Characterizing pulmonary blood flow distribution measured using arterial spin labeling

The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head‐down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head‐down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post‐tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels. Copyright © 2009 John Wiley & Sons, Ltd.     

Pulmonary arteritis with pulmonary arterial thrombosis and recurrent endopulmonary embolization

Summary A 41-year-old woman underwent medical examination for superficial thrombophlebitis of both lower legs. Incidentally a chronic myelogenous leukemia was diagnosed and chemotherapeutically treated. Three weeks after the first attendance the patient again suffered superficial thrombophlebitides of all extremities. Clinically she exhibited symptoms of recurrent mild pulmonary embolization. Contrast venography revealed no signs of deep venous thrombosis of legs, pelvis, or cava inferior. Despite continuous full-dose intravenous heparin administration the patient died, with signs of fulminant pulmonary embolization. Surprisingly, necropsy revealed a complete thrombotic occlusion of the pulmonary arterial system caused by pulmonary arteritis with signs of recurrent pulmonary embolization from a parietal truncus pulmonalis thrombosis. In addition, an appositional growth of parietal thrombi central from peripheral arterial ramifications had occurred. Simultaneously, superficial thrombophlebitis of all extremities was observed without any additional signs of general vasculitis. There was no strong evidence for a causal relationship between the chronic myelogenous leukemia and pulmonary arteritis nor for any other underlying systemic disorder. Therefore we consider the pulmonary arteritis a possibly primary one. This very rare disease is discussed with respect to the literature.Abbreviation CML chronic myelogenous leukemia     

Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.     

肺部超声对重症肺部感染患者肺通气的评估价值

目的:探讨肺部超声评价重症肺部感染患者通气情况的应用价值。方法:选取88例重症肺部感染患者,采用半定量方法对肺部超声征象进行评分,以CT检查结果为金标准,分析肺部超声评分与患者肺通气的关系;同时分析存活和死亡患者临床资料、肺部超声评分的差异,以及肺部超声评分预测患者死亡的价值。结果:88例患者全肺超声评分平均为（18.50±2.12）分,全肺CT值平均为（-620.50±88.13） HU,不通气/低通气肺组织比例平均为（10.41±3.35）%,正常通气肺组织比例平均为（71.54±6.69）%,过度通气肺组织比例平均为（17.65±4.11）%;患者肺部超声评分与全肺CT值、不通气/低通气肺组织比例呈正相关（r=0.775、0.648, P<0.05）,与正常通气肺组织比例、过度通气肺组织比例无明显相关性（r=-0.170、0.046, P>0.05）;死亡组患者年龄、糖尿病比例、APACHEⅡ评分、肺泡-动脉氧分压差、机械通气治疗和肺部超声评分分别为（59.28±8.12）岁、44.83%、（22.19±2.40）分、（344.40±82.29） mmHg、72.41%和（20.20±1.72）分,明显高于存活组（P<0.05）,而氧合指数为（104.42±21.18）,明显低于存活组（P<0.05）;Logistic回归分析结果显示:年龄、APACHEⅡ、肺部超声评分是重症肺部感染患者死亡的影响因素（OR=1.758、2.841、2.440, P<0.05）;肺部超声评分预测重症肺部感染患者死亡的ROC曲线下面积为0.901（95%CI:0.836~0.966）,截断值为20分,灵敏性和特异性分别为82.80%和84.70%。结论:肺部超声可以作为重症肺部感染患者肺通气的评估指标,同时其在预测患者预后方面有一定应用价值。     

Character of the pulmonary circulation in experimental pulmonary edema dated by artificial ventilation

Laboratory of Pathophysiology of Respiration and Bioengineering Laboratory, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR B. B. Moroz.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 126–128, February, 1990.     

中介素抑制高肺血流性肺动脉高压大鼠肺组织胶原生成

 目的:研究中介素（IMD）对高肺血流性肺动脉高压大鼠肺组织胶原生成和沉积的调节作用及其机制。方法: 健康雄性SD大鼠20只,随机分为对照组（n=7）、分流组（n=7）和分流+IMD组（n=6）。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+IMD组大鼠,皮下埋微量渗透泵持续给予IMD 1.5 μg·kg-1·h-1。继续饲养2周后,比较各组大鼠肺动脉平均压（mPAP）、肺中、小动脉相对中膜厚度（RMT）,肺组织羟脯氨酸、Ⅰ和Ⅲ 型胶原、骨形成蛋白-2（BMP-2）含量和I、III型前胶原mRNA表达水平。结果: 与对照组相比,分流组大鼠mPAP明显上升,肺中、小动脉RMT明显增加,肺组织羟脯氨酸和Ⅰ、Ⅲ型胶原含量明显增多,Ⅰ、Ⅲ型前胶原mRNA表达上调,BMP-2含量明显增多。IMD则使分流大鼠肺动脉压力明显回降,肺血管结构改变缓解,胶原沉积减少,BMP-2含量降低,Ⅰ、Ⅲ 型前胶原mRNA表达下调。结论: IMD可通过抑制高肺血流大鼠肺组织胶原生成和沉积,缓解高肺血流性肺动脉高压和肺血管结构重构形成,该作用可能与BMP-2途径有关。     

