一氧化氮与先天性心脏病合并肺动脉高压

一氧化氮是一种脂溶性气体,它具有独特的理化性质和生物学活性,主要由血管内皮产生,在先天性心脏病合并肺动脉高压的发生、发展过程中起到了重要作用。吸入一氧化氮气体,可选择性扩张肺血管,降低肺动脉阻力和肺动脉压。现主要综述一氧化氮与先天性心脏病合并肺动脉高压的相互作用关系及一氧化氮在治疗上的研究进展。     

急性肺血管药物扩张试验在评价先天性心脏病合并重度肺动脉高压中的应用进展

<正>一、先天性心脏病合并重度肺动脉高压继发于左向右分流型先天性心脏病(CHD)的肺动脉高压(PAH)是一种进行性病变,主要表现为肺动脉压力和肺血管阻力的进行性升高,最终导致右心衰竭甚至死亡。这类肺动脉高压按其性质可分为动力性肺动脉高压和梗阻性肺动脉高压,CHD合     

先天性体肺分流心脏病合并肺动脉高压患者的手术适应证评估进展

先天性体肺分流性心脏病可导致肺循环持续的血流量增加、肺血管收缩和肺血管重构,引起肺动脉压力升高,影响手术治疗的效果。在肺血管病变尚可逆时,手术后患者肺动脉压力下降,预后良好;当肺血管病变严重,手术后肺动脉压力持续升高,预后不良。如何准确判断先天性心脏病合并肺动脉高压患者的手术适应证仍有争议,国内外临床医生和基础研究学者都对先天性体肺分流心脏病合并肺动脉高压患者的手术适应证评估进行了深入研究,对此进行总结综述。     

ACEI在左向右分流先天性心脏病肺动脉高压中的应用

小儿肺动脉高压 (PH)以左向右分流先天性心脏病所致的 PH最为多见 ,它可发生于小儿先天性心脏病演变过程中的各个阶段 ,也常常是不少先心病手术时间和方式选择以及导致死亡的重要因素。受到血管扩张剂治疗顽固性左心衰竭的启发 ,从1 951年起 [1] ,许多学者开始使用扩血管药物治疗PH,希望能通过扩张肺小动脉 ,达到降低肺动脉压力、肺血管阻力及右室后负荷的目的 ,从而改善临床症状。近年来 ,虽然许多学者在用扩血管药物治疗肺动脉高压方面作了大量的研究 ,仍有一些重要问题有待解决 ,如哪些肺动脉高压病人用扩血管药物治疗最可能有效 ?哪…     

血管内超声评价先天性心脏病合并肺动脉高压肺血管病理变化的初步探讨

目的 :探索血管内超声在合并肺动脉高压的先天性心脏病 (先心病 )患儿肺动脉内检查的可行性并评价肺血管病理变化。　　方法 :对 6例合并肺动脉高压的先心病患儿进行肺动脉血管内超声检查 ,观测其管腔大小、内膜和中层的厚度以及血管的搏动性 ,同时与右心导管血液动力学在吸氧前后的变化结果进行了比较。　　结果 :肺动脉内超声能够清晰观测到其管壁的三层组织学变化 ,中层增厚 ,吸氧后肺动脉搏动性明显增强 ,与右心导管血液动力学检查结果有高度相关性。　　结论 :血管内超声对肺动脉的检查安全可靠 ,检查结果能够较好的反映肺动脉形态学变化。     

先天性心脏病合并肺动脉高压患者血清血管紧张素转化酶2活性变化的研究

目的观察先天性心脏病（CHD）伴肺动脉高压（PAH）患者血管紧张素转化酶2（ACE2）活性水平的变化,探讨其与肺动脉高压的关系。方法先天性心脏病患者68例,分为先天性心脏病肺动脉压力正常组36例、先天性心脏病合并轻中度肺动脉高压组19例和先天性心脏病合并重度肺动脉高压组13例。抽取受试者静脉血,应用比色法检测ACE2酶活性水平。结果先心病重度肺动脉高压组血清ACE2酶活性较先心病肺动脉压力正常组明显降低（1．28±0．40比1．92±0．64,P〈0．05）,血清ACE2酶活性与肺动脉压力存在低度负相关关系（r=-0．367,P〈O．01）。结论ACE2酶活性降低可能在先天性心脏病肺动脉高压的发生、发展中起着重要的作用。     

靶向药物联合缺损修复治疗成人先天性心脏病相关肺动脉高压的预后研究

目的:分析靶向药物联合缺损修复(Treat-Repair策略)治疗成人先天性心脏病合并肺动脉高压患者的有效及安全性.方法:回顾分析2010年12月至2019年9月,于我中心接受缺损修复的54例,平均年龄(31.07±10.09)岁的成人左向右分流先天性心脏病合并肺动脉高压[平均肺动脉压力(mPAP)≥25 mmHg,1...     

