颈动-静脉分流法建立肺动脉高压模型

目的 利用颈动-静脉分流手术建立新西兰白兔动力性肺动脉高压模型.方法 将35只雄性新西兰白兔行右侧颈总动脉-颈外静脉吻合术,观察其肺动脉收缩压(SPAP)、肺动脉平均压(MPAP)和体动脉平均压(MAP),右心室/左心室+室间隔(RV/LV+S)比值,肺血管病变发生率.结果 术后观察3个月,35只兔存活并吻合口通畅兔的肺动脉高压形成率为82.35%,并有肺小动脉的病理形态学变化.SPAP为(46.3±11.2)mmHg,MPAP为(39.2±7.6)mmHg,MAP为(87.5±12.8)mmHg,RV/LV+S为59%±10%.结论 利用颈动-静脉分流手术可成功建立新西兰白兔动力性肺动脉高压模型.     

吸入依洛前列环素对先天性心脏病继发肺动脉高压患者的急性血管扩张试验

目的探讨吸入依洛前列环素（iloprost）对先天性心脏病（CHD）继发肺动脉高压（PAH）患者的肺动脉压力（PAP）、肺血管阻力（PVR）、心指数（CI）的影响。方法给予34例CHD继发PAH患者吸入iloprost和生理盐水,分别测量吸入iloprost和生理盐水后肺动脉收缩压（SPAP）、肺动脉舒张压（DPAP）、肺动脉平均压（MPAP）、PVR,CI、体循环平均压（MAP）和心率（HR）,比较两组指标的差异。结果吸入iloprost后PAH患者的SPAP、DPAP、MPAP和PVR下降,CI增加,MAP、HR无明显变化。结论吸入iloprost可安全有效地降低PAH患者的PAP和PVR,增加CI。     

前列地尔脂微球载体制剂对AECOPD合并慢性肺源性心脏病肺动脉高压疗效的临床研究

目的评价前列地尔脂微球载体制剂（L ipo PGE1）治疗AECOPD合并慢性肺源性心脏病肺动脉高压患者的疗效。方法 60例AECOPD合并慢性肺源性心脏病肺动脉高压患者随机分为治疗组和对照组,治疗组在常规治疗的基础上加用L ipoPGE1 10μg,对照组仅常规治疗。治疗前后检测肺动脉收缩压（SPAP）、肺动脉平均压（MPAP）、肺动脉舒张压（DPAP）、动脉血氧分压（PaO2）、动脉二氧化碳分压（PaCO2）、肺功能FEV1和FEV1/FVC。结果治疗后SPAP、MPAP、DPAP、PaCO2较治疗前明显降低,PaO2、FEV1和FEV1/FVC较治疗前显著增加,与对照组相比有显著差异（P〈0.05）。结论 PGE1治疗AECOPD合并慢性肺源性心脏病肺动脉高压能降低肺动脉压力,改善动脉血气和肺功能。     

中药治疗肺动脉高压的研究

一般认为,肺循环是一个高容低容低阻系统,正常人在静息状态下,在海平面呼吸新鲜空气,肺动脉收缩压（SPAP）为20～25 mmHg,舒张压为6～10 mmHg,平均压（MPAP）＜20 mmHg.肺动脉高压（pulmonary hypertension,PH）是指肺内循环系统发生高血压,MPAP＞ 25mmHg.2009年美国心脏病学会基金会/美国心脏学会（ACCF/AHA）制定的最新的肺动脉高压诊断标准是：在海平面,静息状态下,右心导管检查肺动脉平均压＞ 25 mmHg,肺毛细血管楔压（PCWP）≤15 mmHg.中医辩证中肺动脉高压属中医学“肺胀”、“喘证”和‘痰饮”等范畴.     

转移生长因子-β1和C-MYC癌基因在先心肺高压肺血管组织中的表达及意义

目的 研究左向右分流型先天性心脏病（CHD）合并肺动脉高压（PH）肺血管中转化生长因子-β1（TGF-β1）和原癌基因C-MYC的表达与PH病理的关系,探讨其在CHD并PH形成过程中的作用。方法 将112例左向右分流CHD患者按肺动脉平均压（MPAP）高低分为正常组（MPAP〈20 mmHg）33例,PH组（MPAP〉20mmHg）55例,重度PH组（MPAP〉70 mmHg）24例。三组均行肺活检术,免疫组化方法 检测肺血管组织中TGF-β1、C-MYC癌基因的定位及表达情况。结果 TGF-β1主要分布于肺动脉内皮细胞、肺动脉平滑肌和成纤维细胞等细胞的胞质中,且有片状分布。C-MYC癌基因主要分布于肺动脉内皮细胞、肺动脉平滑肌和成纤维细胞等细胞的胞核中。TGF-β1和C-MYC癌基因表达强度（A）随肺小动脉病理分级的加重而升高,在各组之间有明显差异（P〈0.05）,二者表达与病理分级有明显相关性（P〈0.05）。结论 TGF-β1和C-MYC癌基因在CH合并PH的形成过程中起重要生物学作用,TGF-β1对C-MYC癌基因起正性诱导作用,促进平滑肌细胞和成纤维细胞增殖。     