肾上腺髓质素对高肺血流大鼠肺组织氧化应激的调节作用

目的:研究肾上腺髓质素(ADM)对高肺血流性肺动脉高压大鼠肺组织氧化应激的调节作用及其机制。方法:健康雄性SD大鼠随机分为对照组、分流组和分流+ADM组。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+ADM组大鼠皮下埋微量渗透泵持续予ADM 1.5μg·kg~(-1)·h~(-1)。继续饲养2周后,右心导管法测定平均肺动脉压(mPAP)和右心室/(左心室+室间隔)重量比值,检测肺中、小肌型动脉相对中膜厚度(RMT),比色法测定肺组织匀浆丙二醛(MDA)含量、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性,Western blot法检测肺组织还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)的表达。结果:与对照组相比,分流组大鼠的mPAP、右心室肥厚程度以及肺中、小肌型动脉RMT均明显增加,肺组织MDA含量明显升高,T-AOC、SOD活性和GSH-Px活性均明显降低,肺组织NOX4表达明显升高。ADM使肺动脉压力明显回降,右心室肥厚程度减轻,肺血管结构改变缓解,肺组织MDA含量明显下降,T-AOC、SOD活性和GSH-Px活性明显升高,肺组织NOX4表达明显降低。结论:ADM能够抑制大鼠高肺血流性肺动脉高压和肺血管结构重构形成中的氧化应激反应,作用机制可能与其下调肺组织NOX4表达以及增强抗氧化活性有关。     

POEMS综合征合并肺动脉高压临床分析

目的 分析POEMS综合征合并肺动脉高压患者的临床特点.方法 回顾性分析北京协和医院确诊POEMS综合征患者的临床资料,并将超声心动图证实合并肺动脉高压的患者与肺动脉压正常的患者以及未行超声心动检查的患者的临床表现进行比较,描述合并肺动脉高压的POEMS综合征患者的临床特点.结果 POEMS综合征117例,合并肺动脉高压49例,肺动脉压正常33例,未行超声心动检查35例;肺动脉高压患病率41.9%.肺动脉高压组临床表现主要为胸闷、憋气,发生率42.9%(21/49),显著高于另外两组(P≤0.05),但一半以上患者无明显胸闷、憋气;肺动脉高压组并发胸水、腹水、心包积液发生率较另外两组高(P≤0.01),其他临床表现无显著差异.结论 POEMS综合征超声心动图检测肺动脉高压患病率高达40%以上,但半数以上患者无胸闷、憋气,提示在POEMS综合征诊治过程中应重视肺动脉高压的筛查和早期发现.     

肺动脉高压患者生活质量及其影响因素

目的：了解肺动脉高压患者的生活质量状况并探讨其影响因素。方法：采用整群抽样的方法选择2014年6月至2015年6月期间在中南大学湘雅医院住院治疗的68例肺动脉高压患者作为研究对象。采用一般资料问卷、中文版简明健康调查量表(Short Form 36 Health Survey Questionnaire,SF-36)对其进行调查,运用单因素分析及多元线性回归法分析其影响因素。结果：肺动脉高压患者SF-36量表各维度评分均低于常模,差异均有统计学意义(P<0.05)。影响生活质量生理健康的因素为性别、6分钟步行试验距离(6-minute walking distance,6MWD)、是否合并右心衰竭、是否坚持氧疗;影响生活质量心理健康的因素为性别、文化程度、有无医疗保险。结论：肺动脉高压患者生活质量不高。医护人员应对女性、文化程度低、无医疗保险、6MWD短、合并右心衰竭、未坚持氧疗的患者给予更多的关注。     

Dynamics of regulation of pulmonary ventilation during transition from rest to exertion

The dynamics of regulation of the pulmonary ventilation during the transition from rest to exertion of different power (from 200 to 1000 kg·m/min) was analyzed by means of a mathematical model in experiments on healthy subjects who varied in their standard of training. The half-period of the transition process for ventilation was found to increase initially with an increase in the power of exertion. Later, when the critical power was reached, it began to fall. In healthy untrained subjects the critical point was at the level of approximately 500 kg·m/min, whereas in trained athletes the point was shifted to the region of more strenuous exertion.Department of Experimental and Clinical Physiology, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 131–133, August, 1979.     

