安立生坦在先天性心脏病术后肺动脉高压中的治疗效果

目的:评估安立生坦在先天性心脏病术后肺动脉高压中的治疗效果。方法:我们选取2013年2月~12月70例先天性心脏病术后肺动脉高压的患者。随机分为试药组(n=35)和对照组(n=35)。试药组给予安立生坦+常规治疗,对照组仅给予常规治疗。12周后患者门诊随访,评估心功能状况、行心脏彩超评估肺动脉压力,并化验检测肝肾功能指标。结果:试药组[(38±5)mm Hg vs.(50±6)mm Hg,P0.05]和对照组[(41±6)mm Hg vs.(47±7)mm Hg,P0.05]患者术后12周肺动脉压力较术后第3天均明显降低,尽管如此,试药组肺动脉压力降低幅度明显大于对照组[(12±4)mm Hg vs.(6±3)mm Hg,P0.05]。试药组患者中30例(86%)心功能明显改善,对照组中25例(71%)心功能明显改善,两者有显著差异(P0.05)。试药组患者未见肝功能损害及贫血病例。结论:先天性心脏病术后肺动脉高压的患者使用安立生坦能够安全有效地降低肺动脉压力,改善心功能。     

左卡尼汀联合伐地那非治疗肺动脉高压的临床疗效研究

目的观察左卡尼汀联合伐地那非治疗肺动脉高压(PAH)的临床疗效。方法选取2010年10月—2013年3月我院心内科住院及门诊确诊的PAH患者64例,将其随机分为治疗组和对照组,各32例。对照组采用常规治疗,治疗组在常规治疗的基础上加用左卡尼汀和伐地那非治疗,均治疗6个月。记录患者治疗前后6分钟步行距离(6MWD)、肺动脉收缩压(PASP)、WHO肺动脉高压患者功能分级(WHO-PHA功能分级)、心率及血压变化,观察药物的安全性和耐受性。结果治疗前两组患者6MWD、PASP及WHO-PHA功能分级比较,差异均无统计学意义(P0.05);治疗后治疗组6MWD大于对照组,PASP低于对照组,WHO-PHA功能分级优于对照组(P0.05)。两组患者治疗前后心率、收缩压和舒张压比较,差异均无统计学意义(P0.05)。结论左卡尼汀联合伐地那非治疗PAH,可以提高患者活动耐量、降低PASP、改善WHO-PHA功能分级,且安全性、耐受性良好。     

5型磷酸二酯酶抑制剂改善特发性肺动脉高压患者预后

目的:探讨5型磷酸二酯酶(PDE5)抑制剂对特发性肺动脉高压(IPAH)患者预后的影响.方法:纳入2005-05至2009-08期间在我院本部肺血管病诊治中心住院并新诊断为IPAH的患者89例.根据患者是否接受PDE5抑制剂分为PDE5抑制剂组(52例)及对照组(37例).通过回顾性查阅病历收集患者的基线资料,申话随访和(或)查阅患者门诊病历获取患者生存状态及治疗情况.结果:PDE5抑制剂组及对照组在年龄、性别、身高、体重、血压、心率、世界卫生组织(WHO)肺动脉高压功能分级、6分钟步行距离、血流动力学及接受基础治疗比例,差异均无统计学意义(P均>0.05).对89例患者平均随访(20.12±14.69)月,随访期间26例患者死亡.PDFA抑制剂组1、2、3年生存率明显高于对照组,差异有统计学意义(P<0.05).WHO肺动脉高压功能分级为III/IV级的患者,PDE5抑制剂组1、2、3年生存率明显高于对照组,差异有统计学意义(P<0.05);WHO肺动脉高压功能分级为I/Ⅱ级的患者,PDE5抑制剂组1、2、3年生存率较对照组有改善的趋势,但差异无统计学意义(P>0.05).当未包括6分钟步行距离时,84例患者多因素COX分析结果显示:体重(风险比=0.944,P=0.047),混合静脉血氧饱和度(风险比=0.934,P=0.006),接受PDE5抑制剂治疗(风险比=0.314,P=0.006)三参数将有助于评估IPAH患者的预后.当纳入6分钟步行距离时(n=41),多因素COX分析显示年龄(风险比=0.860,P=0.004)、6分钟步行距离(风险比=0.984,P=0.001)及接受PDE5抑制剂治疗(风险比=0.072,P=0.001)三参数将有助于评估IPAH患者的预后.结论:PDE5抑制剂对改善IPAH患者的预后有益.     

