肺动脉高压研究进展

近年来有关肺动脉高压及右心功能方面的研究已成为国内外学术热点,欧洲心脏病学会(ESC)和美国心脏病学会基金会(ACCF)/美国心脏学会(AHA)相继发表了新的肺动脉高压诊断和治疗指南(共识).现简要介绍新的指南,并就肺动脉高压的基础研究、临床治疗以及肺动脉高压与右心的相关研究进展进行综述.     

弹性蛋白与肺动脉高压的肺血管重建

肺动脉高压是先天性心脏病及慢性缺氧性肺病的常见并发症,并决定它们的预后,其发病机理不明。肺动脉壁弹性蛋白离解增加及细胞外基质弹性蛋白含量的变化是肺动脉高压的共同特征,对此研究有望成为今后肺动脉高压研究的方向。本文对近年来弹性蛋白与肺动脉高压的相关研究作一综述。     

肺动脉高压患者的预后评估

肺动脉高压是发病率较低、预后较差的肺血管疾病.近10余年来,随着靶向治疗药物的应用,肺动脉高压的生存率较前有明显的改善;多个登记注册研究和一些临床研究结果的发布,促使对肺动脉高压预后相关的因素有了更加全面的认识.现简要综述各预测因素在肺动脉高压预后评估中的作用,以及肺动脉高压预后模型的建立.     

新生儿持续性肺动脉高压、先心相关肺动脉高压造成心脏损伤的情况对比分析

目的 对比新生儿持续性肺动脉高压与先天性心脏病相关肺动脉高压在心脏损伤方面的情况。方法 根据入选标准收集2018年1月至2021年12月我院新生儿病房100例符合肺动脉高压的患儿作为本次研究对象,根据疾病类型分为持续性肺动脉高压组与先天性心脏病相关肺动脉高压组,对比两组患儿围生期的基线资料、超声心动图指标以及心肌酶。结果 两组患儿性别、平均胎龄、平均体质量、母亲年龄、分娩方式、窒息发生情况、胎膜早破、母亲妊娠期合并症、母亲吸烟等基线资料比较,差异均无统计学意义（P>0.05）;持续性肺动脉高压组患儿LA、LV低于先天性心脏病相关肺动脉高压组,LVDd、LVEF高于先天性心脏病相关肺动脉高压组（P<0.05）;两组患儿RA、RV、RVDd无显著差异（P>0.05）;先天性心脏病相关肺动脉高压组患儿CK、CK-MB高于持续性肺动脉高压组（P<0.05）。结论 先天性心脏病相关肺动脉高压患儿左心室、左心房及左室射血分数改变较为明显,且对患儿心脏损伤程度相比持续性动脉高压更重。     

经胸多普勒心脏超声对肺动脉高压患者诊断价值的荟萃分析

作为内科系统的一种常见疾病,肺动脉高压的诊断一直是临床难题.右心漂浮导管虽然是诊断肺动脉高压的金标准,但由于其为有创检查且易发生并发症,限制了临床广泛使用.经胸多普勒心脏超声是最常用的诊断肺动脉高压的无创手段,但其在肺动脉高压诊断中的价值却存在争议.为此,我们检索了PubMed、Web of Science和Ovid数据库中研究采用经胸多普勒心脏超声用于诊断肺动脉高压的文献,应用诊断性试验荟萃分析研究方法对相关文献进行质量评估,提取纳入诊断相关数据,运用荟萃分析定量分析经胸多普勒心脏超声在肺动脉高压患者中的诊断价值.     

特发性肺动脉高压相关SOX17基因新突变分析

目的:寻找特发性肺动脉高压相关SOX17基因新突变。方法:收集58例特发性肺动脉高压患儿和200名健康对照者的临床资料及血标本,纯化基因组DNA。测序分析研究对象的SOX17基因以发现致特发性肺动脉高压突变。利用在线计算机程序分析突变氨基酸在物种进化上的保守性及其致病性。结果:在2例特发性肺动脉高压患儿中各发现1种SOX17基因新突变,分别为c.232TA和c.281AT突变,即p.Trp78Arg和p.His94Leu突变。该突变不存在于200名健康对照者。数据分析表明突变氨基酸在多物种进化上完全保守且均具有致病性。结论:特发性肺动脉高压相关SOX17基因新突变对特发性肺动脉高压患者的遗传咨询及精准防治具有潜在的临床意义。     

骨生成蛋白及其受体信号途径和肺动脉高压

肺动脉高压主要与血管效应器失调、相关疾病及遗传因素有关。近年来研究发现,在所有的家族性肺动脉高压患者和40%的特发性肺动脉高压患者中,骨形成蛋白受体Ⅱ基因发生突变。本文对骨形成蛋白及其受体途径与特发性肺动脉高压的关系作一综述。     

