磷酸二酯酶5抑制剂治疗先天性心脏病合并肺动脉高压

肺动脉高压在先天性心脏病中很常见,有效地降低患儿肺血管阻力,能够改善其远期生存率.对肺动脉高压病理生理的研究发现,使用磷酸二酯酶5抑制剂可使肺血管舒张,降低肺血管阻力.目前磷酸二酯酶5抑制剂西地那非在国外已用于治疗肺动脉高压.多个临床试验已经证明磷酸二酯酶5抑制剂能够显著降低肺血管阻力,改善患者远期生存率和生活质量,且能较好地被患者耐受.     

先天性心脏病并重症肺动脉高压的性质评价

根据上海市两个区活产婴儿前瞻性调查 ,先天性心脏病(先心病 )发病率为 6 .78‰ ,估计我国每年新出生先心病患儿达 15万左右。其中肺动脉高压 (PH)为左向右分流型先心病及部分复杂性重症先心病常见和严重并发症之一 ,如不及时治疗 ,将发展成器质性PH ,直接影响病人预后及外科手术效果或介入治疗指征的选择。发达国家由于对这些病人早期进行手术治疗 ,发展成重症PH少见 ,而我国由于地域广阔 ,经济发展不平衡 ,虽然近年小儿心血管诊断与治疗获长足的进展 ,但我国还有为数不少伴重症PH病人未能得到及时治疗 ,以致影响治疗效果或失去手术机…     

Babybodyplethysmography in infants and children with congenital heart disease and pulmonary hypertension

We investigated pulmonary mechanics in 46 children (27 males, 19 females) with congenital heart defects with left-to-right shunt and pulmonary hypertension. Patients ranged in age from 6 weeks to 4 years. Babybodyplethysmography studies were performed before corrective heart surgery, and again at 2 weeks and 6 months after surgery. Preoperative pulmonary function data were compared to hemodynamic data obtained during cardiac catheterization: pulmonary artery pressure, oxygen saturation, and ratios of pulmonary to systemic blood flow (Qp/Qs) and vascular resistance (Rp/Rs). Airway resistance was elevated before surgery to 148% of predicted and it dropped significantly to normal levels, 104% of predicted, only 6 months after surgery. Functional residual capacity (FRCpleth) was increased to 127% of predicted before surgery and normalized significantly to 101% of predicted within the same time period. On the other hand, breathing frequency and minute volume, indexed to body weight, decreased significantly in the 2 weeks after surgery. Statistical analysis of the hemodynamic data and lung function tests showed only a poor linear correlation between functional residual capacity and oxygen saturation in the pulmonary artery (r=0.26–0.37) and the Rp/Rs ratio (r=0.38). Airway resistance also correlated poorly with the Qp/Qs and Rp/Rs ratios (both r=0.29). In young children with heart defects with increased pulmonary blood flow and pulmonary hypertension, lung mechanics are abnormal leading to bronchial obstruction and hyperinflation. Additional studies of dynamic lung compliance and elastance will be needed to look for interstitial lung alterations in these patients.     

先天性心脏病并肺动脉高压119例

目的 分析总结119例CHD并肺动脉高压(PAH)患儿的诊疗经过及随访情况,以提高对该病的治疗效果.方法 回顾性分析2005年1月至2010年12月收治的119例CHD并PAH患儿的临床资料及相关辅助检查,年龄1个月～15岁[(42.4±2.8)个月].患儿接受药物治疗、介入治疗或外科手术治疗等综合治疗.出院后定期门诊随访,监测症状、体征及辅助检查(胸片、心脏彩超).结果 119例患儿中66例接受介入治疗,其中1例术后1d发生溶血,最终全部治愈出院.53例患儿接受外科手术治疗,其中49例经积极治疗后好转出院,术后发生切口感染1例,上呼吸道感染8例,心律失常8例,并肺炎1例;住院死亡4例,分别死于低心排综合征和PAH危象.治疗后全组患儿肺动脉压力8～90 mmHg[(20.23 ±7.13) mmHg(1 mm Hg=0.133 kPa)],与治疗前比较差异有统计学意义(t=3.812,P＜0.01),其中肺动脉压力下降＞40 mm Hg 79例(66.4％).17例并重度PAH者,经术前药物控制后行外科手术,术后14例(82％)肺动脉压力较术前下降＞20 mm Hg,2例出现低心排综合征,1例出现PAH危象.全组患儿经治疗后肺动脉压力、心胸比、心腔大小、左心收缩功能均较治疗前改善.结论 对CHD并PAH患儿应加强早期诊断,及时选择介入或手术治疗时机,对于中重度PAH者适时把握手术指征,以提高治愈率及改善生存质量.     