西地那非治疗肺动脉高压疗效和安全性的初步观察

目的 探讨西地那非治疗对肺动脉高压患者的临床疗效及耐受性,为西地那非治疗肺动脉高压提供依据.方法 连续入选2007年5月至2009年4月阜外心血管病医院收治的肺动脉高压患者56例,其中男11例,女45例,年龄(31±11)岁.给予西地那非25 mg口服,3次/d,记录治疗前和治疗12周后患者心功能和肺动脉高压功能分级、6 min步行距离、Borg呼吸困难指数、血流动力学改变及临床症状,同时监测患者血液循环及实验室检测指标及不良反应.结果 治疗12周后,患者心功能和肺动脉高压功能分级有明显改善(P<0.01),其中2例Ⅳ级升高至Ⅲ级;8例Ⅲ级改善为Ⅱ级,2例升高至Ⅰ级;5例Ⅱ级升高至Ⅰ级.无纽约心功能分级及世界卫生组织肺动脉高压功能分级恶化病例;6 min步行距离由(352±80)m增加至(396±78)m;差值为(44±70)m(P<0.01);肺动脉平均压降低(6±14)mm Hg(1 mm Hg=0.133 kPa)、肺血管阻力降低(490±832) Dys·s·cm-5(均P<0.01)心输出量增加(1.1±2.0) L/min,P<0.01;心指数增加(0.7±1.1) L·min-1·m-2(均P<0.01).患者无临床恶化情况,耐受性良好,无严重不良事件.结论 西地那非治疗可显著改善肺动脉高压患者功能分级,活动耐力及血流动力学.

Abstract：

Objective To explore the safety and efficacy of oral sildenafil therapy for pulmonary arterial hypertension(PAH), and to provide evidence for sildenafil treatment for Chinese patients with PAH. Methods In this 12-week, prospective, open-label, uncontrolled study, 56 patients with PAH were given oral sildenafil (25 mg, tid). The primary end point was change from baseline to 12 weeks in exercise capacity assessed by 6 min walk (6MW) test. Secondary end points included changes in WHO class and cardiopulmonary hemodynamics. Clinical worsening was defined as death, transplantation, hospitalization for PAH, or initiation of additional therapies for PAH, such as intravenous epoprostenol or oral bosentan. Results After 12 weeks, the compliance was good in 56 patients. Significant improvement was seen in NYHA heart function class and WHO class as compared to baseline(P<0.01): from class Ⅳ to class Ⅲ in 2, from class Ⅲ to class Ⅱ in 8 and to class Ⅰ in 2 cases, and from class Ⅱ to class Ⅰ in 5 cases. No NYHA heart function class and WHO PAH function class deterioration were observed. Oral sidenafil increased 6MW distance, from (352±80) m to (396±78) m, with a change of (44±70) m(P<0.01). Significant improvement was seen in hemodynamics (mean pulmonary artery pressure, P<0.01; cardiac index, P<0.01; pulmonary vascular resistance, P<0.01) at week 12 as compared with baseline. Mean right atrial pressure decreased (3±11)mm Hg (1 mm Hg=0.133 kPa), mean pulmonary arterial pressure decreased (6±14) mm Hg, cardiac output increased (1.1±2.0)L/min, cardiac index increased (0.7±1.1)L·min-1·m-2, and total pulmonary resistance decreased (490±831) Dys·s·cm-5. Side effects were mild and consistent with those reported with sildenafil treatment. No statistically significant clinical worsening was observed with sildenafil therapy for PAH patients. Conclusions Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with pulmonary arterial hypertension.     

