卡托普利和氯沙坦对肺动脉高压大鼠肺动脉零应力状态的影响

目的通过观察肺动脉高压大鼠肺动脉张开角的大小,了解卡托普利及氯沙坦对肺动脉高压大鼠肺动脉零应力状态的影响。方法选取健康雄性SD大鼠（体重为350g-400g）40只,随机分为试验组（n=30）和对照组（n=10）。试验组大鼠按参照文献行左肺切除,术后第7天于项背部皮下注射野百合碱（monocrotaline,MCT）（Signa公司,美国）,剂量为60mg／kg,建立肺动脉高压（pulmonary artery hypertension,PAH）模型。于手术后第5周（注射野百合碱后第4周）,行血流动力学检查后处死。随机从试验组中取20只大鼠,从左肺切除术前3d起,分别给予卡托普利10mg／（kg·d）（captopril组,n=10）,氯沙坦15mg／（kg·d）（losartan组,n=10）,另外10只喂等量生理盐水（PM组,n=10）,口服给药直至处死前2d。对照组不做任何处理。5周后观察4组的平均肺动脉压（mean pulmonary arterial pressure,mPAP）、右心室质量,即右心室／左心室＋室间隔[RV／（LV＋S）],通过应用计算机图像分析软件测量肺动脉张开角的方法测定大鼠肺动脉的零压力状态。结果PM组平均肺动脉压为（39．62±1．46）mmHg、右心室质量（比值）为（62．66±0．61）％,分别较captoprit组[（24．38±1．19）mmHg,（48．82±1．12）％],losartan组[（23．95±0．97）mmHg,（49．15±1．41）％]及对照组[（17．62±1．12）mmHg,（26．86±0．96）％]增高,差异有显著意义（P〈0．001）;captopril组和losartan组比较,差异无显著意义（P〉0．05）。PM组肺动脉张开角[（79．13±4．19）。]明显小于captopril组[（103．63±5．69）°]、losartan组[（102．91±5．77）°]及对照组[（139．17±4．27）°],差异有显著意义（P〈0．001）;而captopril组和losartan组比较,差异无显著意义（P〉0．05）。结论卡托普利及氯沙坦通过干预肺动脉零应力状态,从而缓解肺动脉高压和肺血管重构的形成。     

低氧性肺动脉高压肺血管重构中的细胞因子调控

低氧性肺动脉高压(HPH)是以低氧性肺动脉收缩和低氧性肺血管重构引起的肺动脉压持续升高为特征的临床常见病症。细胞增殖与凋亡是肺血管重构中极其重要的一个环节,低氧诱导分子-Ⅰ、一氧化氮、一氧化碳、K+通道及5-羟色胺均参与并影响肺动脉平滑肌细胞的增殖及凋亡。本文就上述致低氧性肺动脉高压因素在肺血管重构中的机制及作用作一综述,为低氧性肺动脉高压的分子水平干预和早期康复措施介入提供新的靶点。     

支气管肺发育不良及肺动脉高压有关信号通路研究现状

支气管肺发育不良(BPD)是早产儿的主要并发症之一。中至重度BPD患儿中,约25%可能并发BPD相关肺动脉高压(PH),是影响BPD患儿病死率增高及后期生存质量降低的主要原因。目前针对上述BPD及其相关PH的预防与治疗方法尚有限,因此深入研究其发病机制,进而进行针对性有效治疗刻不容缓。近年研究发现,在BPD及其相关PH发生、发展过程中,许多相关信号通路存在异常,如血管生成素(Ang)、血管内皮生长因子(VEGF)、转化生长因子(TGF)-β、Wnt、结缔组织生长因子(CTGF)、成纤维细胞生长因子(FGF)10、微小RNA(miRNA)、小窝蛋白(Cav)-1信号通路等,这些加深了临床对BPD及其相关PH发病机制的理解,并为其治疗提供了新思路。笔者拟就BPD及其相关PH所涉及相关信号通路研究现状进行阐述。     

