慢性血栓栓塞性肺动脉高压病例——与子宫肌瘤相关?

目的:通过分析2例慢性血栓栓塞性肺动脉高压(chronic thromboembolic pulmonary hypertension, CTEPH)的女性病人的病例报告以及循证国内外研究结果,提高对罕见的与子宫肌瘤相关的CTEPH的认识,提高肺动脉高压的诊治水平.方法:病例报告及文献检索.结果:既往有子宫肌瘤的女性肺动脉高压患者,临床发现肺动脉血栓形成,诊断为CTEPH,CTEPH发病可能与子宫肌瘤相关.结论:慢性血栓栓塞性肺动脉高压和/或肺动脉高压可能是子宫肌瘤一种罕见的并发症.在临床实践中应考虑其可能性,尽早给予病人子宫肌瘤剔除术治疗及抗血栓治疗,提高治疗水平.     

ROCKI及TGF-β1慢性血栓栓塞性肺动脉高压大鼠肺小动脉的表达

目的:观察Rho激酶(ROCK I)及转化生长因子β1(TGF-β1)在慢性血栓栓塞性肺动脉高压大鼠肺小动脉表达的动态变化.方法:雄性Wistar大鼠64只,随机分为8组,每组8只:初始对照组、栓塞3 d组、1周组、2周组、4周组、8周组、12周组、终末对照组.采血制备血栓,颈静脉注入,2周后第2次栓塞,全程腹腔注射氨甲环酸.达实验设定日期后,测各组大鼠平均肺动脉压(mPAP)、肺动脉相对中膜厚度(PAMT)、管壁面/积管总面积(WA/TA)、右室肥厚指数(RVHI),原位杂交检测ROCK I mRNA表达,免疫组化检测TGF-B,蛋白表达.结果:栓塞4周组至12周组大鼠随时间延长mPAP明显增高(均P<0.01);PAMT、WA/TA在4周后随时间延长显著增高(4周组P<0.05,8周、12周组P<0.01);8周后RVHI较对照组明显增高(8周组P<0.05,12周组P<0.01);栓塞后ROCK I mRNA原位杂交染色强度随时间延长出现增高趋势(3 d组至2周组P<0.05,4周组至12周组P<0.01),TGF-β1蛋白免疫组化染色强度随时间延长出现增高趋势(1周组、2周组P<0.05,4周组至12周组P<0.01).相关分析表明,ROCK I mRNA及TGF-β1,蛋白与mPAP、RVHI及血管重构指标均呈正相关(均P<0.01);ROCK I mRNA与TGF-β1蛋白表达呈正相关(r=0.612,P<0.01).结论:ROCK I和TGF-β1均可能参与慢性血栓栓塞性肺动脉高压、肺血管重构的病理生理过程,此过程中Rho/Rho激酶信号通路可能是TGF-β1发挥生物学效应的重要途径之一.     

急性肺动脉血栓栓塞症的诊断及外科治疗

目的探讨急性肺动脉血栓栓塞症的快速诊断、手术治疗和围手术期处理方法。方法 15例急性肺动脉栓塞症患者均在全麻体外循环下行肺动脉血栓切除术。结果术后10 d动脉血氧分压、动脉血氧饱和度均显著高于术前（P〈0.05）;术后10 d心脏超声右室横径、主肺动脉宽度、三尖瓣反流压差和反流面积均明显缩小（P〈0.05）。全组无手术死亡、并发症,术后全部病例心功能完全恢复正常。结论术前及时明确诊断、严格掌握手术适应证和手术时机、手术彻底清除血栓是治疗急性肺动脉血栓栓塞症成功的关键。     