中老年动脉导管未闭患者介入治疗139例分析

目的 分析中老年动脉导管未闭(PDA)患者的临床特征及探讨行经导管封堵治疗的安全性.方法 选择2000年1月至2009年4月在我科介入治疗的139例40岁以上PDA患者,男22例,女117例,年龄40～74(49.8±6.8)岁,术前心功能分级为Ⅰ级64例,Ⅱ级53例,Ⅲ级16例,Ⅳ级6例,分析中老年PDA患者临床特征及观察封堵PDA前后肺动脉压和心功能的改善情况.结果 139例患者中合并肺动脉高压107例,发生率为77.0%,3例严重肺动脉高压者不适宜手术治疗,其余136例均成功行介入治疗,成功率为97.8%.封堵PDA后主动脉造影显示残余分流微量14例,少量2例,中等量分流1例,无手术相关并发症.术后心功能显著改善,肺动脉收缩压由术前(47.3±23.9)mm Hg(1 mm Hg=0.133 kPa)降至(28.1±12.3)mm Hg,肺动脉平均压由(31.7±17.4)mm Hg降至(17.9±8.8)mm Hg(均P<0.01).结论 中老年PDA患者肺动脉高压发生率高,心功能差,经导管封堵中老年PDA是一种安全有效的方法 .     

参附注射液联合左卡尼汀治疗老年慢性充血性心力衰竭的临床研究

目的探讨参附注射液联合左卡尼汀治疗老年慢性充血性心力衰竭患者的临床疗效。方法选取纽约心脏病协会（NYHA）心功能分级Ⅱ～Ⅳ级患者60例,随机分为对照组和治疗组,对照组用常规抗心力衰竭的药物治疗,治疗组在常规药物治疗的基础上加用参附注射液联合左卡尼汀,治疗前后分别测定左室射血分数,左室短轴缩短率,每搏输出量,心输出量和6min步行试验以及安全性指标。结果治疗组和对照组心脏超声检测指标及6min步行试验差异均有统计学意义。结论参附注射液联合左卡尼汀治疗老年慢性充血性心力衰竭安全有效。     

大剂量螺内酯对老年慢性心力衰竭患者心功能和血浆脑钠肽的影响

目的 观察大剂量螺内酯对老年慢性心力衰竭(CHF)患者心功能和血浆脑钠肽(BNP)的影响.方法 选取纽约心脏病协会(NYHA)心功能分级Ⅲ～Ⅳ级的老年CHF患者68例,随机分为试验组和对照组各34例,两组在常规治疗基础上分别给予螺内酯20 mg/d和60mg/d,治疗6个月后评价患者的心功能和检测BNP.结果 试验组血浆BNP浓度由(921.4±284.5)ng/L降低为(316.4±193.3)ng/L(t=14.722,P=0.000);对照组血浆BNP浓度由(904.3±274.0)ng/L降低为(481.3±202.5)ng/L(t=9.271,P=0.000);治疗后两组比较差异均有统计学意义(t=4.280,P=0.011).两组患者治疗前后左室射血分数(LVEF)均改善[试验组(32.2±4.7)％与(45.1±6.2)％,t=6.820,P=0.004;对照组(31.8±5.1)％与(38.3±5.7)％,t=5.283,P=0.008],治疗后两组比较差异也有统计学意义(t=3.844,P=0.017).两组患者治疗前后左室舒张末期内径(LVEDD)缩小[试验组(58.6±4.4) mm与(45.7±4.4)mm,t=5.822,P=0.006;对照组(59.1±5.2) mm与(52.4+4.8) mm,t=3.018,P=0.024],治疗后两组比较差异也有统计学意义(t=3.393,P=0.020).两组治疗前后NYHA心功能分级有明显好转(x2=5.527,P=0.009;x2=4.180,P=0.013).治疗后两组比较差异有统计学意义(x2=3.273,P=0.022).观察组和对照组不良反应发生率分别为11.76％和8.82％(x2=1.063,P=0.116).结论 在常规用药基础上采用大剂量螺内酯可以明显改善CHF患者的心功能,降低BNP水平,可能更适合老年重症CHF患者.     

