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Sample records for pulmonary vascular trees

  1. Robust method for extracting the pulmonary vascular trees from 3D MDCT images

    Science.gov (United States)

    Taeprasartsit, Pinyo; Higgins, William E.

    2011-03-01

    Segmentation of pulmonary blood vessels from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. This work presents a method for extracting the vascular trees of the pulmonary arteries and veins, applicable to both contrast-enhanced and unenhanced 3D MDCT image data. The method finds 2D elliptical cross-sections and evaluates agreement of these cross-sections in consecutive slices to find likely cross-sections. It next employs morphological multiscale analysis to separate vessels from adjoining airway walls. The method then tracks the center of the likely cross-sections to connect them to the pulmonary vessels in the mediastinum and forms connected vascular trees spanning both lungs. A ground-truth study indicates that the method was able to detect on the order of 98% of the vessel branches having diameter >= 3.0 mm. The extracted vascular trees can be utilized for the guidance of safe bronchoscopic biopsy.

  2. Three-Dimensions Segmentation of Pulmonary Vascular Trees for Low Dose CT Scans

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    Lai, Jun; Huang, Ying; Wang, Ying; Wang, Jun

    2016-12-01

    Due to the low contrast and the partial volume effects, providing an accurate and in vivo analysis for pulmonary vascular trees from low dose CT scans is a challenging task. This paper proposes an automatic integration segmentation approach for the vascular trees in low dose CT scans. It consists of the following steps: firstly, lung volumes are acquired by the knowledge based method from the CT scans, and then the data are smoothed by the 3D Gaussian filter; secondly, two or three seeds are gotten by the adaptive 2D segmentation and the maximum area selecting from different position scans; thirdly, each seed as the start voxel is inputted for a quick multi-seeds 3D region growing to get vascular trees; finally, the trees are refined by the smooth filter. Through skeleton analyzing for the vascular trees, the results show that the proposed method can provide much better and lower level vascular branches.

  3. Pulmonary Vascular Tree Segmentation from Contrast-Enhanced CT Images

    CERN Document Server

    Helmberger, M; Pienn, M; Balint, Z; Olschewski, A; Bischof, H

    2013-01-01

    We present a pulmonary vessel segmentation algorithm, which is fast, fully automatic and robust. It uses a coarse segmentation of the airway tree and a left and right lung labeled volume to restrict a vessel enhancement filter, based on an offset medialness function, to the lungs. We show the application of our algorithm on contrast-enhanced CT images, where we derive a clinical parameter to detect pulmonary hypertension (PH) in patients. Results on a dataset of 24 patients show that quantitative indices derived from the segmentation are applicable to distinguish patients with and without PH. Further work-in-progress results are shown on the VESSEL12 challenge dataset, which is composed of non-contrast-enhanced scans, where we range in the midfield of participating contestants.

  4. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  5. Pulmonary manifestations of the collagen vascular diseases.

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    Wiedemann, H P; Matthay, R A

    1989-12-01

    The collagen vascular diseases are a heterogeneous group of immunologically mediated inflammatory disorders. The organs and tissues that compose the respiratory system are frequently affected by these diseases. Potential targets of the inflammation and injury include the lung parenchyma, tracheobronchial tree, pulmonary vasculature, pleura, larynx, and respiratory muscles. In this article, the spectrum of respiratory disease caused by systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, ankylosing spondylitis, relapsing polychondritis, and Sjögren's syndrome is reviewed. Where appropriate, therapeutic options are discussed.

  6. Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease.

    Directory of Open Access Journals (Sweden)

    Mariana Muñoz-Esquerre

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1 COPD, 2 smokers, and 3 non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1 percentage of intimal area (%IA, 2 percentage of luminal narrowing, 3 intimal thickness index, and 4 intima-to-media ratio.In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038. In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016. Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008.Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.

  7. Monitoring pulmonary vascular permeability using radiolabeled transferrin

    Energy Technology Data Exchange (ETDEWEB)

    Basran, G.S.; Hardy, J.G.