慢性肺动脉血栓栓塞动物模型的建立

背景：目前国内外接近人体生理学的慢性肺动脉血栓栓塞的动物模型较少见。 目的：采用自体血栓反复注射法建立慢性肺动脉血栓栓塞的动物模型。 方法：将家兔随机分为栓塞组和假栓塞组,栓塞组家兔肺动脉多次注入自体血栓,假栓塞组用生理盐水替代血栓。 结果与结论：栓塞组干预4周后解剖肺动脉并经病理检测可发现有血栓机化,肺动脉CT造影均可见局部肺动脉截断征,以及炎症、梗死、胸膜增厚等间接征象,肺动脉解剖及病理均可发现实验兔肺动脉血栓形成机化及慢性炎症改变。结果证实,采用兔自体血栓反复注射法可成功建立慢性肺血栓栓塞动物模型。     

ROCK I及TGF-β1在慢性血栓栓塞性肺动脉高压大鼠肺小动脉的表达

目的：观察Rho激酶（ROCK I）及转化生长因子β1（TGF—β1）在慢性血栓栓塞性肺动脉高压大鼠肺小动脉表达的动态变化。方法：雄性Wistar大鼠64只,随机分为8组,每组8只：初始对照组、栓塞3d组、1周组、2周组、4周组、8周组、12周组、终末对照组。采血制备血栓,颈静脉注入,2周后第2次栓塞,全程腹腔注射氨甲环酸。达实验设定日期后,测各组大鼠平均肺动脉压（mPAP）、肺动脉相对中膜厚度（PAMT）、管壁面积／管总面积（WA／TA）、右室肥厚指数（RVHI）,原位杂交检测ROCK I mRNA表达,免疫组化检测TGF—β1蛋白表达。结果：栓塞4周组至12周组大鼠随时间延长mPAP明显增高（均P〈0．01）;PAMT、WA／TA在4周后随时间延长显著增高（4周组P〈0．05,8周、12周组P〈0．01）;8周后RVHI较对照组明显增高（8周组P〈0．05,12周组P〈0．01）;栓塞后ROCK I mRNA原位杂交染色强度随时间延长出现增高趋势（3d组至2周组P〈0．05,4周组至12周组P〈0．01）,TGF—β1蛋白免疫组化染色强度随时间延长出现增高趋势（1周组、2周组P〈0．05,4周组至12周组P〈0．01）。相关分析表明,ROCK I mRNA及TGF—β1蛋白与mPAP、RVHI及血管重构指标均呈正相关（均P〈0．01）;ROCKImRNA与TGF—β1蛋白表达呈正相关（r=0．612,P〈0．01）。结论：ROCKI和TGF—β1均可能参与慢性血栓栓塞性肺动脉高压、肺血管重构的病理生理过程,此过程中Rho／Rho激酶信号通路可能是TGF—β1发挥生物学效应的重要途径之一。     

肺动脉栓塞和下肢深静脉血栓的放射性核素显像进展（文献综述）

肺动脉栓塞简称为肺栓塞（PE），其与下肢深静脉血栓（DVT）同属于血栓性疾病，是临床上一种致死率、致残率较高的常见病、多发病。美国每年估计约有60万新发患者，是第三位常见的心血管疾病，其发病率仅次于缺血性心脏病和高血压。每年约有10万人死亡，死亡率仅次于肿瘤和心肌梗死。急性肺动脉栓塞的症状和体征表现多样，缺乏特异性，临床上较难做到早发现和早治疗，有相当一部分PE病人发现时已为慢性，留下了慢性血栓栓塞性肺动脉高压等后遗症，从而延误了最佳治疗时机。     