缺氧性肺动脉高压大鼠肺组织面积密度变化及其机制的研究

目的　研究缺氧性肺动脉高压 (HPH)肺组织面积密度变化及其机制。方法　模拟海拔5km高原连续缺氧 ,制备HPH大鼠动物模型 ,用图像分析、光镜、电镜、组织化学等方法分析、观察缺氧后 10、2 0、30d和平原对照组肺组织面积密度及形态学变化。结果　缺氧后大鼠肺组织面积密度明显增加 ,以 2 0d和 30d为著 ,缺氧 10d时为 2 7.0 8%± 1.2 9%、2 0d时为 31.33%± 0 .72 %、30d时为31.10 %± 1.95 % ,与对照组 ( 2 2 .78%± 1.17% )比较 ,差异均有显著性 (P <0 .0 5 ,P <0 .0 1)。缺氧 2 0d时与 10d比较 ,差异有显著性 (P <0 .0 5 ) ,缺氧 30d与 10d比较 ,差异无显著性 ,但其P值 ( 0 .0 5 7)接近显著性水平。大鼠Ⅱ型肺泡上皮细胞 (PⅡ )不同程度肿胀、退变 ,板层体减少或空化 ;肺泡腔表面活性物质 (PS)呈泡沫状。各级小动脉管壁增厚 ;毛细血管内中性粒细胞滞留、嵌塞 ,血小板聚集 ;内皮细胞肿胀 ,基底膜增厚。结论　缺氧可引起大鼠肺组织面积密度增加 ,肺泡有效气体交换面积减少。其变化与PⅡ和PS系统受损所致的肺萎陷、肺血管结构重塑、肺泡腔有形成分增加有关     

先天性心脏病伴重度肺动脉高压术后肺高压危象的监控与预防

目的探讨先天性心脏病（先心病）伴肺动脉高压术后肺高压危象的监控及预防。方法回顾性分析1995—2006年监护治疗的113例先心病伴重度肺高压和51例先心病伴中度肺高压病人中术后肺高压危象的发生率，分析肺高压危象与术时肺高压程度、术后肺动脉压下降程度、手术的年龄及术后预防措施的关系。结果113例重度肺高压病人中发生肺动脉高压危象18例（15．9％）；51例中度肺高压患者中无肺高压危象发生。术毕Pp/Ps〈0．5者肺高压危象发生率为7．2％，Pp／Ps≥0．5者肺高压危象发生率为40．0％。术时年龄1-3岁组术后易发生肺高压危象。〈1岁组发生率5．4％，1-3岁组发生率为25．9％，≥3岁组发生率为5．6％。采取系列预防措施后发生率由22．4％下降至6．5％。结论对有发生肺高压危象倾向者，采取严密的监控及个体化施药。早期治疗是预防术后肺高压危象的重要措施。     

Notch信号传导通路和滋养细胞侵袭

Notch受体是进化上高度保守的跨膜受体蛋白家族,广泛存在于多个物种中.研究发现,Notch信号传导通路相关分子广泛存在于人体不同组织中,调节细胞的增殖、分化及凋亡等,参与恶性细胞的侵袭转移,并且和胚胎发育、血管发生及胎盘血管生理性改变等过程密切相关.综述关于Notch信号传导通路增强滋养细胞侵袭性,参与胎盘血管形成等...     

肺动脉高压

一个世纪前学者就可以测定人体肺动脉压力,肺动脉粥样硬化作为慢性肺动脉高压(pulmonry arterial hypertension,PAH)的形态学已被广泛接受.     

肺动脉高压

一个世纪前学者就可以测定人体肺动脉压力，肺动脉粥样硬化作为慢性肺动脉高压（pulmonry arterial hypertension，PAH）的形态学已被广泛接受。1891年德国医生Ernst von Romberg无法从尸检发现肺血管病变的病因学，因此，他将该病命名为“肺血管硬化”。1901年阿根廷Abel Ayerza教授叙述了慢性呼吸困难、紫绀、红细胞增多并伴有肺动脉硬化的综合征。     

肺动脉高压的护理体会

1充分镇静。2充分供氧,及时纠正低氧血症。3过度通气。PaCO2维持在正常偏低的水平(PaCO230~35mmHg左右),以利于降低肺血管阻力,必要时给予血管扩张剂。4吸入NO。5吸痰时尽量避免长时间的刺激,动作要轻柔,吸痰前后要吸纯氧5分钟~10分钟,避免加重缺氧。6术后适当延长辅助通气时间     

慢性阻塞性肺疾病合并肺动脉高压

目的 研究分析肺动脉高压形成的原因,分析慢性阻塞性肺疾病合并肺动脉高压患者的治疗方法与治疗效果.方法 经过对我院2010年1月~2011年12月所收治的80例慢性阻塞性肺疾病合并肺动脉高压患者进行对比性治疗.将80例患者分为两组,对照组与治疗组,平均每组40例.对照组采用常规治疗法治疗慢性阻塞性肺疾病,治疗组针对慢性阻塞性肺疾病采取规范化治疗.经过3周的治疗后分析两组患者的血气和肺动脉压.结论 经过对比性治疗得出,采用规范化治疗的治疗组其肺动脉压以及血气等情况的改善均比对照组显著.讨论慢性阻塞性肺疾病合并肺动脉高压患者经过规范化治疗,能有效降低患者的肺动脉高压,缓解病情的发展.     