靶向药物对成人先天性心脏病合并重度肺动脉高压手术治疗的影响

目的：分析靶向药物对成人先天性心脏病合并重度肺动脉高压手术治疗的影响，探讨药物干预下的手术指征及围手术期处理要点。方法：自2015年1月至2017年6月，我科共完成46例成人先天性心脏病合并重度肺动脉高压患者的外科矫治手术。术前予以3～24个月的靶向药物治疗，术后继续应用靶向药物治疗。结果：①术前经过一段时间的靶向药物治疗，患者经皮氧饱和度、动脉血氧分压、6分钟步行试验距离、双向分流、左室射血分数、肺动脉平均压、肺血管阻力、肺循环血量/体循环血量等指标明显改善。②术后24小时动脉血氧分压较术前明显升高，肺动脉平均压较术前明显下降。围手术期出现肺动脉高压危象10例，再次气管插管3例，脑梗死1例；死亡1例，原因为肺动脉高压危象致循环衰竭。多因素Logistic regression分析提示肺血管阻力≥8wood，肺循环血量/体循环血量≤1.25是围手术期肺动脉高压危象的独立危险因素。1例失访，44例随访6个月～3年，无远期死亡及缺损残余漏，患者经皮氧饱和度、6分钟步行试验距离较术前明显改善，超声心动图提示仍有2例患者肺动脉收缩压高于正常值。结论：成人先天性心脏病合并重度肺动脉高压患者，经过一定时间的靶向药物治疗，当肺血管阻力＜8wood，肺循环血量/体循环血量＞1.25时，可以接受外科手术矫治。术后继续应用靶向药物治疗，预防并及时处理肺动脉高压危象是围手术期处理的关键。     

先天性心脏病相关性肺动脉高压的诊治现状和挑战

在过去的20年,由于小儿心脏外科和先天性心脏病介入治疗技术的发展,使得先天性心脏病患者的预后较过去明显改善,先天性心脏病合并艾森曼格综合征的比例由过去的8%下降至4%。然而,先天性心脏病相关性肺动脉高压仍是该领域面临的最大挑战,尤其是艾森曼格综合征。先天性心脏病相关性肺动脉高压是影响先天性心脏病患者生活质量和生存率重要的因素之一。现就目前先天性心脏病相关性肺动脉高压的诊治现状和挑战做一综述。     

内皮细胞凋亡与肺动脉高压

随着肺动脉高压研究的不断深入,肺血管内皮细胞凋亡在肺动脉高压形成过程中的重要作用被逐步认识。多种疾病和环境因素导致肺血管内皮损伤、内皮细胞凋亡增加、功能障碍,从而促进肺动脉平滑肌细胞和成纤维细胞增殖、肺动脉重构和血栓形成;肺血管内皮细胞凋亡还诱导产生凋亡抵抗表型的内皮细胞过度增殖,形成丛样病变和肺血管闭塞,最终导致严重肺动脉高压。因而在肺动脉高压发生发展的不同时期,调控肺血管内皮细胞凋亡可能是预防和治疗肺动脉高压的一种新策略。     

先天性心脏病并发肺动脉高压肺血管重建的研究进展

详尽论述了先心病并发肺动脉高压的肺血管重建发生机制及研究进展,以及一氧化氮、内皮素及内皮素受体、心血管调节肽及血管内皮生长因子四种血管活性物质在肺血管重建中的作用。     

Cerebrovascular disease associated with sickle cell pulmonary hypertension

In patients with sickle cell disease, anemia is a recognized risk factor for stroke, death, and the development of pulmonary hypertension. We have proposed that hemolytic anemia results in endothelial dysfunction and vascular instability and can ultimately lead to a proliferative vasculopathy leading to pulmonary hypertension. Consistent with this mechanism of disease, we now report a case series of six patients with obliterative central nervous system vasculopathy who also have pulmonary hypertension and high hemolytic rate. These patients, identified in the course of a prospective screening study for pulmonary hypertension, presented with neurological symptoms prompting neuroimaging studies. Compared to 164 other patients of similar age in the screened population, those with newly diagnosed or clinically active cerebrovascular disease have significantly lower hemoglobin levels and higher levels of lactate dehydrogenase. A review of the literature suggests that many clinical, epidemiological, and physiological features of the arteriopathy of pulmonary hypertension closely overlap with those of stroke in sickle cell disease, both known to involve proliferative vascular intimal and smooth muscle hypertrophy and thrombosis. These cases suggest that cerebrovascular disease and pulmonary hypertension in sickle cell disease share common mechanisms, in particular, reduced nitric oxide bioactivity associated with particularly high-grade hemolysis. Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension.     