ROCKⅠ及TGF-β1在慢性血栓栓塞性肺动脉高压大鼠肺小动脉的表达

目的：观察Rho激酶（ROCKⅠ）及转化生长因子β₁ (TGF-β₁)在慢性血栓栓塞性肺动脉高压大鼠肺小动脉表达的动态变化。方法: 雄性Wistar大鼠64只,随机分为8组,每组8只：初始对照组、栓塞3 d组、1周组、2周组、4周组、8周组、12周组、终末对照组。采血制备血栓,颈静脉注入,2周后第2次栓塞,全程腹腔注射氨甲环酸。达实验设定日期后,测各组大鼠平均肺动脉压（mPAP）、肺动脉相对中膜厚度（PAMT）、管壁面积/管总面积(WA/TA) 、右室肥厚指数（RVHI）,原位杂交检测ROCKⅠmRNA表达,免疫组化检测TGF-β1蛋白表达。结果: 栓塞4周组至12周组大鼠随时间延长mPAP明显增高（均P<0.01）;PAMT、WA/TA在4周后随时间延长显著增高（4周组P<0.05,8周、12周组P<0.01）;8周后RVHI较对照组明显增高(8周组P<0.05,12周组P<0.01);栓塞后ROCKⅠmRNA原位杂交染色强度随时间延长出现增高趋势（3 d组至2周组P<0.05,4周组至12周组P<0.01）, TGF-β₁蛋白免疫组化染色强度随时间延长出现增高趋势（1周组、2周组P<0.05,4周组至12周组P<0.01）。相关分析表明,ROCKⅠmRNA 及TGF-β₁蛋白与mPAP、RVHI及血管重构指标均呈正相关(均P<0.01);ROCKⅠmRNA与TGF-β₁蛋白表达呈正相关(r=0.612,P<0.01) 。结论: ROCKⅠ和TGF-β₁均可能参与慢性血栓栓塞性肺动脉高压、肺血管重构的病理生理过程,此过程中Rho/Rho激酶信号通路可能是TGF-β1发挥生物学效应的重要途径之一。     

慢性血栓栓塞性肺动脉高压患者血管平滑肌细胞中FoxO3a和MMP2表达升高

目的研究FoxO3a及MMP2在慢性血栓栓塞性肺动脉高压(CTEPH)中的表达和作用。方法收集CTEPH患者20例,选取5例清洁手术标本,原代培养得到患者肺动脉血管平滑肌细胞(VSMCs);利用供体肺动脉主干作为对照,原代培养得到正常肺动脉VSMCs。免疫组织化学染色及Western blot检测血管组织及VSMCs中FoxO3a和MMP2表达。结果疾病组FoxO3a的积分吸光度值(IA)为:3 269±338,显著高于对照组的420±46(P0.01);疾病组和对照组的MMP2的IA分别为4 936±521、1 799±139(P0.01);FoxO3a和MMP2在疾病组表达较对照组明显升高(P0.05)。结论 CTEPH患者肺血管中FoxO3a和MMP2高表达,这两种信号分子可能参与了CTEPH血管重塑的过程。     

病例1 右室扩张型心肌病 肺动脉栓塞症 肺动脉高压

患者女,60岁,因反复气促17天,双下肢浮肿7天于1992年4月18日入院.患者在入院前17天突然出现气促,经休息后无缓解,反而渐加重.休息状态下仍觉气促,稍动即加剧.夜间不能平卧,需半坐卧位才能入睡,但无伴咳嗽、咳痰、咯血、无胸痛、胸闷,在当地医院曾作ECG示:“窦速,心肌劳损”,予有关治疗(具体不详)气促无减轻.于1992年4月8日在我院急诊留观.留观期间一直反复气促,不能平卧,7天前出现双下肢浮肿,呈凹陷性,并渐向近端发展,致双侧大腿以下有凹陷性浮肿,面部亦渐出现浮肿,在急诊经过强心、利尿、血管扩张剂等处理,自觉气促较前减轻,夜间可间断平卧入睡,双下肢浮肿渐消退.留观期间(4月日)作超声心动图示 右房室增大,右室右外侧壁     

肺血栓栓塞症肺动脉造影诊断检查操作规程

肺动脉造影（pulmonary arteriography，PA）为PTE诊断的经典参比方法。其敏感性约98％，特异性95～98％。作为一种有创性检查技术，应严格掌握其适应证。     