    1988-07-01

    A simple, noninvasive technique for monitoring pulmonary vascular permeability in patients in critical care units is discussed. High vascular permeability is observed in patients with clinically defined adult respiratory distress syndrome (ARDS) but not in patients with hydrostatic pulmonary edema or in patients with minor pulmonary insults who are considered to be at risk of developing ARDS. The technique has been used in the field of therapeutics and pharmacology to test the effects of the putative antipermeability agents methylprednisolone and terbutaline sulfate. There appears to be a good correlation between the acute inhibitory effect of either drug on transferrin exudation and patient prognosis. Thus, a byproduct of such drug studies may be an index of survival in patients with established ARDS.

  8. Retinal vascular tree reconstruction with anatomical realism.

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    Lin, Kai-Shun; Tsai, Chia-Ling; Tsai, Chih-Hsiangng; Sofka, Michal; Chen, Shih-Jen; Lin, Wei-Yang

    2012-12-01

    Motivated by the goals of automatically extracting vessel segments and constructing retinal vascular trees with anatomical realism, this paper presents and analyses an algorithm that combines vessel segmentation and grouping of the extracted vessel segments. The proposed method aims to restore the topology of the vascular trees with anatomical realism for clinical studies and diagnosis of retinal vascular diseases, which manifest abnormalities in either venous and/or arterial vascular systems. Vessel segments are grouped using extended Kalman filter which takes into account continuities in curvature, width, and intensity changes at the bifurcation or crossover point. At a junction, the proposed method applies the minimum-cost matching algorithm to resolve the conflict in grouping due to error in tracing. The system was trained with 20 images from the DRIVE dataset, and tested using the remaining 20 images. The dataset contained a mixture of normal and pathological images. In addition, six pathological fluorescein angiogram sequences were also included in this study. The results were compared against the groundtruth images provided by a physician, achieving average success rates of 88.79% and 90.09%, respectively.

  9. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progeni

  10. Echocardiographic assessment of pulmonary vascular resistance in pulmonary arterial hypertension

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    Bergot Emmanuel

    2010-06-01

    Full Text Available Abstract Background Echocardiographic ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract time-velocity integral (TRV/TVI rvot was presented as a reliable non-invasive method of estimating pulmonary vascular resistance (PVR. Studies using this technique in patients with moderate to high PVR are scarce. Left ventricular outflow tract time-velocity integral (TVI lvot can be easier to measure than TVI rvot, especially in patients with severe pulmonary hypertension (PH with significant anatomical modifications of the right structures. Aims We wanted to determine whether the TRV/TVI rvot and TRV/TVI lvot ratios would form a reliable non-invasive tool to estimate PVR in a cohort of patients with moderate to severe pulmonary vascular disease. Methods Doppler echocardiographic examination and right heart catheterisation were performed in 37 patients. Invasive PVR was compared with TRV/TVI rvot and TRV/TVI lvot ratios using regression analysis. Two equations were modelled and the results compared with invasive measurements using the Bland-Altman analysis. Using receiver-operating characteristics curve analysis, a cut-off value for the two ratios was generated. Results Correlation coefficients between invasive PVR and TRV/TVI rvot then TRV/TVI lvot were respectively 0.76 and 0.74. Two new equations were found but the Bland-Altman analysis showed wide standard deviations (respectively 3.8 and 3.9 Wood units. A TRV/TVI rvot then TRV/TVI lvot ratio cut-off value of 0.14 had a sensitivity of 93% and a specificity of 57% for the first and a sensitivity of 87% and a specificity of 57% for the second to determine PVR > 2 Wood units. Conclusion Echocardiography is useful for the screening of patients with pulmonary hypertension and PVR > 2 WU. It remains disappointing for accurate assessment of high PVR. TVI lvot may be an alternative to TVI rvot for patients for whom accurate TVI rvot measurement is not possible.