波生坦治疗特发性肺动脉高压患者的疗效及安全性

目的 观察内皮素受体拮抗剂波生坦治疗中国特发性肺动脉高压患者的有效性、安全性及耐受性.方法 全国多中心Ⅳ期临床试验,共入选79例右心导管等技术确诊的新发特发性肺动脉高压患者,口服波生坦每日2次,每次62.5 mg,治疗4周后增至每日2次,每次125 mg至16周试验结束.分别在基线及治疗16周时记录6分钟步行距离,WHO肺高压功能分级、Borg呼吸困难评分及超声心动图评价资料.结果 波生坦治疗16周后,患者6分钟步行距离从(343.7±93.7)m增至(397.5±104.4)m(P＜0.01),WHO肺高压功能分级显著改善(P＜0.01),Borg呼吸困难评分由3.0±1.5降低至2.5±1.5(P＜0.01),超声心动图估测肺动脉收缩压从(97.8±25.2)mm Hg(1 mm Hg=0.133 kPa)下降至(92.8±29.5)mmHg(P＜0.05).无患者因无法耐受不良反应退出.结论 波生坦能显著改善中国特发性肺动脉高压患者的运动耐量、心功能,且具有良好的安全性和耐受性.

Abstract：

Objective To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH).Methods Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62. 5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class,Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. Results The 6MWD increased from (343. 7 ± 93.7) meters at baseline to (397.5 ± 104. 4) meters after 16 weeks ( P ＜0. 01 ), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P ＜0. 01 ). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8±25.2) mm Hg (1 mm Hg=0. 133 kPa) to (92.8 ±29.5) mm Hg (P ＜0. 05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. Conclusion Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.     

左卡尼汀治疗老年慢性心力衰竭的疗效和安全性

目的 观察左卡尼汀治疗老年慢性心力衰竭的疗效及安全性.方法 老年慢性心力衰竭患者50例,随机均分为2组对照组和左卡尼汀组,两组均给予常规抗心衰治疗,左卡尼汀组同时给予5%GS250 ml加左卡尼汀3 g静脉滴注,1次/d,共15 d,然后口服左卡尼汀1 g/次,2次/d,共15 d.结果 加用左卡尼汀治疗慢性心功能衰竭总有效率为84.0%,显著优于对照组60.0%(P＜0.05),左室收缩功能较常规治疗组有明显改善(P＜0.05),未见明显不良反应.结论 左卡尼汀治疗老年慢性心力衰竭安全有效、无明显毒副作用.     

老年房间隔缺损患者介入治疗的临床分析

目的 探讨老年房间隔缺损患者的临床特征及行经导管封堵治疗的安全性和有效性.方法 入选2000年5月至2010年6月行经导管封堵治疗的(64.5±3.8)岁房间隔缺损患者82例.经导管封堵术中行右心导管检查.术后1d、1个月、3个月和6个月进行随访.分析老年房间隔缺损患者的临床特征,观察房间隔缺损封堵前后肺动脉压及心功能的改变情况.结果 82例房间隔缺损患者中,合并肺动脉高压37例,发生率为45.1％.封堵前的右心导管检查显示,患者肺动脉收缩压为(44.1±12.4)mm Hg(1 mm Hg=0.133 kPa),肺动脉平均压为(25.2 +6.8)mm Hg.1例重度肺动脉高压患者不适宜经导管封堵治疗,其余81例均成功行介入治疗,无手术相关并发症.36例封堵成功的肺动脉高压患者肺动脉收缩压由术前的(52.7±10.3)mm Hg下降至术后的(31.8 +6.3)mm Hg(P＜0.05),肺动脉平均压由术前的(30.9±4.7) mm Hg下降至术后的(21.8±3.4) mm Hg(P＜0.05).与术前比较,术后1d、1个月、3个月和6个月NYHA心功能分级改善.术后新发心房颤动6例.结论 老年房间隔缺损患者通常合并肺动脉高压.只要严格掌握适应证和规范操作,经导管封堵治疗老年房间隔缺损仍是一种安全有效的方法.     

