中医药防治慢阻肺肺动脉高压的临床研究进展

慢性阻塞性肺疾病（COPD）是一种临床常见病和多发病,由于长期的缺氧,其后期往往出现肺动脉高压而导致慢性肺源性心脏病发生。慢性阻塞性肺疾病肺动脉高压在肺心病的发生、发展过程中起着重要作用。肺动脉压的高低,直接关系到COPD患者的预后。

汉防己甲素对犬缺氧性肺动脉高压模型血流动力学的作用及对血气水平的影响

本文研究了汉防己甲素（ＴＥＴ）对犬缺氧性肺动脉高压时肺循环血流动力学及血气的影响。在急性肺泡缺氧犬模型，静脉注射ＴＥＴ使缺氧引起的肺动脉高压恢复４２％，但对Ｐｓａ无显著性影响，ＴＥＴ仪由缺氧引起下降的ＣＯ及升高的ＴＰＶＲ和ＳＶＲ恢复到接近呼吸室内空气时的水平。ＴＥＴ对动脉血无分压（ＰａＯ２）和血氧饱和度（ＳａＯ２）无形响，但由于其使ＣＯ升高，故明显增大氧搬运系数（ＴＯ２）．直线回归分析在明：ＴＥＴ降低肺动脉高压的作用与缺氧时肺动脉压升高的水平密切相关。我们的结论是：在缺氧性肺动脉高压犬，ＴＥＴ能明显降低升高的肺动脉压和肺血管阻力，并能提高心输出量和氧搬运能力，而对系统循环和血气水平无明显影响。

肺动脉高压药物治疗进展

肺动脉高压分为原发性和继发性肺动脉高压。肺动脉高压具有药物治疗效果和预后差的特点。血管内皮功能减退与肺动脉高压的发生发展具有极其密切的关系。前列环素类似物、内皮素受体拮抗药等是新开发的有效治疗肺动脉高压的药物。

肺心平对肺心病肺动脉高压大鼠肺血管重建的影响

目的:研究中药复方肺心平对肺心病肺动脉高压大鼠肺血管重建的影响.方法:以2%野百合碱胺(MCT)60mg/Kg一次性腹腔注射,复制大鼠肺心病肺动脉高压模型.用右心室导管技术测定肺动脉压;用光、电镜观察肺动脉血管形态学方面的变化.结果:模型组与正常空白对照组比较肺动脉压明显升高,光、电镜下肺内肌型动脉和腺泡动脉中膜厚度比例均明显增大,肺血管内皮细胞肿胀,呈立方形或柱状突向血管腔内,核形变圆,甚或坏死脱落.而肺心平组和卡托普利组与模型组比较,肺动脉压明显下降,肺动脉血管结构明显改善;肺心平高剂量组稍优于低剂量组和卡托普利组.结论:肺心平能明显降低肺心病肺动脉高压大鼠的肺动脉压,改善肺血管结构,逆转肺血管重建.

妊娠合并肺动脉高压麻醉的临床分析

目的观察低剂量椎管内麻醉联合伊洛前列素和全身麻醉联合前列腺环素用于妊娠合并肺动脉高压麻醉的临床效果,以及两者的优点及区别。方法对40例经临床明确诊断为妊娠合并肺动脉高压,同时要进行剖宫产手术的产妇随机分为A组和B组,每组分别为20例。麻醉方法和降低肺动脑高压的药物选择分别为:A组产妇采取低剂量椎管内麻醉联合伊洛前列素的方法;B组产妇采取全身麻醉联合前列腺环素的方法,观察其麻醉效果及对产妇在分娩过程中出血量及肺动脉高压的控制情况。结果 A组和B组研究对象在阻滞起效、阻滞完全时间及麻醉效果方面,低剂量椎管内麻醉联合伊洛前列素的麻醉效果明显好于全身麻醉联合前列腺环素组,差异有统计学意义(P<0.05),同时,低剂量椎管内麻醉联合伊洛前列素组研究对象在分娩中的出血量少于全身麻醉联合前列腺环素组,差异有统计学意义(P<0.05)。结论在对接受妊娠合并肺动脉高压产妇进行剖宫产手术时,采用低剂量椎管内麻醉联合伊洛前列素的麻醉方式较全身麻醉联合前列腺环素的麻醉效果更好。

Pre-and postoperative systemic hemodynamic evaluation in patients subjected to esophagogastric devascularization plus splenectomy and distal splenorenal shunt:A comparative study in schistomomal portal hypertension

AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. RESULTS: Preoperative evaluation revealed (mean ± SD) an increased cardiac index (4.78 ± 1.13 L/min per m2),associated with a reduction in systemic vascular resistance index (1457 ± 380.7 dynes.s/cm5.m2). The mean pulmonary artery pressure (18 ± 5.1 mmHg) as well as the right atrial pressure (7.9 ± 2.5 mmHg) were increased,while the pulmonary vascular resistance index (133 ± 62 dynes.s/cm5.m2) was decreased. Four days after EGDS,a significant reduction in cardiac index (3.80 ± 0.4 L/min per m2,P < 0.001) and increase in systemic vascular resistance index (1901.4 ± 330.2 dynes.s/cm5. m2,P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 ± 4.7 mmHg,P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 ± 102.9 dynes.s/cm5.m2). Four days after DSRS,a non-significant increase in cardiac index (5.2 ± 0.76 L/min per m2) and systemic vascular resistance index (1389 ± 311 dynes.s/cm5.m2) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 ± 5.2 mmHg),right cardiac work index (1.38 ± 0.4 kg.m/m2) and right ventricular systolic work index (16.3 ± 6.3 g.m/m2),without significant changes in the pulmonary vascular resistance index (139.7 ± 67.8 dynes.s/cm5.m2). CONCLUSION: The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS,but was maintained in patients who underwent DSRS. Similarly,the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.

THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Clinical and hemodynamic profiles of elderly patients with pulmonary arterial hypertension： a single center, prospective study

Backgrounds Pulmonary arterial hypertension （PAH） was previously considered an illness that affects mostly the young, but now it is also increasingly recognized in the elderly. The aim of this study was to compare the features of elderly versus younger patients diagnosed with PAH, and to define the prognostic factors which affect their long-term survival. Methods In this prospective, single center study, the clinical, echocardiographic, hemodynamic characteristics, and the outcomes of younger （18-65 years） and elderly （〉 65 years） patients with definitive diagnosis of precapillary PAIl were compared. Results A total of 119 patients were analyzed in this study; 43 were elderly （mean age： 71.5 ± 5.5 years）, while 76 were non-elderly （mean age 44.5 ±15.2 years）. During the mean follow-up duration of 26.8 ±25.0 months, 43 deaths occurred, 17 of which were among the elderly group, with 28 among non-elderly group. Comparison of baseline parameters showed that 6 min walking distance, hemoglobin levels, pulmonary artery pressures and pulmonary vascular resistance were significantly lower; and estimated glomerular filtration rate, body mass index, E/e＇ and pulmonary capillary wedge pressure were significantly higher in the elderly group than in the younger group. Survival analysis demonstrated that the independent predictors of death were tricuspid plane annular systolic excursion （TAPSE; HR： 1.272, 95% CI： 1.079-1.499, P = 0.004） and uric acid （HR： 1.291, 95% CI： 1.042-1.600, P = 0.019） in the elderly group. In contrast, in the non-elderly group, higher brain natriuretic peptide （HR： 1.002, 95% CI： 1.001-1.004, P 〈 0.001） and higher right atrial pressure （HR： 1.128, 95% CI： 1.026-1.241, P = 0.013） values were the only parameters associated with mortality. Conclusions Our data suggest that elderly PAH patients have a unique clinical and hemodynamic profile, with totally different prognostic markers compared to younger PAH patients.

Proteomic analysis of the serum in patients with idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension(IPAH) is a rare disease of unknown etiology.The exact pathogenesis of pulmonary arterial hypertension is still not well known.In the past decades,many protein molecules have been found to be in-volved in the development of IPAH.With proteomic techniques,profiling of human plasma proteome becomes more feasible in searching for disease-related markers.In present study,we showed the protein expression profiles of the serum of IPAH and healthy controls after depleting a few high-abundant proteins in serum.Thirteen spots had changed significantly in IPAH com-pared with healthy controls and were identified by LC-MS/MS.Alpha-1-antitrypsin and vitronectin were down-regulated in IPAH and may be valuable candidates for further explorations of their roles in the development of IPAH.

INCREASED EXPRESSION OF PDGF AND C-MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXIA

The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known.The present study examined gene expression of platelet-derived growth factor(PDGF)-A and -B chain and proto-oncogene,c-myc,in lung tissue and pulmonary artery of rats exposed to hypoxia and compared to those levels of gene expression in normal rats.Normal lungs and pulmonary artery expressed PDGF-A chain transcript of 1.7 kb and PDGF-B chain transcript of 3.5 Kb.The c-myc transcript of 2.2 kb was expressed as well. After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and cmyc were elevated significantly compared with those of control rats.PDGF-A chain mRNA increased after hypoxia for 7 days,and then declined.These results suggest that activation of autocrine and/or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertensive rats.