P选择素在先天性心脏病肺动脉高压中的变化

先天性心脏病(简称先心病)患者存在止血功能的异常,容易发生血栓形成和出血,血小板的活化是导致其止血功能异常的重要因素。P选择素是研究中最广泛应用的颗粒膜蛋白活化依赖性单克隆抗体,存在于静息血小板α颗粒和内皮细胞 Weibel-Palade小体中,激活后转移至浆膜表达,为     

吸入一氧化氮治疗先天性心脏病术后肺动脉高压

目的评价吸入一氧化氮(NO)在左向右分流性先天性心脏病(先心病)术后严重肺动脉高压的治疗效果。方法81例先天性心脏病患儿术后予以吸入NO治疗,治疗指征:肺/体动脉收缩压之比(Pp/Ps)>0.5,氧合指数(PaO2/FiO2)<150mmHg,传统降肺动脉压治疗无效。初始吸入浓度为20×10-6vol/vol,根据血气及血流动力学情况进一步调整,不超过45×10-6vol/vol,同时监测二氧化氮(NO2)浓度及高铁血红蛋白浓度。结果81例吸入NO治疗后肺动脉压力明显下降,从(54.0±15.8)mmHg降至(45.7±12.8)mmHg(P<0.01),而体动脉压力无明显变化,同时PaO2/FiO2明显改善,从100.6±40.1升至135.8±29.7(P<0.01)。监测NO2浓度<1×10-6vol/vol,高铁血红蛋白浓度<2%。未发现明显出血及其他不良反应。结论吸入NO治疗可以安全有效地降低肺动脉压力,提高氧合指数,从而改善先心病合并肺动脉高压的预后。     

小儿先天性心脏病合并肺动脉高压的药物治疗

先天性心脏病的患儿常合并有肺动脉高压,对于病程的变化和手术及药物治疗方案产生很大的影响。目前随着药物学的发展,临床上逐渐采用了诸如一氧化氮、磷酸二酯酶抑制剂、前列腺素类药物和内皮素拮抗剂等药物,配合先天性心脏病手术,通过单独给药和联合给药的方式,针对术前和术后的肺动脉高压进行治疗,已经取得了良好的效果。文章对这些药物各自的特点和应用进行综述。     

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目的 探讨雾化吸入伊洛前列素进行急性血管扩张试验的价值.方法 研究对象为2007年2月至2008年5月在广东省心血管病研究所住院的50例先天性心脏病合并肺动脉高压患儿,对所有患儿进行左右心导管检查,之后肺动脉内注射酚妥拉明或雾化吸入伊洛前列素进行急性血管扩张试验,试验后重复左右心导管检查.根据Fick公式计算血流动力学参数.综合判断肺动脉高压性质,将惠几分成两组:动力组和梗阻组.动力组患儿进行手术治疗,术后定期随访并修正术前诊断.结果 酚妥拉明会显著增高受试者的心率,而伊洛前列素对心率的影响较轻微;酚妥拉明和伊洛前列素都能够降低平均肺动脉压力和肺血管阻力,升高肺循环血流量;酚妥拉明同时会降低平均主动脉压力和体循环阻力,升高体循环血流量,而伊洛前列素对体循环没有明显的影响.在使用伊洛前列素的急性血管扩张试验中,平均肺动脉压力、肺血管阻力/体循环阻力和肺循环血流量/体循环血流量等参数的变化在动力组和梗阻组中差异无统计学意义(P值分别为0.016、0.024和0.030).而使用酚妥拉明的急性血管扩张试验中,平均肺动脉压力和肺血管阻力两项参数的变化在动力组和梗阻组中差异有统计学意义(P值分别为0.017和0.004).结论 在先天性心脏病合并肺动脉高压的患儿中,使用酚妥拉明或伊洛前列素进行急性血管扩张试验都能够有效区分动力性与梗阻性肺动脉高压.酚妥拉明用药前后,肺循环和体循环的压力、阻力和血流量都有明显变化.而伊洛前列素雾化吸入以影响肺循环为主,可以保持相对平稳的血流动力学,在安全性上优于酚妥拉明.     