Comparison of patients with pulmonary arterial hypertension with versus without right-sided mechanical alternans

The clinical implications of mechanical alternans in patients with pulmonary arterial hypertension (PAH) remain unknown. In this study, the prevalence, characteristics, and prognostic implications of mechanical alternans in patients with PAH were investigated. Thirty-two consecutive patients with PAH confirmed by cardiac catheterization from 2000 to 2010 were included in this cohort study. During cardiac catheterization, 8 patients (25%) showed mechanical alternans at rest. All alternans were detected in the right ventricle and pulmonary trunk. Serum level of brain natriuretic peptide (584 ± 177 vs 238 ± 252 pg/ml, p = 0.001), World Health Organization functional class (3.5 ± 0.5 vs 2.9 ± 0.4, p = 0.02), mean pulmonary arterial pressure (59 ± 10 vs 47 ± 18 mm Hg, p = 0.03), mean right atrial pressure (10 ± 4 vs 5 ± 4 mm Hg, p = 0.01), right ventricular end-diastolic pressure (15 ± 5 vs 9 ± 5 mm Hg, p = 0.01), and heart rate at catheterization (96 ± 17 vs 70 ± 11 beats/min, p = 0.003) were significantly higher in patients with alternans than in those without. Twelve-month mortality of patients with alternans was higher than in patients without alternans (p = 0.03): the 12-month survival rate after cardiac catheterization was 37% for the alternans group and 75% for the group without alternans. In conclusion, isolated right-sided mechanical alternans is not an uncommon event in patients with PAH. The existence of alternans is associated with the severity of PAH and right ventricular dysfunction and implies a poor prognosis in the short term.     

室间隔缺损和动脉导管未闭合并中重度肺动脉高压的分期复合治疗

目的 评价经导管介入封堵加择期外科手术的分期复合治疗应用于室间隔缺损和动脉导管未闭合并中重度肺动脉高压患者的安全性及有效性.方法 自2004年7月至2009年7月,对22例室间隔缺损和动脉导管未闭合并中重度肺动脉高压患者进行了先经导管介入封堵动脉导管未闭,随后择期行开胸室间隔缺损修补术的分期复合治疗.术后进行随访,观察心律改变、残余分流、封堵器形态、有无瓣膜反流及主动脉狭窄等情况,测量肺动脉压变化,评价治疗效果.结果 经导管介入封堵治疗后,患者肺动脉收缩压由(76.2±25.8)mm Hg(1 mm Hg=0.133 kPa)降至(55.4±20.6)mm Hg(P=0.005),肺动脉平均压由(53.5±23.5)mm Hg降至(36.2±17.8)mm Hg(P=0.049),全肺动脉阻力由(8.2±4.9)wood单位降至(6.9±4.3)wood单位(P=0.037),肺循环血流量与体循环血流量的比值(Qp/Qs)由2.8±2.3升至3.4±1.7(P=0.045).外科手术后,肺动脉收缩压由(64.5±22.3)mm Hg降至(43.1±18.9)mm Hg(P=0.001),肺动脉平均压由(40.2±18.7)mm Hg降至(29.5±15.8)mm Hg(P=0.040).随访中所有患者均未出现右心衰竭和死亡.结论 室间隔缺损和动脉导管未闭合并中重度肺动脉高压的经导管介入封堵加择期外科手术的分期复合治疗安全、有效.