Home-made fenestrated amplatzer occluder for atrial septal defect and pulmonary arterial hypertension

We report the management of a patient with secundum atrial septal defect （ASD） and severe pulmonary hypertension. A 65-year-old male with recently diagnosed atrial septal defect was referred to our centre for decompensated right heart failure with rest and exercise induced dispnea and severe pulmonary hypertension. Right heart catheterization confirmed a mean pulmonary pressure of about 55 mmHg and a Qp/Qs of 2.7. An occlusion test with a compliant large balloon demonstrated partial fall of pulmonary arterial pressure. The implantation of a home-made fenestrated Amplatzer ASD Occluder （ASO） was planned in order to decrease left-to-right shunt and promote further decrease of pulmonary arterial pressure in the long-term. Thus, by means of mechanical intracardiac echocardiography study with a 9F 9 MHz Ultralce catheter （Boston Scientific Corp.）, we selected a 34 mm ASO for implantation. Four millimeter fenestration was made inflating a 4 mm non-compliant coronary balloon throughout the waist of the ASO, which was successfully implanted under intmcardiac echocardiography. After six months, a decrease of pulmonary arterial pressure to 24 mmHg and full compensated right heart failure was observed on transthoracic echocardiography and clinical examination. This case suggests that Wanscatheter closure with home-made fenestrated ASD in elderly patients with severe pulmonary hypertension is feasible.

Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

Portopulmonary hypertension(PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension,with or without advanced hepatic disease.Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state.Similar signs of advanced liver disease can be observed in severe PPH,with ascites and lower extremity edema.Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation(LT).We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis.Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years,it was necessary to send him to the intensive care unit after operation.Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.

Which prognostic factors should be used in pulmonary arterial hypertension in elderly patients？

In recent times, the prevalence of pulmonary arterial hypertension creased prevalence of hypertension, diabetes, obesity, arterial stiffness, （PAH） is more commonly seen among elderly populations. The inas well as diastolic dysfunction, may cause endothelial dysfunction and affect pulmonary vasculature. Furthermore, older patients have certain differences in clinical characteristics and outcomes. In this article the special characteristics of aging in PAH patients have been reviewed, while the risk predictors of elderly patients are also discussed.

How to select the appropriate candidate of pulmonary arterial hypertension： specific therapy in elderly patients with pulmonary hypertension

Recent reports from pulmonary arterial hypertension （PAH） registries suggest that the mean age at diagnosis is increasing in a growing proportion of elderly patients. The combination of several reasons such as aging popula- tion, increase in life expectancy, growing PAH awareness of physicians and patients, and availability of more treatment options could explain the changing picture of PAH. PAH should be considered as an emerging entity in the elderly.

ROLE OF COLLAGEN METABOLISM CHANGES IN THE PATHOGENESIS OF PULMONARY HYPERTENSION IN RATS AND ITS REVERSIBILITY

Pulmonary arterial pressure (PAP) was increased obviously in rats after 3 days of normobaric hypoxic exposure and reached a maximum at 14 days of hypoxia. It remained at the same level during prolonged hypoxic exposure of up to 21 days. Right ventricular weight (RV/LV +S) and hydroxyproline (HP) content in the pulmonary artery began to increase at day 7. HP content had increased much faster than the relative rate of increase of PAP after 14 days, but HP content in the thoracic aorta showed no change. The relative proportion of type Ⅰto Ⅲ collagen increased singnificantly, and compliance of the pulmonary vessels obviously decreased. All parameters returned to the normal range within 14 days after recovery from hypoxia, except for HP content as expressed per vessel. 764-3 treatment obviously attenuated most of the changes caused by hypoxia, though it had no effect on compliance of the pulmonary vessels. It is suggested that collagen, especially type Ⅰcollagen, accumulation may play an important role in maintaining pulmonary hypertension. 764-3 has certain protective effects and may be useful in the treatment of early chronic obstructive pulmonary disease.

Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

Fathal pulmonary hypertension after distal splenorenal shunt in schistosomal portal hypertension

Mansonic schistosomiasis is the main cause of portal hypertension in Brazil. Hepatosplenic (HS) form is manifested by hepatomegaly mainly on the left hepatic lobe associated with large splenomegaly and bleeding due to esophageal varices with high mortality rates.

EFFECT OF HYPOXIA ON DNA SYNTHESIS AND C－MYC GENE EXPRESSION OF PULMONARY ARTERY SMOOTH MUSCLE CELLS

The neonate is particularly susceptible to the development of hypoxic pulmonary hypertension. The present study was undertaken to observe the effect of hypoxia on DNA synthesis and c-myc gene expression between newborn calf and adult bovine PASMC in vilro. DNA synthesis measured by 3H- TdR incorporation was increased after hypoxic challenge for 24h. Hypoxia enhanced the increment in 3H-TdR incorporation induced by EGF. Northern blot analysis revealed that PASMC cultured in both normoxia and hypoxia expressed c- myc gene transcript of 2. 2Kb ,but there is a higher 2. 2Kb mRNA expression in hypoxic PASMC than that in normoxia. We speculate that newborn calf PASMC exhibited potential response to hypoxia than adult,which was augmented by EGF. Enhanced c-myc gene expression may lead to a great understanding of the mechanism of PASMC growth in the development of pulmonary hypertension.