Increased turnover of serotonin in children with pulmonary hypertension secondary to congenital heart disease

Serotonin (5HT) is a potent vasoconstrictor of the pulmonary vascular bed and may be involved in the pathophysiology of secondary pulmonary hypertension in children with a left-to-right shunt due to a congenital heart defect. To test this hypothesis we measured the total and free 5HT concentration in blood as well as the urinary excretion of its main metabolite 5-hydroxyin-doleacetic acid (HIAA) in children showing a left-to-right shunt with (n=10) and without (n=18) pulmonary hypertension. 5HT and HIAA were also measured in children after corrective cardiac surgery using cardiopulmonary bypass (n=14) and in controls without congenital heart disease (n=18). The concentrations of total and free 5HT were not significantly different between controls and patients with a left-to-right shunt. After cardiac surgery total 5HT concentration was significantly reduced by about 65% owing to a postoperatively reduced platelet count. In patients with a left-to-right shunt the total 5HT content was similar in the right atrium (204.0±17.3 ng/ml), pulmonary artery (189.0±19.1 ng/ml), and aorta (195.0±19.3 ng/ml), as was the free 5HT concentration. Therefore no net release of 5HT from platelets occurred between these sampling sites. In patients with pulmonary hypertension, the urinary excretion of HIAA was significantly increased when compared with controls and patients without pulmonary hypertension. It is concluded that turbulent blood flow in children with a left-to-right shunt does not lead to a significant release of 5HT from platelets. However, the increased urinary excretion of HIAA in patients with pulmonary hypertension indicates an increased turnover of 5HT, probably due to an increased number of intrapulmonary neuroepithelial cells or a higher metabolic rate of 5HT within those cells.     

先天性心脏病合并肺动脉高压的诊断及治疗

肺动脉高压 (ｐｕｌｍｏｎａｒｙｈｙｐｅｒｔｅｎｓｉｏｎ ,ＰＨ)定义[1] 是肺动脉收缩压 (ＰＡＳＰ)超过 4 0 0ｋＰａ或肺动脉平均压 (ＰＡＭＰ)超过 2 6 7ｋＰａ。它是左向右分流型先天性心脏病 (ＣＨＤ)常见的严重并发症 ,其严重程度直接影响疾病的治疗及预后。近年来 ,对小儿肺动脉高压的基础理论研究和临床研究已取得突飞猛进的进展 ,随着对ＰＨ病理生理机制的深入研究 ,ＰＨ的无创性诊断方法也趋于成熟并得到广泛应用 ,一些新的降低肺动脉压力的药物已在临床上应用并取得了很好的效果。1　肺动脉高压的无创性诊断1.1　临床症状　当…     

先天性心脏病肺动脉高压肺组织超微结构的改变及临床意义

目的　探讨先心病肺动脉高压 (PH)患儿肺组织超微结构的改变及其临床意义。方法　 2 1例先心病患儿为 1997年 11月～ 1999年 2月间住院行心血管手术者 ,全组平均肺动脉压为 (5 8± 2 1)mmHg ,肺血管阻力 (760± 2 0 6)dyn·s·cm-5。除 4例动脉导管未闭 (PDA)行导管结扎外 ,其余患儿均在体外循环下行心内直视手术 ,于开胸后立即取肺组织在电镜下观察肺组织超微结构的变化。结果　 2 1例PH患儿肺组织均有不同程度的纤维化 ,且在毛细血管两侧不对称 ,主要集中于非气血交换侧 ,以胶原纤维增生最显著 ,弹力纤维增生次之。肺泡Ⅱ型细胞显著增多 ,其胞质内可见大量的线粒体、粗面内质网 ,板层小体增多并可见其内容物丢失。肺泡Ⅰ型细胞基膜显著增厚 ,肺小动脉平滑肌细胞增生 ,毛细血管基膜增厚。结论　重症先心病PH患儿肺组织超微结构发生明显改变 ,结合临床 ,提示对于先心病患儿宜尽早手术纠治 ,以从根本上消除形成PH的条件。     