  11. Traversing and labeling interconnected vascular tree structures from 3D medical images

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    O'Dell, Walter G.; Govindarajan, Sindhuja Tirumalai; Salgia, Ankit; Hegde, Satyanarayan; Prabhakaran, Sreekala; Finol, Ender A.; White, R. James

    2014-03-01

    Purpose: Detailed characterization of pulmonary vascular anatomy has important applications for the diagnosis and management of a variety of vascular diseases. Prior efforts have emphasized using vessel segmentation to gather information on the number or branches, number of bifurcations, and branch length and volume, but accurate traversal of the vessel tree to identify and repair erroneous interconnections between adjacent branches and neighboring tree structures has not been carefully considered. In this study, we endeavor to develop and implement a successful approach to distinguishing and characterizing individual vascular trees from among a complex intermingling of trees. Methods: We developed strategies and parameters in which the algorithm identifies and repairs false branch inter-tree and intra-tree connections to traverse complicated vessel trees. A series of two-dimensional (2D) virtual datasets with a variety of interconnections were constructed for development, testing, and validation. To demonstrate the approach, a series of real 3D computed tomography (CT) lung datasets were obtained, including that of an anthropomorphic chest phantom; an adult human chest CT; a pediatric patient chest CT; and a micro-CT of an excised rat lung preparation. Results: Our method was correct in all 2D virtual test datasets. For each real 3D CT dataset, the resulting simulated vessel tree structures faithfully depicted the vessel tree structures that were originally extracted from the corresponding lung CT scans. Conclusion: We have developed a comprehensive strategy for traversing and labeling interconnected vascular trees and successfully implemented its application to pulmonary vessels observed using 3D CT images of the chest.

  12. CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls.

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    Taslakian, Bedros; Latson, Larry A; Truong, Mylene T; Aaltonen, Eric; Shiau, Maria C; Girvin, Francis; Alpert, Jeffrey B; Wickstrom, Maj; Ko, Jane P

    2016-11-01

    Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

  13. Multi-level tree analysis of pulmonary artery/vein trees in non-contrast CT images

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    Gao, Zhiyun; Grout, Randall W.; Hoffman, Eric A.; Saha, Punam K.

    2012-02-01

    Diseases like pulmonary embolism and pulmonary hypertension are associated with vascular dystrophy. Identifying such pulmonary artery/vein (A/V) tree dystrophy in terms of quantitative measures via CT imaging significantly facilitates early detection of disease or a treatment monitoring process. A tree structure, consisting of nodes and connected arcs, linked to the volumetric representation allows multi-level geometric and volumetric analysis of A/V trees. Here, a new theory and method is presented to generate multi-level A/V tree representation of volumetric data and to compute quantitative measures of A/V tree geometry and topology at various tree hierarchies. The new method is primarily designed on arc skeleton computation followed by a tree construction based topologic and geometric analysis of the skeleton. The method starts with a volumetric A/V representation as input and generates its topologic and multi-level volumetric tree representations long with different multi-level morphometric measures. A new recursive merging and pruning algorithms are introduced to detect bad junctions and noisy branches often associated with digital geometric and topologic analysis. Also, a new notion of shortest axial path is introduced to improve the skeletal arc joining two junctions. The accuracy of the multi-level tree analysis algorithm has been evaluated using computer generated phantoms and pulmonary CT images of a pig vessel cast phantom while the reproducibility of method is evaluated using multi-user A/V separation of in vivo contrast-enhanced CT images of a pig lung at different respiratory volumes.

  14. Effects of erythropoietin on advanced pulmonary vascular remodelling

    NARCIS (Netherlands)

    van Albada, M. E.; Sarvaas, G. J. du Marchie; Koster, J.; Houwertjes, M. C.; Berger, R. M. F.; Schoemaker, R. G.

    2008-01-01

    Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult ma

  15. Pulmonary vascular response of dogs with heartworm disease.

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    Rawlings, C A

    1978-10-01

    Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals.