肺血管内皮细胞功能障碍与肺动脉高压

肺动脉高压的发病机制是一个复杂的、多因素参与的过程.近年来,逐步形成内皮功能紊乱学说,认为肺血管内皮是引起血管收缩和特征性病理改变的首要因素.本文就肺血管内皮细胞功能障碍和肺动脉高压的研究进展作一综述.     

血管内皮生长因子与慢性阻塞性肺疾病继发肺动脉高压的关系

血管内皮生长因子(vascular endothelial growth factor,VEGF)是一种重要的血管内皮细胞丝裂原和通透因子.肺血管的重塑与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)继发肺动脉高压密切相关.VEGF贯穿于COPD发展的全过程,在COPD的不同时期呈现不同的表达水平,发挥不同的生物学作用.气道炎症、低氧等因素可以在COPD早期促进VEGF及其受体的表达上调从而导致肺血管重塑的发生发展,VEGF也可以对COPD后期继发肺动脉高压时的重度肺血管重塑起到一定的修复作用.通过阐述VEGF、COPD肺血管重塑及继发肺动脉高压之间的相互关系,可以对COPD继发肺动脉高压的诊断和治疗提供新的思路.     

Pulmonary hypertension: a cellular basis for understanding the pathophysiology and treatment

Much of the understanding of hypertensive pulmonary vascular disease comes from studies of primary pulmonary hypertension. The three subtypes of primary pulmonary hypertension, plexogenic pulmonary arteriopathy, thromboembolic pulmonary hypertension and venoocclusive disease, have served as a basis to understand the mechanisms and to develop treatments of all forms of pulmonary hypertension. However, many inconsistencies regarding presumed pulmonary vasoconstriction and recurrent embolization remain. With newer data on the influence of the endothelium on vascular responsiveness and thrombosis, it appears that older concepts regarding the pathophysiology of pulmonary hypertension need to be revised. Recent studies have shown that plexogenic pulmonary arteriopathy is associated with abnormalities of endothelial structure and function that could result in impaired release of endothelial derived relaxing factors. Thromboembolic pulmonary arteriopathy, or more properly thrombotic pulmonary hypertension, appears to be the result of endothelial cell injury that creates a procoagulant environment in the pulmonary vascular bed with the development of widespread eccentric intimal proliferation and thrombosis in situ. It is possible that the effectiveness of vasodilator or anticoagulant therapy depends on the nature of the endothelial injury. Secondary pulmonary hypertension without endothelial injury, such as that which occurs with hypoxic lung disease or mitral stenosis, appears more satisfactorily treated when the primary cause is reversed.     

Impact of pulmonary vascular resistances in heart transplantation for congenital heart disease

Congenital heart disease is one of the major diagnoses in pediatric heart transplantation recipients of all age groups. Assessment of pulmonary vascular resistance in these patients prior to transplantation is crucial to determine their candidacy, however, it is frequently inaccurate because of their abnormal anatomy and physiology. This problem places them at significant risk for pulmonary hypertension and right ventricular failure post transplantation. The pathophysiology of pulmonary vascular disease in children with congenital heart disease depends on their pulmonary blood flow patterns, systemic ventricle function, as well as semilunar valves and atrioventricular valves structure and function. In our review we analyze the pathophysiology of pulmonary vascular disease in children with congenital heart disease and end-stage heart failure, and outline the state of the art pre-transplantation medical and surgical management to achieve reverse remodeling of the pulmonary vasculature by using pulmonary vasodilators and mechanical circulatory support.     

Reversible pulmonary hypertension, tricuspid regurgitation and right-sided heart failure associated with hyperthyroidism: case report and review of the literature