阻塞性睡眠呼吸暂停综合征能否引起肺动脉高压

2003年在威尼斯举行的第3届世界肺动脉高压会议修订了肺动脉高压的分类.新分类依然强调了和肺部疾病及缺氧相关的肺动脉高压,其中就包括了睡眠呼吸障碍.按照2005年第2版睡眠疾病国际分类,睡眠呼吸疾病是一组疾病,包括4类:中枢性睡眠呼吸暂停综合征、阻塞性睡眠呼吸暂停综合征、睡眠相关的低通气/低氧综合征及其他睡眠相关呼吸疾病,其中第3类疾病由于会引起夜间持续低氧,将不可避免的导致肺动脉高压.     

骨生成蛋白及其受体信号途径和肺动脉高压

肺动脉高压主要与血管效应器失调、相关疾病及遗传因素有关。近年来研究发现,在所有的家族性肺动脉高压患者和40％的特发性肺动脉高压患者中,骨形成蛋白受体Ⅱ基因发生突变。本文对骨形成蛋白及其受体途径与特发性肺动脉高压的关系作一综述。     

应用彩色多普勒超声心动图评价终末期肾病患者肺动脉压力变化

目的 探讨应用彩色多普勒超声心动图评价终末期肾病( ESRD)及长期接受通过动-静脉通路进行血液透析的ESRD患者肺动脉高压的临床价值.方法 ESRD患者接受通过动-静脉通路进行血液透析组66例,ESRD患者无透析组42例,应用连续多普勒测量收缩期三尖瓣反流速度,并由峰速推算出收缩期三尖瓣口的跨瓣压差,进而推算出右室收缩压及肺动脉压力.透析组患者在完成透析后1h内进行超声心动图检查.结果 ESRD长期血液透析组肺动脉高压发病率、平均肺动脉压及心输出量明显增加,两组间肺动脉压及肺动脉高压发病率有显著性差异(P＜0.05).结论 彩色多普勒超声心动图能客观、无刨评价ESRD患者及经动-静脉内瘘血管通路进行血液透析的ESRD患者肺动脉压力,早期诊断ESRD相关肺动脉高压,有助于临床早期干预ESRD相关肺动脉高压,并改善预后.     

肺动脉高压联合药物治疗的研究进展

肺动脉高压是一类以肺血管阻力进行性增高为主要特征,最终导致右心衰竭、功能严重受限、死亡的疾病。近年来肺动脉高压在单一药物治疗上取得一定疗效,而联合应用不同的药物取得最佳临床疗效是治疗肺动脉高压的新观点,可以发挥药物间的协同效应,降低单个药物的不良反应。现综述联合药物治疗肺动脉高压的临床应用进展。     

Clinical perspectives of intravascular ultrasound

The history of intravascular ultrasound imaging, recent developments in catheter technology, and the initial in vivo experience are reviewed. Additionally, the article also discusses the potential applications of intravascular ultrasound imaging in coronary and peripheral arterial atherosclerosis, hypertension, pulmonary arterial disorders, valvular heart disease, aortic abnormalities, and in congenital heart disorders. Possible future directions are outlined.     

History of heart failure (including hypertension)

The article shortly summarizes without being complete the most important developments on heart failure and arterial hypertension in Germany from the 18th century until about 1990. During this time it is shown that important contributions from Germany added substantial knowledge to all internationally relevant advances in the field.     

Molecular and cellular mechanisms regulating vascular function and structure--implications in the pathogenesis of hypertension

Human essential hypertension is a complex, multifactorial, quantitative trait under polygenic control. The fundamental hemodynamic abnormality in hypertension is increased peripheral resistance due primarily to changes in vascular structure and function. These changes include arterial wall thickening and abnormal vascular tone, and are due to alterations in the biology of the cellular and noncellular components of the arterial wall. Multiple interacting humoral and mechanical factors as well as oxidative stress stimulate complex signalling pathways, which modulate vascular smooth muscle cell contraction and growth. Under normal physiological conditions, these finely regulated processes maintain vessel wall integrity and prevent pathological increases in blood pressure. However, under abnormal conditions, increased humoral and mechanical signalling results in vascular wall thickening and increased vascular tone, which play an important role in the pathogenesis and maintenance of hypertension. The present review discusses recent developments in the understanding of cellular and molecular mechanisms underlying vascular regulation in hypertension.     

