾病(COPD)合并肺动脉高压的患者使用贝前列素与西地那非联合治疗方案的临床效果.方法 选取2014年6月至2015年12月收集住院的COPD合并肺动脉高压的患者80例,采用随机分组法分为对照组、贝前列素组、西地那非组、贝前列素与西地那非联合用药组,每组20例;对比分析4组患者接受治疗后1、3、6个月的治疗效果.结果 贝前列素组、西地那非组与联合治疗组患者经过治疗运动耐力显著提高,患者的血气分析、血液流变性指标、心肌酶指标、血浆脑钠素(BNP)、左心室射血分数(LVEF)、右心房压、左右心室大小、PAP、6 min步行距离、肺功能检查均有明显改善.结论 通过使用两种联合药物作用的疗效的评估,可以一定程度降低COPD合并肺动脉高压患者的发病次数,降低其病死率,提高生活质量,具有较好的社会经济效应.     

左西孟旦与西地那非联合用药方案治疗慢性心力衰竭并发肺动脉高压的临床分析

目的探析左西孟旦与西地那非联合用药方案治疗慢性心力衰竭并发肺动脉高压的临床效果及不良反应,为临床医师选择合理用药方案提供参考。方法80例慢性心力衰竭并发肺动脉高压患者,依据随机数字表法分为A组和B组,每组40例。两组均进行基础治疗,A组增加左西孟旦与西地那非联合用药方案治疗。比较两组患者治疗前后左心室射血分数、N末端脑钠肽前体(NT-proBNP)、肺动脉收缩压水平,治疗前后血管内皮功能指标,临床治疗效果,不良反应发生情况。结果治疗后,A组左心室射血分数(51.21±7.09)%高于B组的(41.18±5.56)%,而NT-proBNP(3641.27±18.38)pg/ml、肺动脉收缩压(38.88±1.77)mm Hg(1 mm Hg=0.133 kPa)均低于B组的(4355.18±19.08)pg/ml、(43.28±2.08)mm Hg,差异具有统计学意义(P<0.05)。治疗后,A组血管内皮素-1、一氧化氮、内皮生长因子水平均优于B组,差异具有统计学意义(P<0.05)。A组临床治疗总有效率97.5%高于B组的80.0%,差异具有统计学意义(P<0.05)。两组未出现不良反应,比较差异无统计学意义(P>0.05)。结论左西孟旦与西地那非联合用药方案治疗慢性心力衰竭并发肺动脉高压,既能改善心功能,又能降低肺动脉收缩压、提高治疗效果,值得推荐。     

Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension

Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 microg) on day 1 and beraprost (40 microg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.     

Effects of Combined Treatment with Sildenafil and Itraconazole on the Cardiovascular System in Telemetered Conscious Dogs

Sildenafil, a potent PDE5 inhibitor, is widely prescribed as a treatment of erectile dysfunction. Itraconazole is an inhibitor of CYP3A4, a metabolic enzyme of sildenafil. In the current study, we investigated the effects of single treatment with sildenafil and combined treatment with sildenafil and itraconazole on blood pressure, heart rate, and QT interval in conscious beagle dogs. After a transmitter was implanted to beagle dogs for conscious state experiments, a single oral dose of sildenafil was administered to the beagle dogs at dose levels of 3, 15, and 30 mg/kg. Blood pressure, heart rate, and lead II ECG were measured prior to dosing and at 0.5, 1, 2, 4, 6, and 24 h postdosing. In the study of combined treatment with sildenafil and itraconazole, the 100 mg/kg dose of itraconazole was orally administered 1 h prior to oral administration of sildenafil. No changes in blood pressure were observed at any doses in animals receiving either single treatment with sildenafil or combined treatment with sildenafil and itraconazole. Increased heart rate from 0.5 h to 6 h postdosing and decreased QT interval were observed in animals receiving single treatment with sildenafil at 15 or 30 mg/kg. When 30 mg/kg of sildenafil was coadministered with 100 mg/kg of itraconazole, drug-related effects such as increased heart rate and decreased QT interval were significantlyenhanced as compared to sildenafil-alone administration at 6 h postadministration. These results demonstrated that increased heart rate and decreased QT interval, the adverse effects of sildenafil, were enhanced and prolonged when sildenafil was coadministered with itraconazole. Therefore, caution should be taken when sildenafil is coadministered with itraconazole, a CYP3A4 inhibitor, or when administered to elderly patients or patients with hepatic or renal impairment who cannot metabolize and excrete sildenafil normally.     