The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Recent developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial–mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments. In this article, we provide new insight for diagnosing, preventing and treating PAH by adding to the current knowledge of the intestinal flora mechanisms and its metabolites efficacy involved in PAH.     

Prevalence of Micronutrient Deficiencies and Relationship with Clinical and Patient-Related Outcomes in Pulmonary Hypertension Types I and IV

Background: Pulmonary hypertension (PH) is a rare progressive and lethal disease affecting pulmonary arteries and heart function. The disease may compromise the nutritional status of the patient, which impairs their physical performance. This study aimed to determine the prevalence of micronutrient deficiencies in pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients. Methods: Eighty-one blood samples from a prospective observational cohort study were analyzed for concentrations of micronutrients and inflammation-related factors. The samples consisted of newly diagnosed (treatment-naive) PAH and CTEPH patients and patients treated for 1.5 years according to ERS/ESC guidelines. Results: In the newly diagnosed group, 42% of PAH patients and 21% of CTEPH patients were iron deficient compared to 29% of PAH patients and 20% of CTEPH patients in the treatment group. Vitamin D deficiency occurred in 42% of the newly diagnosed PAH patients, 71% of the newly diagnosed CTEPH patients, 68% of the treated PAH patients, and 70% of the treated CTEPH patients. Iron levels correlated with the 6 min walking distance (6MWD). Conclusions: Iron and vitamin D deficiencies are highly prevalent in PAH and CTEPH patients, underlining the need for monitoring their status. Studies evaluating the effects of supplementation strategies for iron and vitamin D are necessary.     

The initial 18 months of the first multi-disciplinary regional Pulmonary Arterial Hypertension Clinic in Australia

Objective: To report the initial 18 months experience of the first multi‐disciplinary regional Pulmonary Arterial Hypertension (PAH) Clinic in Australia. Design: Prospective cohort study. Setting: Community setting on the mid‐north coast of New South Wales. Participants: A total of 47 patients (mean age ± standard error of the mean: 71.8 ± 1.8 years; male/female ratio 13/34). Main outcome measures: Diagnosis of PAH, exclusion of other causes of pulmonary hypertension, commencement of PAH‐specific pharmacotherapy. Results: Twenty‐three (49%) patients were discharged back to their GP with pulmonary hypertension from a combination of ischaemic heart and/or lung disease. Three (6%) patients died from connective tissue disease (CTD)‐related PAH with one death (2%) from ischaemic heart disease. Five (11%) patients remain on treatment (n = 2, Bosentan for congenital heart disease‐related PAH; n = 1 Bosentan for CTD‐related PAH; and n = 1 Bosentan and n = 1 Sildenafil for primary PAH). Fifteen (32%) patients have ongoing review for PAH related to CTD (n = 11), carcinoid (n = 1) and uncertain cause (n = 3). Conclusion: Patients with CTD‐related PAH have a poor prognosis. PAH should be considered in anyone with dyspnoea without obvious features of cardiac or pulmonary disease, especially in the setting of a CTD. Regional population centres are under‐resourced with PAH specialty medical services. We have sought to address this by establishment of the first regional multi‐disciplinary PAH Clinic in Australia.     

米力农治疗新生儿持续肺动脉高压临床观察

目的探讨米力农对新生儿持续肺动脉高压（PPHN）的治疗效果。方法 35例确诊新生儿持续肺动脉高压的患儿应用米力农以0.5μg·kg-1·min-1速度持续静脉滴注在治疗中根据血压变化适当增加或减少米力农输入速度,连用3天,于治疗前、治疗后动态监测患儿血压、肺动脉收缩压（PASP）、经皮氧饱和度（SpO2）及动脉PaO2等变化。结果应用米力农治疗后患儿临床症状明显改善,肺动脉收缩压明显下降,血氧饱和度、动脉氧分压明显升高,差异有显着性（P〈0.01）,35例接受米力农治疗的PPHN患儿治愈22例,好转8例,无效5例,有效率85.7%。结论米力农对新生儿持续肺动脉高压具有良好治疗效应,可有效降低肺动脉压力,改善临床症状。     

