转移生长因子-β1和C-MYC癌基因在先心肺高压肺血管组织中的表达及意义

目的 研究左向右分流型先天性心脏病（CHD）合并肺动脉高压（PH）肺血管中转化生长因子-β1（TGF-β1）和原癌基因C-MYC的表达与PH病理的关系,探讨其在CHD并PH形成过程中的作用。方法 将112例左向右分流CHD患者按肺动脉平均压（MPAP）高低分为正常组（MPAP〈20 mmHg）33例,PH组（MPAP〉20mmHg）55例,重度PH组（MPAP〉70 mmHg）24例。三组均行肺活检术,免疫组化方法 检测肺血管组织中TGF-β1、C-MYC癌基因的定位及表达情况。结果 TGF-β1主要分布于肺动脉内皮细胞、肺动脉平滑肌和成纤维细胞等细胞的胞质中,且有片状分布。C-MYC癌基因主要分布于肺动脉内皮细胞、肺动脉平滑肌和成纤维细胞等细胞的胞核中。TGF-β1和C-MYC癌基因表达强度（A）随肺小动脉病理分级的加重而升高,在各组之间有明显差异（P〈0.05）,二者表达与病理分级有明显相关性（P〈0.05）。结论 TGF-β1和C-MYC癌基因在CH合并PH的形成过程中起重要生物学作用,TGF-β1对C-MYC癌基因起正性诱导作用,促进平滑肌细胞和成纤维细胞增殖。     

左向右分流型先天性心脏病肺动脉高压患者血小板活化状态及其意义

目的：了解左向右分流型先天性心脏病（先心病）肺动脉高压患者血小板活化状态及其意义。方法：选择左向右分流型先心病患者３０例，其中２０例合并肺动脉高压（Ａ组）；１０例肺动脉压正常（Ｂ组）；选择１０名正常人作对照（Ｃ组）。取外周静脉血，采用放射免疫法测定凝血烷Ｂ２、α－颗粒膜蛋白－１４０和６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）的浓度，采用高效薄层层析法测定血小板激活因子（ＰＡＦ）的浓度。结果：Ａ、Ｂ、Ｃ３组间，６－ｋｅｔｏ－ＰＧＦ１α浓度无显著性差异；Ｂ、Ｃ两组间，凝血烷Ｂ２、α－颗粒膜蛋白－１４０和ＰＡＦ浓度均无显著性差异；Ａ组血浆中凝血烷Ｂ２、α－颗粒膜蛋白－１４０和ＰＡＦ浓度均显著高于Ｂ、Ｃ两组（Ｐ＜０．０５～Ｐ＜０．０１），而且α－颗粒膜蛋白－１４０与肺动脉平均压呈显著正相关（ｒ＝０．５１，Ｐ＜０．０５）。结论：左向右分流型先心病合并肺动脉高压时，存在血小板活化，血浆中凝血烷Ａ２与ＰＡＦ浓度升高以及血小板活化均对左向右分流型先心病肺动脉高压的发展有促进作用。因此，对这些患者给予血小板聚集抑制剂治疗可能是适宜的。     

心脏磁共振成像对左向右分流型先天性心脏病合并肺动脉高压的诊断价值及右心室功能评估

目的 探讨心脏磁共振成像(CMR)对左向右分流型先天性心脏病(CHD)合并肺动脉高压(PAH)的诊断效能及对患者右心室功能的评价作用.方法 选取2012年9月至2020年7月就诊于徐州医科大学附属医院确诊为CHD的42例患者,根据右心导管检查的平均肺动脉压力(mPAP)是否≥25 mmHg将患者分为CHD+PAH组(2...     

左向右分流型先心病肺动脉高压患者呼吸道感染与肺循环血流动力学关系的对照研究

为深讨左向右分流型先心病合并肺动脉高压患者易反复呼吸道感染的原因,我们调查了１０７ 例左向右分流型先心病患者易反复呼吸道感染的发生率,并结合右心导管检查获得的血流动力学参数以及实验室结果,进行了临床对照研究。结果显示：肺动脉高压组或高阻力组易反复呼吸道感染的发生率显著高于肺动脉压正常组或低阻力组;高分流量组与低分流量组易反复呼吸道感染的发生率无显著性差异。易反复呼吸道感染的高发生率组其肺动脉平均压、肺循环总阻力、血浆ＴＸＡ２ 浓度均显著高于低发生率组;而２ 组间左向右分流量无显著性差异。我们认为：１－ 左向右分流量的大小,并不是导致呼吸道易反复感染的根本原因;２－呼吸道症状的产生与血浆ＴＸＡ２ 浓度升高有关     