西地那非治疗儿童先天性心脏病术前或术后合并肺动脉高压近期疗效和安全性的系统评价

目的 评价西地那非治疗儿童先天性心脏病（CHD）术前或术后合并肺动脉高压(PAH)的近期疗效和安全性。方法 检索Cochrane临床对照试验库（CENTRAL）、EMBASE、PubMed、在研对照试验数据库、中国生物医学文献数据库、中国期刊全文数据库和中文科技期刊全文数据库。检索时间均从建库至2011年3月。并手工检索相关会议论文集并追查纳入文献的参考文献,获得西地那非治疗儿童CHD术前或术后合并PAH的RCT文献。采用Cochrane评价手册5.0推荐的方法评价纳入文献的方法学质量。用RevMan 5.0软件进行Meta分析,对无法合并分析的结果进行描述性分析。结果 共检索到相关文献130篇,其中3篇RCT文献进入系统评价。1篇文献存在低度偏倚风险,2篇文献存在高度偏倚风险。①西地那非组与安慰剂组或常规治疗组出院前病死率差异无统计学意义（RR=0.09,95％CI：0.01～1.64）。②西地那非组PAH危象发生率低于常规治疗组;西地那非组治疗40 min后平均肺动脉压显著低于安慰剂组或常规治疗组（MD=-9.1 mmHg,95%CI:-11.3~ -6.9 mmHg）和前列腺素E1组（MD=-5.1 mmHg,95%CI:-7.6~ -2.7 mmHg ）;肺动脉收缩压显著低于安慰剂组或常规治疗组,MD=-11.2 mmHg,95%CI:-16.5~ -5.9 mmHg;③西地那非组与安慰剂组或常规治疗组住院时间差异无统计学意义,机械通气时间和重症监护时间显著低于安慰剂组。④西地那非组治疗40 min后氧合指数显著高于安慰剂组或常规治疗组,MD=66.0,95%CI:35.7~96.3。⑤西地那非组治疗40 min后平均体循环动脉压稍有下降,MD=-4.3 mmHg,95%CI:-7.8~-0.8 mmHg。⑥2篇文献报道无药物相关死亡及不良反应的发生;1篇文献报道10例患儿发生不良反应,主要为短暂阴茎勃起、暂时性鼻阻塞和胃肠道反应,在停用西地那非后均恢复。结论 西地那非能有效降低CHD术前或术后合并PAH患儿的肺动脉压,且短期使用有较好的安全性。鉴于纳入文献数量较少且质量偏低,对于西地那非确切疗效的评价还需要大样本和高质量的RCT研究进一步证实。     

先天性心脏病合并肺动脉高压时肺组织病理与免疫组化研究

为探究先天性心脏病（先心病）伴肺动脉高压（肺高压，PH）患儿肺组织一氧化氮合酶（eNOS)的表达有否改变，随机选择法洛四联症（tetralogy of Fallot,TOF)、单纯室间隔缺损(ventricular septal defect,VSD)/房间隔缺损（atrial septal defect,ASD)、先心病合并PH患儿48例，分成3组，取少许右肺中叶组织，利用免疫组织化学法对eNOS进行半定量分析。结果显示先心病伴PH组患儿肺组织内皮细胞内的eNOS染色明显弱于TOF组和单纯VSD／ASD组患儿（P＜0．01）。提示先心病PH组肺组织的eNOS含量水平低下，造成内源性NO生成减少，为临床吸入NO治疗PH提供了理论依据。     