The role of platelets in the development and progression of pulmonary arterial hypertension

Pulmonary arterial hypertension is a multifactorial disease characterized by vasoconstriction, vascular remodeling, inflammation and thrombosis. Although an increasing number of research confirmed that pulmonary artery endothelial cells, pulmonary artery smooth muscle cells as well as platelets have a role in the pulmonary arterial hypertension pathogenesis, it is still unclear what integrates these factors. In this paper, we review the evidence that platelets through releasing a large variety of chemokines could actively impact the pulmonary arterial hypertension pathogenesis and development. A recent publication revealed that not only an excess of platelet derived cytokines, but also a deficiency may be associated with pulmonary arterial hypertension development and progression. Hence, a simple platelet blockade may not be a correct action to treat pulmonary arterial hypertension. Our review aims to analyse the interactions between the platelets and different types of cells involved in pulmonary arterial hypertension pathogenesis. This knowledge could help to find novel therapeutic options and improve prognosis in this devastating disease.     

Normal adaptation of pulmonary arterial intima to extrauterine life in the pig: ultrastructural studies

Adaptation of the pulmonary arterial intima was studied in injected lung specimens of 34 Large White pigs. Each type of pre- and intra-acinar artery was studied separately using transmission and scanning electron microscopy. Determination of the endothelial surface/volume ratio and volume densities of (1) endothelium and subendothelium, (2) endothelial cytoplasmic organelles and (3) subendothelial connective tissue elements yielded 6832 measurements which comprised a computerized database. At birth, endothelial cell morphology changed more rapidly and to a greater extent in peripheral than in proximal arteries. Endothelial surface/volume ratio increased (p less than 0.0001). Fetal surface projections, junctional interdigitations and overlap became less evident. Adaptational changes were complete in three weeks. Between three weeks and adulthood a reduction in endothelial surface/volume ratio suggested cell growth. In the subendothelium the volume density of collagen and basement membrane and elastin increased (p less than 0.001). The internal elastic lamina, immature in all arteries at birth increased in thickness and integrity until in the adult, only in small muscular arteries did gaps between elastin profiles ensure frequent contact between endothelial and smooth muscle cells. At all ages regional differences in endothelial cell morphology were evident.     

Efficacy of artificial ventilation in oil microembolism and subsequent pulmonary edema

Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences. Department of Human and Animal Physiology, M. V. Lomonosov Moscow State University (Presented by Academician of the Russian Academy of Medical Sciences G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 7, pp. 18–19, July, 1992.     

慢性支气管炎、肺气肿时肺动脉高压与肺血管壁改建与炎症的关系

目的：研究慢性支气管炎(慢支)、肺气肿气道及肺部炎症在肺动脉重塑中的作用。方法:24只雄性Wistar大鼠分3组，每组8只；慢支、肺气肿4周组（A组）、慢支、肺气肿6周组（B组）、正常对照组（C组）。气管内注入脂多糖（LPS）和每天烟熏的混合刺激方法制作慢支、肺气肿动物模型。测定各组血气分析、肺血流动力学和肺泡灌洗液(BALF)细胞分类计数；观测气道、肺泡组织及肺血管的病理组织学改变。结果:（1）A、B组BALF细胞总数显著高于C组，细胞分类及气道壁浸润的细胞中，A组以中性粒细胞为主，B组以淋巴细胞、单核巨噬细胞为主，其气管、支气管及肺组织具有慢支、肺气肿的病理特征。（2）A、B组右心室收缩压（RVSP）、平均肺动脉压（mPAP）、右心室与左心室＋室间隔重量比（RV/LV+S）高于C组（P<0.05）。A、B肌化型动脉（MA）数量比亦高于C组(P<0.05)。（3）A、B组MA百分比、mPAP与平均肺泡面积,BALF细胞总数和中性粒细胞、淋巴细胞、单核巨噬细胞对小气道浸润程度呈正相关，与PaO2无相关性。在A组中，MA百分比、mPAP与BALF细胞数的中性粒细胞百分比呈正相关，而在B组中，与淋巴细胞百分比、单核巨噬细胞百分比呈正相关 。结论：（1）慢支、肺气肿在无低氧血症时已出现肺动脉高压、右心室肥厚及肺动脉重塑，其发生机制与气道及肺部的炎症浸润及炎症破坏程度相关。（2）此阶段肺动脉重塑改变以肺小动脉肌化为主要特点，并与肺血流动力学改变呈正相关。     