Effects of combined treatment with sildenafil and itraconazole on the cardiovascular system in telemetered conscious dogs

Sildenafil, a potent PDE5 inhibitor, is widely prescribed as a treatment of erectile dysfunction. Itraconazole is an inhibitor of CYP3A4, a metabolic enzyme of sildenafil. In the current study, we investigated the effects of single treatment with sildenafil and combined treatment with sildenafil and itraconazole on blood pressure, heart rate, and QT interval in conscious beagle dogs. After a transmitter was implanted to beagle dogs for conscious state experiments, a single oral dose of sildenafil was administered to the beagle dogs at dose levels of 3, 15, and 30 mg/kg. Blood pressure, heart rate, and lead II ECG were measured prior to dosing and at 0.5, 1, 2, 4, 6, and 24 h postdosing. In the study of combined treatment with sildenafil and itraconazole, the 100 mg/kg dose of itraconazole was orally administered 1 h prior to oral administration of sildenafil. No changes in blood pressure were observed at any doses in animals receiving either single treatment with sildenafil or combined treatment with sildenafil and itraconazole. Increased heart rate from 0.5 h to 6 h postdosing and decreased QT interval were observed in animals receiving single treatment with sildenafil at 15 or 30 mg/kg. When 30 mg/kg of sildenafil was coadministered with 100 mg/kg of itraconazole, drug-related effects such as increased heart rate and decreased QT interval were significantly enhanced as compared to sildenafil-alone administration at 6 h postadministration. These results demonstrated that increased heart rate and decreased QT interval, the adverse effects of sildenafil, were enhanced and prolonged when sildenafil was coadministered with itraconazole. Therefore, caution should be taken when sildenafil is coadministered with itraconazole, a CYP3A4 inhibitor, or when administered to elderly patients or patients with hepatic or renal impairment who cannot metabolize and excrete sildenafil normally.     

贝前列素钠对脑缺血再灌注损伤大鼠血清IL-6、TNF-α水平及MPO活性影响

目的:探讨贝前列素钠对脑缺血再灌注大鼠血清白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)及髓过氧化物酶(MPO)的影响。方法:将雄性SD大鼠随机分为假手术组、模型组、贝前列素钠低剂量组、贝前列素钠中剂量组、贝前列素钠高剂量组。采用Zea Longa线栓方法造成大鼠局灶性脑缺血再灌注模型。术前30 min各组灌胃给药,贝前列素钠低、中、高剂量组分别给予贝前列素钠15,30,60 μg·kg^-1·d^-1灌胃,对照组和模型组给予10 ml·kg^-1·d^-1的生理盐水。术后24 h处死大鼠制备血清,ELISA法检测各组血清IL-6、TNF-α水平及MPO活性。结果:贝前列素钠低、中、高剂量组大鼠血清IL-6 、TNF-α水平及MPO活性明显低于模型组(P<0.05)。结论:贝前列素钠能够抑制大鼠脑缺血再灌注损伤时炎症细胞因子的表达,降低脑缺血再灌注损伤的程度。     

Investigation on interaction between tacrolimus and sildenafil in kidney-transplanted patients with erectile dysfunction

OBJECTIVE: Sildenafil may provide an effective treatment for erectile dysfunction, frequently observed in uremic patients and after kidney transplantation. Pharmacokinetic interactions between sildenafil and tacrolimus are to be expected due to a common elimination pathway via cytochrome P450 3A4. Therefore, the pharmacokinetics during combined use of these agents were studied over 9 days. MATERIAL AND METHODS: Nine male patients (age 29-52 years) were included, who had previously participated in a recent interaction study with sildenafil given as a single dose. Comedication remained unchanged in order to avoid introducing confounding factors. In the previous study in the patients, tacrolimus blood levels with and without sildenafil were measured for pharmacokinetic analysis. In the present study, 25 mg sildenafil were coadministered daily over 9 days and tacrolimus levels were assessed at sampling times optimized using simulation. In addition, laboratory parameters and blood pressure changes were measured and adverse effects monitored. RESULTS: Terminal half-lives of tacrolimus did not differ significantly and trough levels did not change when sildenafil was coadministered daily over 9 days. Mean arterial blood pressure was lower after sildenafil intake. Two patients had to reduce their antihypertensive treatment, 6 patients reported mild side effects. In 1 case, there was an asymptomatic, temporary increase in the serum concentration of gamma-GT. CONCLUSIONS: There was no evidence obtained for a change in elimination half-life or average concentration of tacrolimus during repeated coadministration of sildenafil. Since blood pressure decreased, a starting dose of 25 mg sildenafil and, if necessary, adjustment of the dose of antihypertensive drugs on days when sildenafil is given has to be considered. With respect to the observed blood pressure changes, pharmacokinetic/pharmacodynamic interaction studies with other antihypertensive drugs are of critical importance in these patients.     