左向右分流先天性心脏病患儿血浆内皮素-1水平变化及意义

目的 :探讨影响先天性心脏病 ( CHD)患儿血浆内皮素 - 1( ET- 1)水平的因素及临床意义。方法 :选择69例左向右分流的 CHD患儿 ,其中伴肺动脉高压 ( PH) 5 0例 ,轻度 PH17例 ,中度 PH16例 ,重度 PH17例 ;不伴PH 19例。分别采股静脉血 ,伴有中、重度 PH 3 3例患儿随机给予前列腺素 E1 ( PGE1 ,16例 ) 2 0 ng/ ( kg· min)静脉滴注或卡托普利 ( 17例 ) 1mg/ ( kg· d)口服治疗 15 d后再采血 ,用放射免疫法测定样品中 ET- 1含量。结果 :1肺血流量增加 ,血浆 ET- 1水平亦增加 ,达正常对照 2倍多 ( P <0 .0 0 1) ;2 CHD并 PH者血浆 ET- 1水平较无PH者明显增高 ( P<0 .0 0 1) ,ET- 1含量随肺动脉压力的升高而增加 ;3 PGE1 可显著降低 PH患儿的平均肺动脉压 ( P <0 .0 5 )及血浆 ET- 1水平 ( P <0 .0 5 ) ;4卡托普利可使患儿的平均肺动脉压及血浆 ET- 1水平下降 ,但与治疗前比较差异无显著性意义 ( P >0 .0 5 )。结论 :PGE1 和卡托普利可能延缓 PH的发展。     

CHD合并PH患者血浆ET-1浓度与肺血管C-MYC癌基因表达的关系

目的探讨内皮素(ET-1)、C-MYC癌基因在先天性心脏病(CHD)合并肺动脉高压(PH)形成过程中的生物作用。方法42例左向右分流CHD患者,根据肺动脉平均压(MPAP)的高低分为三组,正常组:MPAP<20mmHg,11例;肺动脉高压组:MPAP>20mmHg,22例;重度肺动脉高压组:MPAP>70mmHg,9例。采用放免法测定血浆ET-1浓度。所有病例均行肺活检术,标本常规制成蜡块,应用免疫组化方法,单克隆抗C-MYC基因蛋白抗体作一抗,观察肺组织中C-MYC癌基因的定位及表达。结果C-MYC癌基因主要分布于肺动脉内皮细胞、平滑肌和成纤维细胞等细胞的胞核中。血浆ET-1浓度和C-MYC癌基因表达各组之间差异有统计学意义(P<0.05),各病理分级之间差异有统计学意义(P<0.05),随着肺小动脉病理分级的加重而升高,并且二者的表达与病理分级有明显的相关性(P<0.05)。结论ET-1和C-MYC癌基因在CHD合并PH的形成过程中起着重要的生物学作用,ET-1可以刺激C-MYC癌基因的表达,进而促进平滑肌细胞和成纤维细胞增殖。     

先天性心脏病患者血NT-proBNP浓度与肺动脉高压和导管封堵术的相关性

目的：研究先天性心脏病（CHD）患者血清氨基末端脑钠肽前体（NT-proBNP）浓度与肺动脉平均压（mPAP）的相关性.方法：62例行导管封堵治疗的CHD患者根据mPAP水平被分为四组：CHD不合并肺动脉高压（PAH）组（26例）、CHD合并轻度PAH组（17例）、CHD合并中度PAH组（12例）、CHD合并重度PAH组（7例）,同期选择20例健康体检者作为健康对照组.比较各组介入封堵术前后24h及3个月时的血清NT-proBNP浓度的变化并分析介入封堵术前NT-proBNP浓度与mPAP的关系.结果：与健康对照组相比,术前各CHD组血清NT-proBNP水平明显升高,且随着mPAP升高而显著升高[健康对照组（34.0±16.8）pg/ml比CHD无PAH组（68.0±20.2）pg/ml比轻度PAH组（116.7±43.5） pg/ml比中度PAH组（273.1±64.2）pg/ml比重度PAH组（326.5±50.2） pg/ml,P均＜0.01];直线相关分析显示：62例CHD患者术前血清NT-proBNP浓度与mPAP呈正相关（r=0.604,P=0.002）.各组术后24hNT-proBNP浓度较术前升高,但只有CHD不合并PAH组有统计学差异[（98.9±22.1） pg/ml比（68.0±20.2） pg/ml,P＜0.05],4组术后3个月NT-proBNP浓度较术前均有显著降低（P均＜0.01）.结论：先天性心脏病患者血清NT-proBNP浓度随肺动脉压力升高而逐渐升高,可作为先心病患者肺动脉高压程度以及预后判断的一个指标.     