米力农治疗新生儿持续肺动脉高压临床观察

目的探讨米力农对新生儿持续肺动脉高压(PPHN)的治疗效果。方法 35例确诊新生儿持续肺动脉高压的患儿应用米力农以0.5μg·kg-1·min-1速度持续静脉滴注在治疗中根据血压变化适当增加或减少米力农输入速度,连用3天,于治疗前、治疗后动态监测患儿血压、肺动脉收缩压(PASP)、经皮氧饱和度(SpO2)及动脉PaO2等变化。结果应用米力农治疗后患儿临床症状明显改善,肺动脉收缩压明显下降,血氧饱和度、动脉氧分压明显升高,差异有显着性(P<0.01),35例接受米力农治疗的PPHN患儿治愈22例,好转8例,无效5例,有效率85.7%。结论米力农对新生儿持续肺动脉高压具有良好治疗效应,可有效降低肺动脉压力,改善临床症状。     

PGE1对COPD合并缺氧性肺动脉高压的疗效

目的探讨前列腺素E1(PGE1)治疗老年慢性阻塞性肺疾病(COPD)合并缺氧性肺动脉高压的疗效.方法 60例COPD合并缺氧性肺动脉高压老年患者随机分为治疗组和对照组,每组30例,治疗组在常规治疗的基础上加用PGE1 10μg静脉注射,1次/d,15d为1疗程;对照组仅用常规治疗.在治疗前后测量肺动脉平均压(MPAP),动脉血氧分压(PaO2)及动脉二氧化碳分压(PaCO2),全血比黏度(%),血浆比黏度(%),红细胞压积(%),血小板黏附率(%)和血沉(mm/h).结果治疗后MPAP和PaCO2较治疗前明显降低(P《0.01),PaO2较治疗前明显升高(P《0.01),血液流变学各项参数较治疗前有明显改善(P《0.01),与对照组相比均有非常显著性差异(P《0.01).结论 PGE1治疗老年COPD合并缺氧性肺动脉高压有良好疗效.     

The Cost-Effectiveness of Bosentan in the United Kingdom for Patients with Pulmonary Arterial Hypertension of WHO Functional Class III

Objectives:  To assess whether bosentan or no active intervention, in addition to palliative care, is the more cost-effective first-line treatment option for patients with idiopathic pulmonary arterial hypertension (iPAH) or PAH associated with connective tissue disease (PAH-CTD) of WHO functional classification (FC) III in the United Kingdom.
Methods:  A cost-utility model simulated the treatment of patients with PAH of FC III. Patients remained on the selected intervention until death or clinical deterioration to FC IV, which would trigger initiation of epoprostenol treatment. The initial first-line treatment choice was assumed to not affect survival, but to affect the time until clinical deterioration, with this assumption being relaxed in sensitivity analyses. The distribution of time to clinical deterioration was estimated from long-term clinical trial databases of bosentan and from published literature. Utility associated with FC was taken from published literature. Costs were sourced from published literature and from specialist PAH centers. The time horizon was that of patients' lifetimes, with costs and benefits discounted at 3.5% per annum.
Results:  In the base case, bosentan dominated no active intervention because of the longer time to clinical deterioration and therefore the reduced time, per patient, spent in FC IV, which was associated with high costs of epoprostenol and reduced utility. In sensitivity analyses, bosentan was estimated to be more cost-effective than no active intervention, provided that any survival benefit was not greater than 2 years for patients with iPAH and 1 year for those with PAH-CTD.
Conclusions:  Bosentan is likely to be a more cost-effective first-line therapy for patients with PAH FC III in the UK than no active intervention.     

先天性膈疝合并肺动脉高压的发病机制及其临床诊疗研究进展

先天性膈疝(CDH)是新生儿外科常见危重病.该病预后的主要决定因素是其合并的肺发育不良及肺动脉高压(PH)的严重程度.对该病的临床治疗效果,是衡量新生儿科综合治疗水平的一项重要的指标.本文聚焦目前对CDH合并PH的发病机制及其临床诊疗的研究进展,并综述如下.     

硫酸镁联合硝苯地平治疗新生儿持续性肺动脉高压临床观察

目的观察硫酸镁联合硝苯地平治疗新生儿持续肺动脉高压(PPHN)的临床效果。方法对收治并确诊的31例PPHN患儿在呼吸支持的基础上采用硫酸镁联合硝苯地平治疗,硫酸镁首剂为200mg/kg,30min内微量泵静脉注入,继之维持量20～50mg/(kg.h)持续微量泵静脉注入,维持4个小时后改用硝苯地平1mg/(kg.次)口服,6～8小时应用一次。治疗期间监测血压、经皮血氧饱和度、血气分析、血钙、血镁和肺动脉压。结果硫酸镁联合硝苯地平治疗后,血氧饱和度、血氧分压、pH值与用药前比较明显改善,肺动脉压下降,差异显著。结论硫酸镁联合硝苯地平治疗新生儿持续肺动脉高压疗效确切,适合基层医院使用。