Primary pulmonary hypertension carries a grim prognosis, therefore, it is imperative that prior to reaching this diagnosis, a thorough search be made for all possible causes of pulmonary hypertension. An uncommon cause of pulmonary hypertension amenable to treatment may occasionally be identified. This case report describes a young woman who presented with rapidly progressive right heart failure. Work up for the common secondary causes of pulmonary hypertension was negative, including, congenital intracardiac shunts, left-sided atrial or ventricular heart disease, left-sided valvular heart disease, disorders of the respiratory system including hypoxemia and pulmonary thromboembolic and venoocclusive disease, collagen vascular disease, portal hypertension, HIV infection as well as pulmonary hypertension secondary to drugs and toxins. The only concurrent illness identified was Graves disease. After treatment of hyperthyroidism there was complete resolution of the right heart failure, tricuspid regurgitation, and the pulmonary hypertension. Only a few cases of reversible pulmonary hypertension and right heart failure associated with hyperthyroidism have been reported worldwide. In these patients, the most striking feature has been the normalization of the cardiovascular findings after adequate treatment of hyperthyroidism. The exact reasons for the development of pulmonary hypertension in hyperthyroidism are unclear. Proposed mechanisms include high cardiac output-induced endothelial injury, increased metabolism of intrinsic pulmonary vasodilating substances resulting in elevated pulmonary vascular resistance, and autoimmune phenomenon. Hyperthyroidism should be included in the causes of secondary pulmonary hypertension and/or otherwise unexplained right heart failure. This is especially important because hyperthyroidism is a treatable entity and its cardiac manifestations may be completely reversible.     

Persistent pulmonary hypertension of the newborn associated with pulmonary atresia and intact interventricular septum

Neonates with pulmonary atresia and intact interventricular septum (PAIVS) do not have pulmonary vascular disease secondary to their heart abnormality. Persistent pulmonary hypertension of the newborn has not been described in association with this condition. The case is reported of a female neonate born with PAIVS, who preoperatively had no clinical evidence or any risk factors for persistent pulmonary hypertension of the newborn, but whose postoperative course was highly suggestive of persistent pulmonary hypertension; necropsy confirmed the features of pulmonary vascular disease.


Keywords: persistent pulmonary hypertension; pulmonary atresia and intact ventricular septum; pulmonary vascular disease; surgery; congenital heart defects     

The pathobiology of pulmonary hypertension. Endothelium

Dysfunctional endothelial cells have a central and critical role in the initiation and progression of severe pulmonary hypertension. The elucidation of the mechanisms involved in the control of endothelial cell proliferation and cell death in the pulmonary vasculature, therefore, is fundamentally important in the pathogenesis of severe pulmonary hypertension and of great interest for a better understanding of endothelial cell biology. Because the intravascular growth of endothelial cells resulting in tumorlets is unique to severe pulmonary hypertension, this phenomenon can teach researchers about the factors involved in the formation and maintenance of the normal endothelial cell monolayer. Clearly, in severe pulmonary hypertension, the "law of the endothelial cell monolayer" has been broken. The ultimate level of such a control is at the altered gene expression pattern that is conducive to endothelial cell growth and disruption of pulmonary blood flow. Secondary pulmonary hypertension certainly also is associated with proliferated pulmonary endothelial cells and plexiform lesions that are histologically indistinguishable from those in PPH. What is then the difference in the mechanisms of endothelial cell proliferation between primary and secondary pulmonary hypertension? The authors believe that PPH is a disease caused by somatic mutations in key angiogenesis- or apoptosis-related genes such as the TGF-beta receptor-2 and Bax. The loss of these important cell growth control mechanisms allows for the clonal expansion of endothelial cells from a single cell that has acquired a selective growth advantage. On the other hand, the proliferated endothelial cells in secondary pulmonary hypertension are polyclonal. It follows from this finding that local (vascular) factor(s) (such as increased shear stress), rather than mutations, play a major role in triggering endothelial cell proliferation. In PPH and secondary pulmonary hypertension, the researcher can postulate that the pulmonary vascular bed contains progenitor-like cells with the capacity of dysregulated growth. The main difference in the pathogenesis of primary and secondary pulmonary endothelial cell proliferation therefore may be the initial mechanism involved in the recruitment of an endothelial progenitor-like cell. In PPH, anorexigen-associated, and familial PPH, the proliferation of endothelial cells occurs from a mutated single cell, whereas in secondary pulmonary hypertension, several progenitor-like cells would be activated to grow. The abnormal endothelial cells in both forms of severe pulmonary hypertension expand because of the expression of angiogenesis-related molecules such as VEGF, VEGFR-2, HIF-1 alpha, and HIF-beta. Also important for the expansion of these cells is the down-regulation of expression of apoptosis-related mediators such as TGF-beta receptor-2 or Bax. The success of any therapy for severe pulmonary hypertension requires that the underlying process of endothelial cell proliferation could be controlled or reversed.     

内皮祖细胞在肺动脉高压的作用

内皮祖细胞是成熟血管内皮细胞的前体细胞,属于干细胞群体,其在血管再生与修复方面的应用越来越受到关注.肺动脉高压作为一种致死性很高的肺血管疾病,其发病与血管内皮损伤密切相关.目前的研究证实,内皮祖细胞在肺动脉高压血管内皮修复中具有重要作用,内皮祖细胞移植有可能成为临床治疗肺动脉高压的一种有效手段.