先天性心脏病患儿血浆ET—1水平影响因素的监测及意义

选择69例左向右分流的先天性心脏病（CHD）患儿抽取股静脉血。其中伴有中、重度肺动脉高压（肺高压）的17例患儿给予卡托普利1mg/(kg.d)口服,治疗15天后再抽血,用放免法测定样品中内皮素-1（ET-1）含量。结果①肺血流量增加,血浆ET-1水平亦增加,达正常对照的2倍多（83.46±24.56pg/ml,38.53±11.93pg.ml,P＜0.001）;②CHD并肺高压者血浆ET-1水平（90.15±22.56pg/ml)较无肺高压者（65.44±6.33pg/ml）明显增高（P＜0.001）,ET-1含量随肺动脉压力的升高而增加;③卡托普利可使患儿的平均肺动脉压及血浆ET-1水平有下降趋势,但与治疗前比较无统计学差异（P＞0.05）。认为卡托普利可预防或延缓肺动脉高压的形成和发展,具有重要的临床意义。     

内皮素、降钙素基因相关肽与先天性心脏病肺动脉压、肺血流量关系的研究

目的 探讨先天性心脏病(CHD)肺动脉高压(PH)的发病机理。方法 采用非平衡放射免疫分析法测定52例肺高压(同伴Qp增加)和30例肺循环血流量(Qp)增加的先心病患儿上腔静脉(SVC)、右心房(RA)、右心室(RV)、肺动脉(PA)、肺静脉(PV)部位血浆ET-1浓度和SVC部位CGRP浓度,18例健康儿童作为对照。结果 血浆ET-1浓度随着PH程度的加重和Qp的增加而升高,ET-1与肺动脉收缩压(SPAP)、全肺阻力(PVP)和Qp呈正相关(r=0.93,0.79,0.65;P<0.01),CGRP则相反(r=-0.90,-0.82,-0.55;P<0.01)。SVC、RA、RV部位间ET-1浓度无显著差异(P>0.05),而RV、PA、PV间ET-1浓度都有显著差异(P<0.01或<0.05)。ET-1与CGRP呈负相关(r=-0.93,P<0.01)。结论 先心病PH和Qp增加皆可导致血浆ET-1浓度升高,PH时更著,升高之来源为肺循环。ET-1促进了先心病PH的形成和发展。Qp增加是PH形成的启动因子。CGRP的浓度下降和CGRP/ET-1的失衡可能是PH发病的另一因素。     

婴幼儿先天性心脏病合并肺动脉高压的手术治疗

对38例3岁以下的先天性心脏病（CHD）合并肺动脉高压（PH）患儿施行外科手术治疗,其中接受体外循环（CPB）手术35例,左腋下小切口动脉导管结扎术3例。结果：全组死亡2例,死亡原因为低心排综合征,PH危象。33例获得随访,随访时间2个月~5 a,心脏超声多普勒检查示2例分别有0.2、0.3 cm分流,其余患儿术后心脏形态及肺动脉压均基本恢复正常,营养发育状况明显改善。认为婴幼儿CHD合并PH一旦确诊,应尽早手术。术中心肌保护和肺保护及围术期监护是手术成功的重要保证。     

Oxygen-mediated pulmonary vasodilation and plasma levels of endothelin-1, atrial natriuretic peptide and cyclic GMP in patients with left-to-right shunt and pulmonary hypertension

This study was performed to evaluate the role of endogenous endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in patients with left-to-right shunt and pulmonary hypertension. Further objectives were to study a possible feedback mechanism between ANP and ET-1 and to examine the influence of ANP on cGMP plasma levels. Finally, the role of these hormones in oxygen-mediated pulmonary vasodilation was examined. Plasma concentrations of ET-1, ANP and cGMP were studied in 39 patients with congenital heart disease and left-to-right shunt. Blood samples were taken from the pulmonary artery and pulmonary vein at cardiac catheterization at baseline and after breathing oxygen for 20 min. Patients were grouped according to the presence or absence of pulmonary hypertension (defined as mean Pp/Ps > or = 0.5). Patients with pulmonary hypertension (n = 18) were found to have significantly higher plasma ANP (665 [59-1358] versus 267 [47-832] pg/ml) and cGMP (21.5 [3.6-82.2] versus 7.8 [0-14.6] nM/L) levels than patients without pulmonary hypertension (n = 21). Pulmonary venous ET-1 plasma concentrations were above normal limits in one patient only. ANP plasma levels were not related to ET-1 and cGMP concentrations. There was no transpulmonary gradient for any of the factors. Pulmonary vasodilation in response to oxygen was found in 7 of 18 patients with PH, but was not associated with significant changes in ET-1, ANP or cGMP plasma concentrations. Patients with congenital heart disease and PH show an increase both in vasoconstrictive and vasodilating factors. The mechanism of oxygen-mediated vasodilation in these patients remains to be elucidated.     

Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation

BACKGROUND. To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years). METHODS AND RESULTS. Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure. CONCLUSIONS. Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.     

先天性心脏病重度肺动脉高压对腺苷的急性反应

目的: 探讨先天性心脏病（CHD）并发重度肺动脉高压（PAH）患者对腺苷的急性血流动力学反应。方法: 对25例CHD并发严重PAH患者采用腺苷进行急性肺血管扩张试验,检测其血流动力学指标变化。结果: 25例患者中,仅7例患者达到最大剂量无不良反应。给予腺苷后,肺动脉压力和主动脉压力均显著降低（P<0.05）,股动脉血氧饱和度,肺血管阻力,肺循环/体循环血流量比值,肺动脉/主动脉平均压比值,肺血管阻力/体循环阻力比值（Rp/Rs）均无明显变化。没有患者肺动脉平均压降至40 mmHg以下。12例患者肺血管阻力和Rp/Rs降低10%以上,与另外13例患者比较,二者在年龄,肺动脉压力,肺动脉/主动脉平均压比值,肺循环/体循环血流量比值,肺血管阻力和Rp/Rs等方面均无明显差异。结论: 在CHD并发重度PAH患者中,采用腺苷进行急性肺血管扩张试验可引起肺动脉和体循环压力同步降低,而对肺血管阻力无明显影响。     

心血管调节肽与先天性心脏病肺动脉高压相关关系的研究

目的本文研究两种心血管调节肽--神经肽Y(NPY)、降钙素基因相关肽(CGRP)和肿瘤坏死因子(TNF)与先天性心脏病(先心病)肺动脉高压(肺高压)的关系;并检测血清CGRP、NPY浓度作相关分析,以判断它们是否具有相关性.方法采用放射免疫法测定80例先心病患儿[13例为非肺高压组,67例为肺高压组(同时根据肺高压的程度又分为轻、中、重度患儿)]血清NPY、CGRP及TNF浓度,将2组进行比较,应用统计学方法进行方差分析,t检验.结果非肺高压组与肺高压组轻、中、重度患儿血清NPY及CGRP浓度均存在显著性差异(P＜0.01).手术前后肺高压组轻、中度患儿NPY和CGRP浓度存在显著性差异(P＜0.01),而肺高压组重度者差异不明显;肺高压组外周血NPY与CGRP浓度存在负相关关系.结论3种活性物质在先心病肺高压的发生机制中有重要的作用,NPY/CGRP值的升高参与和促进了肺高压的形成和发展.     

先天性心脏病患者免疫因子Th17/Treg失衡与肺动脉高压的关系

目的:探讨患者外周血中Th17细胞、CD4+D25+FoxP3+调节性T细胞(Treg)的变化及意义。方法:75例先天性心脏病(CHD)合并肺动脉高压(PAH)患者,分为轻度肺动脉高压组(28例)、中度肺动脉高压组(32例)及重度肺动脉高压组(15例),20例健康体检者作为对照组。采用流式细胞分析法检测外周血中Th17细胞、Treg细胞占CD4+T细胞的比例,分析Th17细胞与Treg细胞的比例与肺动脉压的相关性。结果:Th17/CD4+T细胞比例、Treg/CD4+T细胞的比例和Th17/Treg细胞比值,两组间差异具有统计学意义(P<0.05),随着肺mPAP的增加,Th17/CD4+T细胞比例明显升高;Treg/CD4+T细胞的比例明显下降;Th17/Treg细胞比值显著升高。mPAP与Th17/Treg比值呈显著正相关(r=0.95,P<0.05)。结论:先天性心脏病合并肺动脉高压患者外周血中存在Th17/Treg失衡,且与肺动脉高压程度呈正相关,Th17/Treg失衡可能参与了肺动脉高压的发生发展。     

Plasma cyclic 3',5'-adenosine monophosphate in patients with elevated pulmonary pressure due to left-to-right shunt

Background

Increased pulmonary blood flow in patients with left-to-right shunt has been shown to be associated with alterations in prostacyclin-synthesis. There are limited data with respect to the plasma cAMP in patients with elevated pulmonary artery pressure due to left-to-right shunt. We hypothesized that plasma cAMP might be influenced by pulmonary blood flow or pressure in patients with left-to-right shunt.