Abstract：

Objective To evaluate the safety and efficacy of staged hybrid approach in treating ventricular septal defect (VSD) patients combined with patent ductus arteriosus (PDA) and pulmonary artery hypertension (PAH). Methods From July 2004 to July 2009, 22 VSD patients with PDA and PAH were enrolled and received staged hybrid approach treatment( transcatheter PDA occlusion and elective open surgery for VSD several lays after PDA occlusion). All patients were followed up to examine rhythm change,residual shunt, shape of occlude, possible valve regurgitation, and aortic stenosis by echocardiography. Results After transcatheter PDA occlusion, pulmonary arterial systolic pressure decreased from (76. 2 ± 25. 8 ) mm Hg ( 1 mm Hg = 0. 133 kPa) to ( 55.4 ± 20. 6 ) mm Hg ( P = 0. 005 ),mean pulmonary artery pressure decreased from ( 53.5 ± 23.5 ) mm Hg to ( 36. 2 ± 17. 8 ) mm Hg ( P=0. 049), total pulmonary resistance decreased from (8. 2 ±4.9)wood units to (6.9 ±4. 3)wood units (P =0. 037), and pulmonary-to-systemic flow ratio (Qp/Qs) increased from 2. 8 ± 2. 3 to 3.4 ± 1.7 ( P = 0. 045 )post transcatheter interventional PDA occlusion. After VSD repair, pulmonary arterial systolic pressure decreased from (64. 5 ± 22. 3 ) mm Hg to (43. 1 ± 18. 9) mm Hg ( P = 0. 001 ) and mean pulmonary artery pressure decreased from (40. 2 ± 18. 7 ) mm Hg to (29. 5 ± 15. 8) mm Hg ( P = 0. 040). There was no death or right heart failure during the follow-up. Conclusion Staged hybrid approach is an effective and safe strategy for treating VSD patients with PDA and PAH.     

Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension

OBJECTIVE: To determine whether lipid microspheres containing prostaglandin E1 (lipo-PGE1) improve pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension (PAH). METHODS: Forty-nine patients with PAH (8 patients with primary pulmonary hypertension, 21 patients with collagen vascular disease, 20 patients with congenital systemic-to-pulmonary shunts) were randomly classified into a conventional therapy group (n = 22) or a group receiving lipo-PGE1 plus conventional drugs (lipo-PGE1 group; n = 27). Echocardiographic pulmonary parameters, New York Heart Association (NYHA) functional class, and Bruce treadmill test results for exercise capacity were recorded before and after treatment. RESULTS: After 2 weeks of treatment with lipo-PGE1 (10 microg bid for 14 days), there were significant improvements in the values (+/- SD) for systolic pulmonary arterial pressure (SPAP) [76.9 +/- 27.9 mm Hg vs 66.5 +/- 22.8 mm Hg, p < 0.001]; total pulmonary resistance (27.2 +/- 13.3 dyne.s.cm(-5) vs 20.2 +/- 10.7 dyne.s.cm(-5), p < 0.001); left ventricular ejection fraction (58.7 +/- 9.6% vs 64.4 +/- 6.8%, p < 0.001); and cardiac output (3.1 +/- 0.8 L/min vs 3.7 +/- 1.1 L/min, p < 0.01). The NYHA functional class decreased from 3.0 +/- 0.6 to 2.5 +/- 0.6 (p < 0.001), and the exercise capacity increased from 2.8 +/- 1.0 to 4.3 +/- 1.3 metabolic equivalents (MET) [p < 0.001]. Compared with the conventional therapy group, the lipo-PGE(1) group achieved significant reduction of SPAP (10.4 +/- 10.3 mm Hg vs 2.2 +/- 5.6 mm Hg, p = 0.002) and a significant elevation of exercise capacity (1.5 +/- 0.9 MET vs 0.6 +/- 1.1 MET, p = 0.018). CONCLUSION: Lipo-PGE1 can decrease pulmonary artery pressure and increase exercise capacity in patients with PAH.     