人参皂苷Rg2对野百合碱诱导肺动脉高压模型大鼠的作用

目的 探讨人参皂苷Rg2(ginsenoside-Rg2)对野百合碱(monocrotaline,MCT) 诱导的肺动脉高压(pulmonary arterial hypertension,PAH) 模型大鼠的作用.方法 将48只雄性SD 大鼠随机分为对照组、模型组、人参皂苷Rg2 (20、40、80 mg/kg) 组和波生坦(Bos,200 mg /kg) 组,每组8只.一次性腹腔注射MCT(50 mg/kg) 复制PAH 模型,此后按分组灌胃给药,每天1 次,连续28d.通过颈总动脉和右心室用八道生理记录仪测定右心室收缩压(right ventricle systolic pressure,RVSP)、平均动脉压(mean arterial blood pressure,MBP)、心率(heart rate,HR).处死动物后采集血浆测定内皮素-1(endothelin-1,ET-1)和一氧化氮(nitric oxide,NO)的水平并测定右心肥大指数.结果 野百合碱注射后第28天时,与对照组比较,模型组右心室压力、右心肥大指数明显升高,心率和平均动脉压明显减小;血浆ET-1水平明显增加,NO水平明显降低.人参皂苷Rg2能明显缓解这些变化.结论 人参皂苷Rg2对野百合就所致的肺动脉高压模型大鼠具有改善作用.     

雷米普利通过调节细胞外调节激酶1/2的活性抑制肺动脉高压大鼠肺血管重构

目的探讨雷米普利抑制野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠肺血管重构是否与调节细胞外调节激酶1/2（ERK1/2）活性有关。方法雄性Sprague-Dawley大鼠30只,质量280～320g,随机分为：正常对照组、PAH组、PAH＋雷米普利组。PAH组和PAH＋雷米普利组一次性颈部注射MCT60mg/kg后,PAH＋雷米普利组用雷米普利灌胃,PAH组用生理盐水灌胃。对照组颈部注射生理盐水后,用生理盐水灌胃。4周后,测定大鼠的右室收缩压（RVSP）和右心室肥厚指数（RVHI）,并用图像分析软件,测定肺小动脉管壁厚度（WT）占动脉外径（ED）的百分比（WT,%）及管壁面积（WA）占血管总面积的百分比（WA,%）。放射免疫法检测肺组织中血管紧张素Ⅱ（AngⅡ）浓度。Western免疫印迹分析肺组织中ERK1/2磷酸化水平。结果PAH组的RVSP、RVHI、WT（%）、WA（%）、肺组织AngⅡ浓度和ERK1/2磷酸化水平均显著高于正常对照组;雷米普利组RVSP、RVHI、WT（%）、WA（%）、肺组织AngⅡ浓度和ERK1/2磷酸化水平均明显低于PAH组。结论雷米普利抑制MCT诱导的肺血管重构的机制可能与降低肺组织ERK1/2磷酸化水平有关。     

Pulmonary Hypertension after Hematopoietic Stem Cell Transplantation

Pulmonary hypertension (PH) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Given its nonspecific clinical presentation, it is likely that this clinical entity is underdiagnosed after HSCT. Data describing the incidence, risk factors, and etiology of PH in HSCT recipients are minimal. Physicians caring for HSCT recipients should be aware of this severe post-transplant complication because timely diagnosis and treatment may allow improved clinical outcomes. We summarize the pathophysiology, clinical presentation, diagnosis, and management of PH in HSCT recipients.     

Functional Class and Targeted Therapy Are Related to the Survival in Patients with Pulmonary Arterial Hypertension

Purpose

Pulmonary arterial hypertension (PAH) is an orphan disease showing poor prognosis. The purpose of study was to evaluate clinical factors influencing outcomes in PAH.

Materials and Methods

Patients who were diagnosed with PAH at a single center were reviewed retrospectively. Forty patients (34.9±14.5 years, 80% of female) were enrolled.