己椒苈黄汤对慢性肺源性心脏病患者肺动脉高压的影响

目的探讨己椒苈黄汤对慢性肺源性心脏病患者肺动脉高压的影响。方法连续纳入慢性肺源性心脏病80例患者,随机分为对照组（38例）和治疗组（42例）,对照组在常规治疗基础上加用硝苯地平,治疗组在常规治疗基础上加用己椒苈黄汤,疗程2周。观察治疗前后的临床症状、体征、血浆脑钠肽（BNP）、平均肺动脉压（MPAP）、左室射血分数（LVEF）及6 min步行距离（6MWD）。结果两组治疗后MPAP、LVEF、BNP、6MWD、临床症状体征等均较治疗前显著改善（P〈0.05或P〈0.01）,且治疗组MPAP、BNP、6MWD及临床症状体征的改善优于对照组（P〈0.05或P〈0.01）。结论己椒苈黄汤可有效降低慢性肺心病患者的平均肺动脉压及脑钠肽的水平,提高患者生存质量。     

高肺血流性肺动脉高压大鼠血清、肺动脉壁组织中VEGF和CTGF的表达变化及意义

目的观察高肺血流性肺动脉高压大鼠血管内皮生长因子（VEGF）、结缔组织生长因子（CTGF）的表达变化,并探讨其意义。方法将50只Wistar大鼠随机分为观察组30只和对照组20只。观察组大鼠用套管法做颈部分流手术,对照组仅做假手术。术后第1、4周测两组大鼠右心室收缩压（RVSP）,做血气分析计算Qp/Qs,取右肺组织性HE染色观察肺动脉形态学改变,并计算管壁厚度与血管外径比值（WT）。酶联免疫吸附法（ELISA）检测两组大鼠血清VEGF,Western blot法检测肺动脉组织中VEGF、CTGF。结果分流手术后观察组大鼠RVSP较对照组升高（P〈0.05）。Qp/Qs的平均值为2.01±0.29。肺部血管形态学观察显示在第4周WT%与对照组相比明显增高（P〈0.01）。与对照组相比,血清VEGF从第1周开始增高,第4周达较高水平（P均〈0.01）。术后1、4周观察组大鼠肺动脉组中VEGF、CTGF与对照组相比均显著增高（P均〈0.01）。结论高肺血流性肺动脉高压大鼠血清VEGF及肺动脉组织中VEGF、CTGF表达升高。VEGF、CTGF参与了高肺血流性肺动脉高压的发病过程。     

单向活瓣补片矫治间隔缺损合并重度肺动脉高压双向分流的术后效果分析

目的评估应用单向活瓣补片治疗合并重度肺动脉高压双向分流的先天性房室问隔缺损患者的术后效果。方法对32例伴有重度肺动脉高压双向分流的房室间隔缺损患者进行回顾性分析，进行常规补片矫治术的17例，进行单向活瓣补片矫治术的15例，术后分析两组的肺动脉收缩压（SPAP）与死亡率。结果常规补片矫治组死亡3例，死亡率17．65％，2例死于肺高压危象，1例死于右心衰；活瓣补片矫治组死亡1例，死于低血容量性休克与DIC，死亡率6．67％，单向活瓣补片矫治较之常规补片矫治的围手术期死亡率明显降低；常规补片组术前SPAP平均（93．2±22．6）mmHg，术后平均（85．4±17．9）mmHg，活瓣补片组术前SPAP平均（90．4±19．5）mmHg，术后平均（57．8±12．3）mmHg，大多数患者肺动脉压逐渐下降，其中活瓣补片组肺动脉压下降比常规补片组明显。活瓣矫治组回访5例，心功能均Ⅱ级；常规补片矫治组回访6例，心功能Ⅱ-Ⅳ级。结论单向活瓣补片矫治能有效地降低间隔缺损合并重度肺高压双向分流的围手术期死亡率及术后肺动脉收缩压，同时合理的围手术期治疗及术前综合评估，手术适应症的严格掌握是降低先心间隔缺损合并重度肺动脉高压双向分流患者死亡率、提高术后近中期生活质量的关键因素。     