Treatment of pulmonary arterial hypertension due to scleroderma: challenges for the future

Although progress has been made in treatment of pulmonary arterial hypertension, serious challenges remain. This article provides an overview of the challenges faced in treatment of PAH caused by scleroderma. It also provides a glimpse into the future, based on recent developments in the field that hold promise for enhancing the treatment of this disease.     

Lesions of target organs in arterial hypertension

A total of 530 patients with a variety of hypertensive conditions, including 476 patients with labile and stable essential hypertension, 40 with hypertensive chronic diffuse glomerulonephritis and hypertensive chronic pyelonephritis, and 14 with vasorenal hypertension, were investigated. Structure and function of target organs (the heart and the kidneys) were assessed by means of echocardiography (530) and intravital morphologic studies of renal biopsy specimens (89). A heterogeneous nature of hypertrophic developments associated with essential hypertension was demonstrated, with adequate, inadequate, disproportionate and excessive hypertrophy identified, while no correlation could be found between the kind of hypertension and the degree and nature of hypertrophy. Renal morphologic changes were also shown to be heterogeneous in labile and stable arterial hypertension, and early involvement of the renal mechanism presenting as structural changes was found to be possible.     

Autosomal-rezessive polyzystische Nierenerkrankung

Cystic kidney diseases are among the most important causes of end stage renal disease in children and adults. While the frequent autosomal dominant polycystic kidney disease (ADPKD) typically becomes clinically important in adulthood, the rare autosomal recessive polycystic kidney disease (ARPKD) is a severe disorder usually of early childhood. ARPKD is caused by mutations in the PKHD1 gene encoding the ciliary protein fibrocystin and is characterized by massively enlarged bilateral reniform and cystic kidneys. Liver involvement as congenital hepatic fibrosis is obligatory and may lead to portal hypertension. Furthermore, arterial hypertension that may sometimes be severe and pronounced pulmonary hypoplasia are frequent findings. Overall there is great clinical variability. Just like other genetic cystic kidney diseases ARPKD is considered to be a ciliopathy and thus a systemic disorder. The cellular and molecular pathophysiological mechanisms remain poorly understood. Currently there are therefore no accepted causative or evidence-based treatment approaches. In addition to the symptomatic treatment of chronic kidney disease and arterial hypertension, therapy of portal hypertension is highly relevant. Kidney, liver or combined liver and kidney transplantation may be necessary. Despite massive progress in neonatal intensive care, pulmonary hypoplasia frequently remains a major therapeutic challenge. In this article we describe the clinical course, therapeutic options and recent developments in the field of ARPKD.     

Indications and outcomes in adult lung transplantation

Lung transplantation (LTx) is a treatment option for end-stage lung disease that would be otherwise fatal for specific patient populations. The most common indications for LTx in adults remain to be chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and idiopathic pulmonary arterial hypertension. Recent trends include performing re-transplantation while more patients over the age of 65 years are undergoing LTx. Even with these tendencies, slight improvements in survival have occurred. This article briefly reviews recent developments in adults undergoing LTx.     

Treatment of pulmonary hypertension: bench to bedside

Pulmonary arterial hypertension is an orphan disease and a model for drug developments over recent years. Expert centers have focused basic science on the pulmonary vasculature and the right ventricle, followed by a direct transfer of innovative concepts to clinical research. Successful examples for translational experimentation are the endothelin receptor antagonists, prostacyclin receptor agonists, and the activators of soluble guanylate cyclase. On the other hand, there have been failures such as vasoactive intestinal peptide, statins, and escitalopram. Several new drugs and gene therapy are under investigation, thus significant advances are anticipated.     

Genetics of pulmonary arterial hypertension: current and future implications

Idiopathic pulmonary arterial hypertension (formerly primary pulmonary hypertension) can affect more than one member of the same family. In the past 25 years scientists have exposed the inheritance pattern and a major element of the molecular basis for inherited pulmonary arterial hypertension. Familial pulmonary arterial hypertension is inherited as an autosomal dominant trait with incomplete penetrance (i.e., several individuals inherit a predisposition to the disease, but never express it). Mutations in the gene that codes for bone morphogenetic protein receptor type II (BMPR-II) are a major predisposition for the development of pulmonary arterial hypertension. These mutations are present in at least half of familial cases of pulmonary arterial hypertension and 10 to 25% of idiopathic pulmonary arterial hypertension patients. Mutations in the gene that codes for activin receptor-like kinase (ALK 1), another transforming growth factor beta (TGF-beta) cell surface receptor, appear responsible for the rare occurrence of pulmonary arterial hypertension in patients with hereditary hemorrhagic telangiectasia. These discoveries coupled with other basic investigations offer opportunities for advances in the management of pulmonary arterial hypertension.