改良心导管测定大鼠肺血管阻力的方法

目的 建立一种简单、可重复性强的测定正常及肺动脉高压大鼠肺血管阻力的方法.方法 雄性Sprague-Dawley( 180 ～ 200 g)大鼠45只,随机分为3组:正常对照组、低剂量野百合碱组(50 mg/kg)和高剂量野百合碱组(60 mg/kg).给予大鼠颈背部皮下一次性注射野百合碱建立肺动脉高压大鼠模型.大鼠肺动脉压力采用自制改良的末端呈圆弧形的PE- 50导管行右心导管法测定.心输出量利用热稀释法原理检测.肺血管阻力由平均肺动脉压力除心输出量得出.结果 三组大鼠肺动脉压力、心输出量及肺血管阻力的检测总成功率均分别为98％、100％和96％,组间差异无统计学意义.注射野百合碱21 d后,低、高剂量野百合碱组大鼠的平均肺动脉压均显著高于对照组[(43.1±0.8)mm Hg(1 mm Hg=0.133 kPa)、(54.8±2.2) mm Hg比(17.4±1.0) mm Hg,P均＜0.001],且高剂量组明显高于低剂量组(P＜0.001).低、高剂量野百合碱组大鼠心输出量均明显低于对照组[(77.5±6.9) ml/min、(71.0+6.7)ml/min比(126.8±3.9) ml/min,P均＜0.001],低、高剂量组间差异无统计学意义.低、高剂量野百合碱组大鼠肺血管阻力均显著高于对照组[(0.56±0.06) mm Hg·min-1·ml-1、(0.76±0.08)mm Hg·min-1·ml-1比(0.13±0.01)mm Hg- min-1·ml-1,P均＜0.001],且高剂量组明显高于低剂量组(P=0.01).结论 采用此方法检测大鼠肺血管阻力准确、可靠、操作性强,具有推广价值.     

Effects of long-term bosentan in children with pulmonary arterial hypertension

OBJECTIVES: This study investigated the long-term outcome of children with pulmonary arterial hypertension (PAH) treated with bosentan therapy, with or without concomitant prostanoid therapy. BACKGROUND: Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in adults with PAH; however, limited data are available on its long-term effects in children. METHODS: In this retrospective study, 86 children with PAH (idiopathic, associated with congenital heart or connective tissue disease) started bosentan with or without concomitant intravenous epoprostenol or subcutaneous treprostinil therapy. Hemodynamics, World Health Organization (WHO) functional class, and safety data were collected. RESULTS: At the cutoff date, 68 patients (79%) were still treated with bosentan, 13 (15%) were discontinued, and 5 (6%) had died. Median exposure to bosentan was 14 months. In 90% of the patients (n = 78), WHO functional class improved (46%) or was unchanged (44%) with bosentan treatment. Mean pulmonary artery pressure and pulmonary vascular resistance decreased (64 +/- 3 mm Hg to 57 +/- 3 mm Hg, p = 0.005 and 20 +/- 2 U x m2 to 15 +/- 2 U x m2, p = 0.01, respectively; n = 49). Kaplan-Meier survival estimates at one and two years were 98% and 91%, respectively. The risk for worsening PAH was lower in patients in WHO functional class I/II at bosentan initiation than in patients in WHO class III/IV at bosentan initiation. CONCLUSIONS: These data suggest that bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, with or without concomitant prostanoid therapy, is safe and efficacious for the treatment of PAH in children.     

Bosentan for the treatment of adult pulmonary hypertension

Pulmonary hypertension is a severe progressive disease with a marked morbidity and a high mortality attributed to right heart failure. Bosentan, a dual endothelin receptor antagonist, is an effective and well-tolerated oral therapy for the management of pulmonary arterial hypertension (PAH; WHO group 1 pulmonary hypertension). Bosentan improves cardiopulmonary hemodynamics, exercise capacity, WHO functional class and quality of life, as well as delaying time to clinical worsening in patients with PAH. This article reviews the role of endothelin-1 in the pathogenesis and progression of PAH, the diagnosis of PAH and the pharmacology of bosentan, and summarizes the current available evidence for the safety and efficacy of bosentan for the treatment of PAH as a monotherapy and combination therapy, as well as its role in the management of other forms of pulmonary hypertension.     