Results

Causes were congenital heart disease in 24 (60%), connective tissue disease in 8 (20%) and idiopathic PAH in 6 (15%). Sixteen patients (40%) were WHO functional class III or IV at the time of diagnosis. Twenty seven patients (67.5%) received molecular targeted therapy. During follow-up (53.6±45.5 months), 10 patients (25%) died and 1-, 2-, and 8 year survival rates were 91.3%, 78.7%, and 66.8%, respectively. As expected, median survival of patients with functional class I or II were significantly longer than patients with III or IV (p=0.041). Interestingly, patients with molecular targeted therapy showed longer survival than conventional therapy (p=0.021).

Conclusion

WHO functional class at the time of diagnosis was the strong predictor of survival, and molecular targeted therapy could significantly improve the survival. Therefore, early screening and intensive management would be crucial to improve the prognosis in the patient with PAH.     

Clinical Outcomes of Endoscope-Assisted Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension

PurposePulmonary thromboembolism is a potentially life-threatening condition in patients with heart disease; however, limited studies discussing long-term outcomes exist. This study aimed to investigate the long-term outcomes of pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), focusing on the improvement of functional class and right ventricular (RV) pressure.Materials and MethodsClinical data of patients with CTEPH were obtained from Yonsei Hospital between May 2012 and December 2021, and reviewed retrospectively. Twenty-six patients underwent endoscope-guided PEA during the study period, and the mean follow-up duration was 24.8±23.4 months.ResultsAfter PEA, most patients (88.5%) were weaned from inotropes without extracorporeal membrane oxygenation support during the first few days. Two patients (7.6%) had cerebrovascular accidents without neurological deficits. On echocardiography, the RV systolic pressure and tricuspid regurgitation grades significantly improved (p<0.001). Furthermore, the mean left ventricle end-diastolic diameter was significant increased (p=0.003), and the left ventricular end-systolic diameter increased (p<0.001). The median intensive care unit stay was 3.0±9.4 days, and median hospital stay 16.0±26.5 days. The 5-year survival rate was 95.5%, and the 5-year freedom rate of cardiac death was 100%. There was a marked improvement in New York Heart Association (NYHA) status (p<0.001). Cox regression suggested that the main pulmonary artery (MPA) involvement is a significant predictor of non-improvement in functional class post-PEA.ConclusionMortality rates are low and patients experience a marked improvement in NYHA class and health status after PEA. Moreover, MPA involvement may affect functional outcomes.     

肺动脉高压肺血管丛状病变的研究进展

Pulmonary arterial hypertension is defined as a multifactorial group of pulmonary vascular disorders characterized by a progressive increase in the pulmonary vascular resistance, resulting in right heart failure and premature death. The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. This article summarized the recent progress in the plexiform lesion including its occurrence, structure, animal models and molecular mechanism, which tried to predict the tendency of plexiform lesion study.     

疏血通对慢性阻塞性肺疾病合并肺动脉高压患者凝血状态及血清NO、NOS水平的影响

目的 观察疏血通治疗慢性阻塞性肺疾病(COPD)合并肺动脉高压(PAH)的疗效及对患者凝血状态及血清NO、NOS水平的影响.方法 将80例COPD合并PAH患者随机分为对照组和观察组,每组40例.对照组给予常规综合治疗,观察组在对照组基础上加用疏血通注射液治疗.分别于治疗前后检测患者血清一氧化氮(N0)、一氧化氮合成酶(NOS)、内皮素-1(ET-1)、抵抗素水平及血红蛋白(HB)、全血高切、低切黏度,比较两组治疗前后肺动脉收缩压、血气指标、肺功能指标及症状、体征改善情况.结果 治疗前,观察组与对照组各项测定指标差异均无统计学意义;治疗后,观察组较对照组血清NOS、NO水平明显升高(P＜0.05),ET、抵抗素水平明显降低(P＜0.05);全血高切黏度、全血低切黏度及HB水平明显降低(P＜0.05);肺动脉收缩压明显降低(P＜0.05),血气指标(PaO2、PaCO2、SaO2)、肺功能指标(FEV1、FEV1/FVC)及咳嗽、喘息、紫绀等症状、体征评分明显改善(P＜0.05).结论 疏血通辅助治疗COPD合并PAH,可通过调节血清NO、ET-1平衡,降低血清抵抗素水平,改善血管内皮功能,缓解血液高凝状态,降低肺动脉压,从而明显改善患者血气指标、肺功能指标及临床症状、体征.     