  16. Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance.

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    Tobise, K; Tosaka, S; Onodera, S

    1992-05-01

    To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow.

  17. Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

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    Alaeddin B. Abukabda

    2017-05-01

    . Femoral artery response was reduced by 18 ± 5%, while third-order mesenteric arterioles were negatively affected by 20 µg nano-TiO2 with a mean decrease in response of 38.37 ± 10%. This is the first study to directly compare the differential effect of ENM exposure on discrete anatomical segments of the vascular tree. Pulmonary ENM exposure produced macrovascular and microvascular dysfunction resulting in impaired responses to endothelium-dependent, endothelium-independent, and adrenergic agonists with a more robust dysfunction at the microvascular level. These results provide additional evidence of an endothelium-dependent and endothelium-independent impairment in vascular reactivity.

  18. The effects of sufentanil in the feline pulmonary vascular bed.

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    Kaye, Alan D; Phelps, James; Baluch, Amir; Ibrahim, Ikhlass N; Hoover, Jason M; Baber, Syed R; Zhang, Cuihua; Armstrong, Christopher; Huffman, Shane; Fields, Aaron

    2006-03-18

    The purpose of this prospective vehicle controlled study was to test the hypothesis that sufentanil induces a depressor response in the pulmonary vascular bed of the cat and identify the receptors involved in the mediation or modulation of these effects. In separate experiments, the effects of diphenydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase (COX)-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to sufentanil and other agonists in the feline pulmonary vascular bed. The lobar arterial perfusion pressures were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, sufentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to sufentanil were significantly attenuated following administration of diphenhydramine and naloxone. The results of the present study suggest that sufentanil has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opioid receptor sensitive pathways.

  19. Pulmonary metastatic microangiopathy of colon cancer presenting as a "tree in bud" pattern.

    Science.gov (United States)

    Bosmans, S; Weynand, B; Coche, E

    2008-01-01

    The authors report an unusual case of a "tree in bud" pattern of vascular origin caused by colon cancer metastases. A 60-year-old man presented for routine follow-up of a colon tumour resected surgically 15 years previously. Clinical examination, laboratory tests, including carcino-embryonic antigen and inflammatory parameters, and chest radiograph were normal. Multislice CT of the lungs revealed the presence of several "tree in bud" opacities. The connection to the pulmonary arteries was well depicted by reformatted maximal intensity projection images. Biopsy of some of the nodules was characterized by mucinous material and neoplastic cells within the small vessels, consistent with metastases from the known colon adenocarcinoma.

  20. Dysfunction of pulmonary vascular endothelium in chronic obstructive pulmonary disease: basic considerations for future drug development.

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    Yang, Qin; Underwood, Malcolm J; Hsin, Michael K Y; Liu, Xiao-Cheng; He, Guo-Wei

    2008-09-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading health problems worldwide and continues to be a major cause of morbidity and mortality in developed countries. The clinical features of COPD are chronic obstructive bronchiolitis and emphysema. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD at different stages of the disease. Functional changes of pulmonary endothelial cells in COPD include antiplatelet abnormalities, anticoagulant disturbances, endothelial activation, atherogenesis, and compromised regulation of vascular tone which may adversely affect the ventilation-perfusion match in COPD. As the most important risk factor of COPD, cigarette smoking may initiate pulmonary vascular impairment through direct injury of endothelial cells or release of inflammatory mediators. Morphological changes such as denudation of endothelium and endothelial cell apoptosis have been observed in the pulmonary vasculature in COPD patients as well as functional alterations. Changes in the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin, selectins, and adhesion molecules in pulmonary endothelial cells as well as complex regulation and interaction of vasoactive substances and growth factors released from endothelium may underlie the mechanisms of pulmonary endothelial dysfunction in COPD. The mechanism of endothelial repair/regeneration in COPD, although not fully understood, may involve upregulation of vascular endothelial growth factors in the early stages along with an increased number of bone marrow-derived progenitor cells. These factors should be taken into account when developing new strategies for the pharmacological therapy of patients with COPD.