室间隔缺损合并重度肺动脉高压围手术期处理

目的 :评估室间隔缺损合并重度肺动脉高压手术治疗围手术期处理的效果。方法 :选择 5 5例室间隔缺损合并重度肺动脉高压病例 ,在手术时放置Swan ganz导管 ,术后进行肺动脉压监测 ;2 0例用单向活瓣补片修补室缺 ,术后用超声心动图监测分流情况 ;用镇静 ,肌松 ,过度通气 ,血管扩张剂等治疗肺动脉高压危象。结果 :发现 7例持续肺动脉高压 ,死亡 2例 ;2 7例有肺动脉高压危象 ,死亡 2例 ;在严重肺动脉高压时 ,单向活瓣补片有右向左分流 ,肺动脉压下降后分流停止 ,未发现左向右分流。结论 :室间隔缺损合并重度肺动脉高压应把握好手术适应症 ,有不可逆的肺动脉高压患者禁止手术 ;Swan ganz导管在术后肺动脉高压处理上有重要作用 ;单向活瓣补片修补室缺能在术后发生重度肺动脉高压时发挥良好的右向左单向分流作用 ,肺动脉压下降后又能自动关闭。     

COPD合并肺动脉高压诊治分析

目的 探讨COPD合并肺动脉高压临床诊断,常规COPD治疗与强调戒烟和氧疗疗效对比.方法本研究随机选取我院就诊确诊为COPD合并肺动脉高压的患者90例为研究对象,随机分为对照组和实验组A、B,对照组仅针对COPD进行规范化治疗,实验组A采取常规的COPD系统化治疗外还特别强调戒烟,实验组B在实验组A治疗的基础上加上无创正压通气治疗.处理6周后,观察肺动脉压的动态变化情况和动脉血气分析情况.结果 实验组A及实验组B对改善肺动脉高压及患者动脉血气上明显高于对照组,P〈0.05.实验组B与实验组A相比,患者肺动脉压降低明显,P〈0.05.结论 规范治疗COPD对COPD合并肺动脉高压患者有很好的疗效,正压通气治疗及戒烟能明显增加患者疗效,改善患者预后.     

Gene transfer of endothelial nitric oxide synthase to the lung of the mouse in vivo. Effect on agonist-induced and flow-mediated vascular responses.

The effects of transfer of the endothelial nitric oxide synthase (eNOS) gene to the lung were studied in mice. After intratracheal administration of AdCMVbetagal, expression of the beta-galactosidase reporter gene was detected in pulmonary airway cells, in alveolar cells, and in small pulmonary arteries. Gene expression with AdCMVbetagal peaked 1 day after administration and decayed over a 7- to 14-day period, whereas gene expression after AdRSVbetagal transfection peaked on day 5 and was sustained over a 21- to 28-day period. One day after administration of AdCMVeNOS, eNOS protein levels were increased, and there was a small reduction in mean pulmonary arterial pressure and pulmonary vascular resistance. The pressure-flow relationship in the pulmonary vascular bed was shifted to the right in animals transfected with eNOS, and pulmonary vasodepressor responses to bradykinin and the type V cGMP-selective phosphodiesterase inhibitor zaprinast were enhanced, whereas systemic responses were not altered. Pulmonary vasopressor responses to endothelin-1 (ET-1), angiotensin II, and ventilatory hypoxia were reduced significantly in animals transfected with the eNOS gene, whereas pressor responses to norepinephrine and U46619 were not changed. Systemic pressor responses to ET-1 and angiotensin II were similar in eNOS-transfected mice and in control mice. Intratracheal administration of AdRSVeNOS attenuated the increase in pulmonary arterial pressure in mice exposed to the fibrogenic anticancer agent bleomycin. These data suggest that transfer of the eNOS gene in vivo can selectively reduce pulmonary vascular resistance and pulmonary pressor responses to ET-1, angiotensin II, and hypoxia; enhance pulmonary depressor responses; and attenuate pulmonary hypertension induced by bleomycin. Moreover, these data suggest that in vivo gene transfer may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders.     