Methods

Plasma cAMP from venous blood was measured in 122 healthy controls aged 8.3 (0.2 - 14.9) years (median [range]) and in 130 patients with left-to-right shunt aged 1.4 (0.1 - 19.1) years by radioimmunoassay.

Results

Plasma cAMP in controls and in patients was similar and decreased with age. Healthy infants (n = 42) showed higher plasma cAMP (46 [27-112] nmol/l) than children > 6 years of age (n = 40, 39 [19-73] nmol/l; P < 0.001).

Conclusions

These values should be taken into consideration when reporting plasma values for cAMP in patients with congenital heart disease. The values for healthy children obtained in this study should allow a better interpretation of plasma cAMP levels in various disease conditions such as chronic renal failure, liver chirrhosis, hyperthyreosis, or children with intellectual disability.     

Assessment of pulmonary hypertension in the pediatric catheterization laboratory: Current insights from the magic registry

Objectives: To assess protocols, demographics, and hemodynamics in pediatric patients undergoing catheterization for pulmonary hypertension (PH). Background: Pediatric specific data is limited on PH. Methods: Review of the Mid‐Atlantic Group of Interventional Cardiology (MAGIC) collaboration PH registry dataset. Results: Between November 2003 and October 2008, seven institutions submitted data from 177 initial catheterizations in pediatric patients with suspected PH. Pulmonary arterial hypertension associated with congenital heart disease (APAH‐CHD) (n = 61, 34%) was more common than idiopathic PAH (IPAH) (n = 36, 20%). IPAH patients were older with higher mean pulmonary arterial pressures (mPAP) (P < 0.01). Oxygen lowered mPAP in patients with IPAH (P < 0.01) and associated PAH not related to congenital heart disease (APAH‐non CHD) (P < 0.01). A synergistic effect was seen with inhaled Nitric Oxide (iNO) (P < 0.01). Overall 9/30 (29%) patients with IPAH and 8/48 (16%) patients with APAH‐non CHD were reactive to vasodilator testing. Oxygen lowered pulmonary vascular resistance index (PVRI) in patients with APAH‐CHD (P < 0.01). There was no additive effect with iNO but a subset of patients required iNO to lower PVRI below 5 WU·m². General anesthesia (GA) lowered systemic arterial pressure (P < 0.01) with no difference between GA and procedural sedation on mPAP or PVRI. Adverse events were rare (n = 7) with no procedural deaths. Conclusions: Pediatric patients with PH demonstrate a higher incidence of APAH‐CHD and neonatal specific disorders compared to adults. Pediatric PH patients may demonstrate baseline mPAP < 40 mm Hg but > 50% systemic illustrating the difficulty in applying adult criteria to children with PH. Catheterization in children with PH is relatively safe. © 2010 Wiley‐Liss, Inc.     

Aetiological distribution of pulmonary hypertension and the value of transthoracic echocardiography screening in the respiratory department: A retrospective analysis from China

Methods

The aetiological composition and clinical characteristics of patients with pulmonary hypertension (PH) hospitalised in the respiratory department were retrospectively analysed, as well as the correlation between transthoracic echocardiography (TTE) and right heart catheterization (RHC) for evaluating pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (mPAP).

Results

Of 731 patients, 544 (74.42%) were diagnosed with PH by RHC. Pulmonary arterial hypertension (PAH) was the most common type of PH, accounting for 30.10%; PH due to lung disease and/or hypoxia accounted for 20.79%, and PH due to pulmonary artery obstructions accounted for 19.29%. TTE has the highest specificity for diagnosing PH due to pulmonary artery obstructions. The specificity was 0.9375, the sensitivity was 0.7361 and the area under the ROC curve (AUC) was 0.836. PASP, and mPAP estimated by TTE were different for various types of PH. In terms of PASP, TTE overestimated PASP in PH due to lung disease and/or hypoxia, but there was no significant difference compared with RHC (P > 0.05). TTE underestimates PAH patients' PASP compared with RHC. In terms of mPAP, TTE underestimated the mPAP of all types of PH, as there was a significant difference in the TTE-estimated mPAP of patients with PAH compared with RHC but not on other types of PH. Pearson correlation analysis of TTE and RHC showed a moderate overall correlation (rPASP 0.598, P < 0.001; rmPAP 0.588, P < 0.001).

Conclusions

Among the patients with PH in the respiratory department, patients with PAH accounted for the majority. TTE has high sensitivity and specificity for the diagnosis of PH due to pulmonary artery obstructions in the respiratory department.