妊娠合并肺动脉高压严重程度对围生期结局的影响

目的 探讨妊娠合并肺动脉高压（PAH）患者的临床情况、处理方法及母儿结局。方法 回顾性分析2016年1月~2018年12月在华中科技大学同济医学院附属同济医院收治的26例妊娠合并肺动脉高压患者的临床资料,根据肺动脉收缩压分为轻中度PAH患者及重度PAH患者,比较不同程度PAH患者的病因、心功能分级、终止妊娠孕周、方式及母儿结局。结果 重度PAH患者心功能Ⅲ~Ⅳ级者占66.67%,高于轻中度PAH患者的42.86%,但差异无统计学意义（P＞0.05）;重度PAH患者终止妊娠孕周为（28.98±12.01）周,早于轻中度PAH患者的（36.79±3.00）周,差异有统计学意义（P＜0.05）;重度PAH患者全麻率高于轻中度PAH患者（66.67% vs 7.14%）,差异有统计学意义（P＜0.05）;重度PAH患者术中氧饱和度和输液量低于轻中度PAH患者、新生儿出生体重轻及小于胎龄儿发生率高,差异有统计学意义（P＜0.05）;重度PAH患者死亡率、新生儿窒息率高于轻中度PAH患者,但差异无统计学意义（P＞0.05）,重度PAH孕妇的新生儿平均体重、小于胎龄儿发生率高于轻中度PAH孕妇,差异有统计学意义（P＜0.05）。结论 妊娠合并PAH患者肺动脉压力越高,围生结局越差,重度PAH患者妊娠可危及母婴健康和生命,不宜妊娠,可妊娠的轻中度患者应在多学科专家的严密监护下妊娠,并选择恰当方式适时终止妊娠,以改善母儿结局。     

Activity of Angiotensin-Converting Enzyme in Hereditary Stress-Induced Arterial Hypertension

We measured activity of angiotensin-converting enzyme in plasma and tissue of NISAG and normotensive WAG rats. In different organs of NISAG rats, activity of this enzyme did not differ from the corresponding values of WAG rats, although enzyme activity in the plasma of NISAG rats was significantly lower than that of WAG rats. Since NISAG rats are characterized by low activity of renin in the renal cortex, it is hypothesized that NISAG rats simulate the low-renin hypertension, in which inhibition of activity of the angiotensin-production system results from elevation of arterial pressure of central origin. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 10, pp. 381–383, October, 2005     

De Novo Mutations in the BMPR2 Gene in Patients with Heritable Pulmonary Arterial Hypertension

A substantial proportion of patients with pulmonary arterial hypertension (PAH) have mutations in the Bone Morphogenetic Protein Receptor type‐2 (BMPR2) gene. PAH due to BMPR2 mutations is inherited as an autosomal dominant trait with several unique features, including a wide variety of mutations, reduced penetrance, a skewed gender ratio, variable expressivity and genetic anticipation. To address the genetic background of these unique features of BMPR2 mutation, we conducted a systematic analysis of 15 PAH families with BMPR2 mutation. The exonic protein coding sequence of BMPR2 was amplified by polymerase chain reaction and the products were sequenced directly to detect point mutations in BMPR2. Parental identification was carried out to confirm the parental relationship using multiplex 15 loci analysis. Combining mutation detection in family members with parental identification, we described three cases of de novo mutation in the BMPR2 gene by different modes in a PAH family. These de novo mutations may account for the wide variety of mutations in BMPR2. Taken together with the juvenile onset of the disease, there is possibly some balance of de novo mutations and untransmittable mutations which keeps the frequency of PAH low in the general population.