前列地尔对慢性肺源性心脏病肺动脉高压疗效的临床研究

目的探讨前列地尔对慢性肺源性心脏病肺动脉高压的治疗效果,为临床提供参考。方法选择慢性肺源性心脏病伴肺动脉高压患者130例,随机分为两组,每组65例,对照组进行常规治疗,治疗组在对照组治疗基础上给予前列地尔治疗,比较两组疗效。结果治疗组患者治疗后,其DPAP、SPAP和MPAP的值分别为(11.9±2.5)mmHg、(28.6±3.8)mmHg、(16.3±2.5)mmHg,均较治疗前显著降低;对照组患者治疗后,其DPAP、SPAP和MPAP的值分别为(17.2±3.1)mmHg、(35.9±7.2)mmHg、(31.9±6.1)mmHg,均较治疗前显著降低;治疗组治疗后,DPAP与SPAP显著低于对照组;治疗组治疗后,PaO2、FEV1、FEV1/FVC的值分别为(66.84±8.03)mmHg、(81.41±11.13)%、(90.52±13.51)%,较治疗前显著升高,PaCO2值为(52.50±7.11)mmHg,较治疗前显著降低;对照组治疗后,PaO2、FEV1、FEV1/FVC的值分别为(55.88±7.72)mmHg、(77.39±12.11)%、(79.25±11.01)%,较治疗前显著升高,PaCO2值为(56.6±0.42)mmHg,较治疗前显著降低;治疗组患者治疗后的PaO2值显著高于对照组,差异均有统计学意义(P0.05)。结论前列地尔治疗慢性肺源性心脏病肺动脉高压疗效显著,患者不良反应少,其临床效果优于常规治疗,用药后患者肺动脉压明显降低,症状得到明显缓解,说明前列地尔注射液在治疗慢性肺源性心脏病肺动脉高压方面具有较高的临床应用价值。     

New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure

STUDY OBJECTIVES: Mean pulmonary artery pressure (MPAP) and systolic pulmonary artery pressure (SPAP) are used interchangeably to define pulmonary hypertension (PH). We tested the hypothesis that the measurement of MPAP and SPAP is redundant in resting humans over a wide pressure range. DESIGN: Prospective, observational study. SETTING: Catheterization laboratory in a university hospital. PATIENTS: This study involved 31 patients, as follows: primary PH, nine patients; chronic pulmonary thromboembolism, seven patients; venous PH, six patients; and control subjects with normal pulmonary artery pressure, nine patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: High-fidelity pulmonary artery pressures were obtained when patients were at rest. Over the wide MPAP range that was under study (10 to 78 mm Hg), MPAP and SPAP were strongly related (r(2) = 0.98). Regression analysis performed on the first 16 subjects (test sample) allowed us to propose a formula (MPAP = 0.61 SPAP + 2 mm Hg), the accuracy of which was confirmed in the remaining 15 subjects (validation sample bias, 0 +/- 2 mm Hg). If PH was defined by an SPAP in excess of 30 or 40 mm Hg, this corresponded to an MPAP in excess of 20 or 26 mm Hg. If PH was defined by an MPAP of > 25 mm Hg, this corresponded to an SPAP of > 38 mm Hg. CONCLUSIONS: In resting humans, MPAP can be accurately predicted from SPAP over a wide pressure range. The new formula may help to refine the threshold pressure values used in the diagnosis of PH. Further studies are needed to test the hypothesis that our formula may allow the noninvasive prediction of MPAP from Doppler-derived SPAP values.     

Gene transfer of endothelial nitric oxide synthase improves nitric oxide-dependent endothelial function in a hypertensive rat model

OBJECTIVE: We have shown previously that there is a relative nitric oxide deficiency at the level of vascular endothelium in the stroke-prone spontaneously hypertensive rat (SHRSP), a model of human essential hypertension, as compared to its normotensive reference strain Wistar Kyoto (WKY) rat. The aim of the current study was to investigate whether adenoviral-mediated gene transfer of an endothelial nitric oxide synthase (eNOS) cDNA (AdCMVeNOS) into carotid arteries of the SHRSP may improve endothelial function. METHODS: Enzyme activity of the recombinant eNOS protein encoded by AdCMVeNOS was tested using a Griess assay in endothelial cells in culture. Left carotid arteries of SHRSP were surgically isolated and exposed to either the AdCMVeNOS or control beta-galactosidase-containing virus, (2 x 10(9) pfu/ml) ex vivo and in vivo. The vessels were harvested 24 h after surgery and analysed by Western blotting, immunohistochemistry and by examining endothelial function ex vivo. RESULTS: Cultured endothelial cells showed almost 100% transduction with both viruses and a dose response of eNOS expression showed a five-fold increase in nitrite production for AdCMVeNOS with no change for beta-galactosidase-containing virus. Western blotting demonstrated a significant increase of eNOS expression in vessels infused with AdCMVeNOS when compared to controls. Immunohistochemistry showed highly positive staining with monoclonal antibodies against eNOS in the intact endothelial cells of the AdCMVeNOS infused vessels. The areas under the curve of the concentration responses to phenylephrine (10(-9) to 3 x 10(-6) M) in the absence and presence of NG-nitroarginine methyl ester (100 microM) showed increased basal nitric oxide bioavailability in the carotid arteries infused with AdCMVeNOS compared to the control (n = 6 for each; P = 0.0069; 95% CI, 0.864 to 3.277). CONCLUSIONS: Our results show that AdCMVeNOS is an effective tool for vascular gene transfer and that it can improve endothelial NO availability in the SHRSP, a genetic model of essential hypertension and endothelial dysfunction.     