Gax在肺动脉高压大鼠肺动脉中的表达变化

目的:使用低氧及野百合碱(monocrotaline,MCT)诱导的两种肺动脉高压(pulmonary arterialhypertension,PAH)大鼠模型,观察生长终止特异性同源盒(growth arrest-specific homeobox,Gax)在肺动脉的表达变化。方法:Sprague Dawley大鼠随机分为四组:低氧模型组(n=16)、低氧对照组(n=16)、MCT模型组(n=16)及MCT对照组(n=16)。采用插管法测定大鼠的右心室压力及肺动脉压力。右心室质量除以左心室和室间隔质量,计算右心肥厚指数。采用定量RT-PCR法测定肺动脉主干及肺组织Gax mRNA表达;采用Western免疫印迹法测定肺动脉主干Gax蛋白表达;免疫组织化学染色观测Gax在肺内的分布及表达变化。结果:低氧模型组及MCT模型组大鼠的右心压力、肺动脉压力及右心肥厚指数均显著高于相应对照组(P<0.01),两种模型大鼠的肺动脉血管均出现明显重构。与对照组比较,Gax mRNA在两种模型组大鼠的肺组织表达降低(P<0.05),而在肺动脉主干表达升高(P<0.05)。Gax蛋白在肺内主要表达在微小动脉。与对照组比较,两种模型组大鼠的肺动脉主干和肺微小动脉Gax蛋白表达均升高(P<0.05),而肺组织Gax蛋白表达下降(P<0.05)。结论:Gax主要表达在肺微小动脉,在PAH发生时表达上调。     

An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.     

Histopathology of pulmonary hypertensive diseases

The spectrum of histopathological lesions of pulmonary hypertensive vascular disease is extraordinarily varied. A number of distinct patterns can be recognized, and these correlate with aetiological factors and clinical data. Recent research has yielded important new insights on the pathogenesis of pulmonary hypertension at the molecular and cellular level, and various key mechanisms are emerging. These include induction and maintenance of vasoconstriction, endothelial activation and proliferation, and thrombosis. In the light of these developments, a re-evaluation of lesions at the histopathological level is receiving a new level of significance, as histological data complement those from research based on non-morphological techniques. We review the main histopathological features of hypertensive pulmonary vascular disease in this perspective.     

Inhalation of Stachybotrys chartarum causes pulmonary arterial hypertension in mice

Inhalation of Stachybotrys chartarum, a ubiquitous fungus in our living environment, has been suspected as a cause of acute idiopathic pulmonary haemorrhage in infants, but its relation to human diseases is not yet known. The aim of present study was to investigate the effect of repeated intratracheal injection of the fungus into mice, paying special attention to the pulmonary vascular system. Spores of S. chartarum were injected into the trachea of mice from 6 to 18 times over 4-12 weeks, and the lungs were examined by histopathology, morphometrics and haemodynamics. When 1 x 10(4) spores/mouse were injected, histopathological examination showed the development of pulmonary arterial hypertension (PAH). Symmetrical thickening of the intima and media of the pulmonary arterial walls was seen after six injections over 4 weeks. Right ventricular hypertrophy was also evident after 12 injections. PAH was confirmed by the elevation of right ventricular systolic pressure (20.1 +/- 5.7 mmHg in the injected group vs. 12.0 +/- 2.4 mmHg in the control group, P < 0.01). This study showed that the inhalation of S. chartarum caused PAH in mice, suggesting a potential of S. chartarum as a cause of human health problem such as PAH.     

Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases

Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. We therefore hypothesized that pulmonary arterial hypertension associated with connective tissue diseases may be associated with obstructive lesions of pulmonary veins. Lung samples from 8 patients with pulmonary arterial hypertension associated with connective tissue disease (4 limited systemic sclerosis, 2 systemic lupus erythematosus, 1 mixed connective tissue diseases, and 1 rheumatoid arthritis) were studied by light microscopy and analyzed by immunohistochemistry (5 postmortem samples, 3 explants after lung transplantation). Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.     

Bilateral extensive cerebral infarction and mesenteric ischemia associated with segmental arterial mediolysis in two young women

Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic non-inflammatory vascular disease that affects mainly muscular arteries of the splanchnic and cerebral territories. Reported herein are two cases of SAM in young women with fatal outcome. One of the patients had an atypical form of the disease, which primarily affected small intestinal submucosal and subserosal arteries, and resulted in acute mesenteric ischemia. The other had bilateral brain infarction with SAM of internal carotid arteries (ICA). Pathological examination of both cases did not reveal the cause of blood flow disturbance: large mesenteric branches of the former and ICA of the latter were free of either dissection or thrombosis; in addition, small intestinal arteries of the first patient did not show signs of vasculitis. These findings suggest that unusual pathways of arterial occlusion and dissection may occur in the context of SAM.