氨氯地平联合贝前列素钠治疗高血压早期肾损害临床研究

目的探讨氨氯地平联合贝前列素钠治疗高血压早期肾损害的疗效,以及对患者β2微球蛋白(β2-MG)、胱抑素C(CysC)、同型半胱氨酸(HCY)和尿微量白蛋白(m ALB)的影响。方法选取医院2017年5月至2018年5月接诊的高血压合并早期肾损害患者98例,按治疗方式不同分为治疗组和对照组,各49例。两组患者均给予常规基础治疗及苯磺酸氨氯地平片治疗,在此基础上,治疗组患者给予贝前列素钠片治疗。两组患者均治疗2个月。结果治疗后,两组患者的收缩压(DBP)和舒张压(SBP)均下降,且治疗组明显低于对照组(P <0. 05);两组患者的β2-MG,CysC,m ALB,HCY均下降,且治疗组显著低于对照组(P <0. 05);两组患者的白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)和超敏C反应蛋白(hs-CRP)水平均下降,且治疗组显著低于对照组(P <0. 05);治疗组不良反应发生率为6. 12%,与对照组的12. 24%相当(P> 0. 05)。结论氨氯地平联合贝前列素钠对高血压合并早期肾损害患者的肾脏保护作用更显著,其机制可能与稳定血压和抑制炎性反应有关,且安全性较高。     

西地那非联合高频振荡通气治疗足月新生儿肺动脉高压的效果观察

目的 观察西地那非联合高频振荡通气(HFOV)治疗足月新生儿肺动脉高压(PPHN)的临床效果.方法 回顾性分析2008年1月至2014年12月本院新生儿重症监护病房收治的PPHN患儿临床资料,根据不同时间段治疗措施不同分为HFOV组、常频机械通气(CMV)+西地那非组、HFOV+西地那非组.分析各组患儿治疗前、治疗3、6、12 h后的P/F比值、氧合指数(OI)、肺动脉压力,以及机械通气时间、氧疗时间、住院时间、转归.结果 治疗3、6、12 h后HFOV+西地那非组P/F、OI、肺动脉压力均优于CMV+西地那非组和HFOV组,CMV+西地那非组优于HFOV组,差异有统计学意义(P＜0.05).HFOV+西地那非组机械通气时间、氧疗时间、住院时间均短于CMV+西地那非组和HFOV组,CMV+西地那非组短于HFOV组,差异有统计学意义(P＜0.05);各组患儿病死率比较差异无统计学意义(P＞0.05).结论 早期西地那非联合HFOV治疗PPHN疗效显著,能迅速改善肺动脉高压患儿的氧合情况,显著缩短患儿的上机时间、氧疗时间及住院时间,但对患儿病死率没有影响.     

辛伐他汀联合西地那非治疗慢性阻塞性肺疾病合并肺动脉高压的临床研究

目的探讨辛伐他汀联合西地那非治疗慢性阻塞性肺疾病（COPD）合并肺动脉高压（HP）的临床效果。方法选取本院80例COPD合并HP患者,将其随机分为治疗组（40例）和对照组（40例）;对照组给予常规治疗加用辛伐他汀,治疗组在对照组基础上加用西地那非治疗;观察比较两组治疗前后肺动脉平均压变化、6min步行距离、PaO2、PaCO2的情况及不良反应。结果治疗后,两组患者肺动脉平均压及6min步行距离与治疗前比较,差异有统计学意义（P〈0.05）;治疗组治疗后肺动脉平均压变化及6min步行距离与对照组比较,差异有统计学意义（P〈0.05）。治疗后两组患者的PaO2、PaCO2与治疗前比较,差异有统计学意义（P〈0.05）;治疗组治疗后PaO2、PaCO2与对照组比较,差异有统计学意义（P〈0.05）。结论辛伐他汀联合西地那非治疗COPD合并HP疗效显著,值得临床推广应用。