肝细胞生长基因转染诱导肺高压模型动物肺血管生成的实验研究

目的 在家兔高动力性肺动脉高压模型上经气管途径转染携带人肝细胞生长因子基因的重组腺病毒(Ad-HGF),探讨外源HGF基因转染诱导侧支肺血管生成的可行性.方法 1月龄幼兔正中开胸,行左无名动脉与主肺动脉吻合,通过持续左向右分流,3个月后建立高动力性肺动脉高压模璎.将模型动物随机分为对照组、GFP转染组、单次HGF治疗组和重复HGF治疗组.HGF治疗组(单次或1周后重复)通过气管内滴入的方法转染Ad-HGF.2周后,通过RT-PCR和免疫组织化学检测HGF基因和蛋白表达.分别在基因转染后14 d和30 d通过免疫组织化学榆测肺微血管和小动脉密度.1个月时,肺血管造影观测侧支血管建立情况.结果 气管内滴入Ad-HGF后2周,肺组织RNA提取后凝胶电泳显示有484 bp长的特异性片段出现,免疫组化町检测到肺血管内皮、肺泡上皮细胞内HGF表达.肺组织病理切片观察可见HGF基因治疗组肺血管密度(单次HGF治疗组和重复HGF治疗组)明显高于对照组和GFP转染组,增多的血管以微血管为主,1个月后,肌性肺动脉明显增多.肺血管造影证实HGF基因治疗组侧支血管较对照组和GFP转染组丰富.结论 外源性HGF基因经气管转染,早期(2周内)以诱导肺微血管新生为主,后期(1个月时)可促进肺小动脉生成.     

Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice

It has been shown that mice deficient in the gene coding for endothelial nitric-oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary vascular resistance. In the present study, the effect of transfer to the lung of an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial pressure and pulmonary vascular resistance was investigated in eNOS-deficient mice. One day after intratracheal administration of AdCMVeNOS to eNOS(-/-) mice, there was an increase in eNOS protein, cGMP levels, and calcium-dependent conversion of l-arginine to l-citrulline in the lung. The increase in eNOS protein and activity in eNOS(-/-) mice was associated with a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance when compared with values in eNOS-deficient mice treated with vehicle or a control adenoviral vector coding for beta-galactosidase, AdCMVbetagal. These data suggest that in vivo gene transfer of eNOS to the lung in eNOS(-/-) mice can increase eNOS staining, eNOS protein, calcium-dependent NOS activity, and cGMP levels and partially restore pulmonary arterial pressure and pulmonary vascular resistance to near levels measured in eNOS(+/+) mice. Thus, the major finding in this study is that in vivo gene transfer of eNOS to the lung in large part corrects a genetic deficiency resulting from eNOS deletion and may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders in which eNOS activity is reduced.     

Pulmonary hypertension in systemic lupus erythematosus

A prospective echocardiographic and clinical study was performed on 84 Chinese patients with systemic lupus erythematosus (SLE) and 99 controls to investigate the prevalence and the mechanism of pulmonary hypertension (PH) in SLE. Comparison between Doppler estimation and catheterization measurement was made in 12 cases to validate the predictive method. Compared to normal subjects, lupus patients had significantly increased sys-tolic pulmonary artery pressure (SPAP) (29.59±12.52 vs 19.64±5.82, P<0.001), mean pulmonary artery pressure (MPAP) (15.11±7.36 vs 10.21±4.72, P<0.001) and total pulmonary resistance (TPR) (315.85±190.65 vs 220.37± 55.92, P<0.001). Nine of the 84 patients presented PH, defined as SPAP >30 mmHg and MPAP >20 mmHg. Pulmonary hypertensive patients had higher serum endothelin (ET) than non-pulmonary hypertensive patients, were more commonly in active stages, and presented Raynaud's phenomenon and rheumatoid factors. ET level was correlated with echocardiographic pulmonary pressure. Pulmonary hypertension commonly occurs in Chinese patients with SLE (11%), and it correlates with the lupus activity and the elevation of serum endothelin. Received: 29 April 1998 / Accepted: 30 September 1998