Bosentan in pulmonary arterial hypertension secondary to scleroderma

OBJECTIVE:. To assess the efficacy and tolerability of bosentan in pulmonary arterial hypertension secondary to systemic sclerosis (SSc-PAH) including patients with restrictive lung disease. METHODS: We retrospectively reviewed 23 SSc-PAH patients with PAH at baseline [PA systolic pressure (PASP) >or= 45 mm Hg by echocardiogram or mean PA pressure > 25 mm Hg at rest by cardiac catheterization], World Health Organization (WHO) functional classes II-IV, and with data available for 18 months. Bosentan dose was 62.5 mg twice daily for 1 month then 125 mg twice daily. Outcomes were WHO functional class, PASP, and pulmonary function tests (PFT) at 3-month intervals for 18 months. RESULTS: WHO class at baseline 3.1 +/- 0.1 (mean +/- SE); 3 months, 2.5 +/- 0.2*; 6 months, 2.4 +/- 0.2*; 9 months, 2.5 +/- 0.2* (*p < 0.02 vs baseline, n = 21 to 23), indicating clinical improvement at 9 months. After 9 months, results were not significant versus baseline. Reduction in WHO class by at least one rank was 57% at 3 months; none worsened. After 9 months, WHO class tended to worsen compared to baseline. Baseline PASP was 54 +/- 2 mm Hg (n = 23) and did not change significantly with therapy. Restriction (total lung capacity 76% +/- 4% of predicted) and reduced diffusing capacity (39% +/- 3% of predicted) were unchanged during therapy. Abnormal transaminases in 2 patients (9%) necessitated discontinuing drug in both. CONCLUSION: Bosentan is clinically beneficial in patients with SSc-PAH including patients with restrictive lung disease, but pulmonary hemodynamics and PFT results remained stable during treatment.     

合并肺动脉高压心脏移植患者术后早期血流动力学分析及处理

目的观察和探讨心脏移植患者术前肺动脉压力和肺循环阻力与术后右心功能不全的关系,及降低因术后早期肺动脉高压造成右心功能损害的临床措施。方法54例接受同种原位心脏移植手术的患者,根据术前肺动脉收缩压（sPAP）≥45nmmHg（1mmHg=0．133kPa）或〈45mmHg,分为Ⅰ组34例和Ⅱ组20例。统计术前血流动力学指标心排指数（CI）、肺循环阻力（PVR）、中心静脉压（CVP）。Swan-Ganz导管连续监测术后60h内的平均肺动脉压（mPAP）、PVR、CI等指标的动态变化。床旁超声分别监测和评价术后3、7、14、21天和1个月时的三尖瓣反流程度。术后肺动脉高压及右心功能维护治疗措施包括利尿、NO吸入、静脉注射前列环素（llomedin 20）、血液滤过等。结果本组患者无术后早期死亡（术后30天内）。Ⅰ、Ⅱ组患者术前的sPAP分别为（60±12）mmHg和（25±9）mmHg（P〈0．01）;PVR分别为（358±150）dyn·s^-1·cm^-5和（140±68）dyn·s^-1·cm^-5（P〈0．01）。术后早期出现右心功能不全的患者Ⅰ组24／34（70．6％）例,Ⅱ组7／20（35．0％）例,两组比较,差异有统计学意义（P=0．01）。Ⅰ组患者术后早期肺动脉压力和PVR仍明显高于Ⅱ组患者,并且在较长的时间后才逐渐下降至正常或仍维持偏高水平。Ⅰ组患者术后早期三尖瓣反流的严重程度高于Ⅱ组患者（P〈0．05）,但随着术后时间的延长,两组患者三尖瓣反流程度差异无统计学意义。结论心脏移植患者术前肺动脉高压的严重程度是影响术后早期右心功能的关键因素。通过有效的降低和防治术后早期肺动脉高压,降低右心负荷,可以明确降低和缩短因肺动脉高压造成术后早期右心功能损害的严重程度和持续时间,有利于术后早期心功能的恢复并维持良好的远期心功能状态。