Risk of pulmonary tuberculosis in children with congenital heart disease

Children with low-flow congenital heart lesions are reported to have an increased incidence of pulmonary tuberculosis. The aim of this study was to investigate if children with congenital heart disease have an increased incidence of pulmonary tuberculosis and to determine if patients with certain heart conditions are more susceptible to pulmonary tuberculosis than others. This retrospective study over a 6-year period showed that pulmonary tuberculosis was 2.5-fold more common in children with congenital heart disease than in normal children from the same community. Children with congenital pulmonary stenosis had a prevalence equal to those with acyanotic (ventricular and atrial septal defects) and cyanotic (transposition of the great arteries) high-flow heart lesions, whereas there were no cases of tuberculosis in children with low-flow cyanotic heart lesions such as tetralogy of Fallot. Cardiac surgery had to be postponed as a result of pulmonary tuberculosis in 7.2% of all patients in whom it was required. Over the 6-year period of the study, cardiac surgery had to be delayed in 60% of cases with pulmonary tuberculosis and congenital heart lesions so antituberculosis therapy could be completed. Physicians treating children with congenital heart lesions should maintain a high index of suspicion for the development of pulmonary tuberculosis, especially in those with acyanotic and cyanotic high-flow lesions and pulmonary stenosis.     

先天性门体静脉分流相关性肺动脉高压5例临床分析

目的探讨儿童先天性门体静脉分流相关性肺动脉高压(PAH-CPS)的临床特点。方法回顾分析2012年1月至2019年1月收治的PAH-CPS患儿的临床资料。结果共5例患儿,男2例、女3例,初诊年龄0.08～4.4岁。主要表现为反复肺部感染、肝脾大、肝功能异常、肺动脉高压。超声心动图检查明确患儿均有不同程度肺动脉高压、合并心内畸形。腹部超声示肝内外门体静脉分流。腹部增强CT和心导管造影可显示肝内外血管的走形和发育。结论 PAH-CPS可表现为反复肺部感染、肝脾肿大、肝功能异常等;超声检查可提供诊断线索,腹部增强CT扫描、心导管造影可明确诊断。     

Non-congenital heart disease associated pediatric pulmonary arterial hypertension

Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged.     

前列地尔对先天性心脏病合并重度肺动脉高压的治疗作用

目的观察前列地尔脂微球载体制剂(LipoPGE1,商品名:凯时)对高肺血流性先天性心脏病(先心病)患儿的肺循环和体循环压力及阻力的影响作用。方法将50例先心病合并重度肺动脉高压的患儿随机设为治疗组(25例),于右心导管检查术中直接静脉推注凯时及对照组(25例),推注立其丁,观察肺动脉(PA)、主动脉(AO)、肺毛细血管(PW)压力,以及肺循环阻力、体循环阻力和心率的改变。结果凯时能有效降低PA压力(P<0.001),对AO压力和心率影响不明显;而立其丁在降低PA压力的同时,也使AO压力下降,并明显加快心率(P均<0.001)。结论对于先心病合并肺动脉高压的患儿,凯时可能是一种比较理想的选择性降低PA压力的制剂。     

Outcomes of neonates with congenital heart disease

One of the most important advances of the past 10 to 15 years in the field of pediatric cardiology is the improvement in prognosis for neonates with complex congenital heart disease. During the past 18 months, several publications have addressed outcomes in neonates with congenital heart disease. Many of these reports demonstrate continuing improvement in preoperative, early postoperative, and late postoperative survival among patients with complex neonatal heart defects. Other reports shed substantial new light on late functional outcome, especially neurodevelopmental status. In addition to data on survival, morbidity, and functional status, we discuss developments in perioperative evaluation and management that are likely to further the trend toward improved outcome for neonates with complex congenital heart disease.     

先天性心脏病并肺动脉高压患儿血清一氧化氮和血浆内皮素变化的意义

目的　探讨血清一氧化氮 (NO)和血浆内皮素 1(ET 1)对先天性心脏病 (CHD)患儿肺动脉高压 (PH)形成的影响。方法　选择健康儿童 3 0例为对照组 (A组 ) ;3 0例肺动脉压正常的CHD患儿为B组 ;3 0例CHD并PH患儿为C组。采用硝酸还原法对其血清NO 2 /NO 3 、放免法对其血浆ET 1浓度进行测定。结果　B组血清NO 2 /NO 3 浓度较A组明显增高 ;C组血清NO 2 /NO 3 浓度较A组低 ;无论是否并PH ,A、B两组与对照组相比 ,其血浆ET 1浓度均增高。结论　血清NO 2 /NO 3 浓度和血浆ET 1浓度及其间平衡关系共同影响PH的形成及其程度