  1. Occlusion of pulmonary arteriovenous malformations by use of vascular plug

    DEFF Research Database (Denmark)

    Andersen, P E; Kjeldsen, A D

    2007-01-01

    Pulmonary arteriovenous malformations are commonly treated by embolization with coils or balloons to prevent cerebral complications and to raise the oxygenation of the blood. The Amplatzer vascular plug is a new occlusive device made of a self-expanding cylindrical nitinol mesh. It is fast and safe...

  2. Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension

    NARCIS (Netherlands)

    Bartelds, Beatrijs; van Loon, Rosa Laura E.; Mohaupt, Saffloer; Wijnberg, Hans; Dickinson, Michael G.; Takens, Janny; van Albada, Mirjam; Berger, Rolf M. F.; Boersma, B.

    2012-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive angioproliferative disease with high morbidity and mortality. Although the histopathology is well described, its pathogenesis is largely unknown. We previously identified the increased presence of mast cells and their markers in a ra

  3. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

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    Phan, Carole; Seferian, Andrei; Huertas, Alice; Thuillet, Raphaël; Sattler, Caroline; Le Hiress, Morane; Tamura, Yuichi; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Bouchet, Stéphane; Manéglier, Benjamin; Molimard, Mathieu; Rousselot, Philippe; Sitbon, Olivier; Simonneau, Gérald; Montani, David; Humbert, Marc

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor. Furthermore, dasatinib treatment induced pulmonary endothelial cell apoptosis in a dose-dependent manner, while imatinib did not. Dasatinib treatment mediated endothelial cell dysfunction via increased production of ROS that was independent of Src family kinases. Consistent with these findings, we observed elevations in markers of endothelial dysfunction and vascular damage in the serum of CML patients who were treated with dasatinib, compared with CML patients treated with imatinib. Taken together, our findings indicate that dasatinib causes pulmonary vascular damage, induction of ER stress, and mitochondrial ROS production, which leads to increased susceptibility to PH development. PMID:27482885

  4. Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

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    Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

    2012-01-01

    Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

  5. Constructal Law of Vascular Trees for Facilitation of Flow

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    Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.

    2014-01-01

    Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures. PMID:25551617

  6. Bile pigments in pulmonary and vascular disease

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    Stefan W. Ryter

    2012-03-01

    Full Text Available The bile pigments, biliverdin and bilirubin, are endogenously-derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  7. Bile pigments in pulmonary and vascular disease.

    Science.gov (United States)

    Ryter, Stefan W

    2012-01-01

    The bile pigments, biliverdin, and bilirubin, are endogenously derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  8. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation.

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    Landsberg, Judd W; Yuan, Jason X-J

    2004-04-01

    Ca(2+) is a major trigger for pulmonary vasoconstriction and a stimulus for pulmonary vascular smooth muscle cell proliferation. The transient receptor potential cation channels participate in regulating intracellular Ca(2+) and thus vascular contractility and cell proliferation. Upregulation of genes encoding these channels is involved in the development of pulmonary hypertension.

  9. Pulmonary vascular response to digoxin in newborn lambs.

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    Milstein, J M; Goetzman, B W

    1984-01-01

    The effects of digoxin on pulmonary vascular resistance (PVR) were evaluated in normoxic (N) and hypoxic (H) newborn lambs with normal and elevated PVR, respectively. Lambs were anesthetized and instrumented to enable continuous measurement of mean pulmonary arterial pressure (PPA), mean left atrial pressure (PLA), mean pulmonary blood flow (Qp), and mean aortic pressure (PAO). Digoxin (10-20 micrograms/kg) was injected via central venous catheters in 11 N lambs and 4 H lambs. Under N conditions, baseline PVR was equal to 0.12 mm Hg/ml/min/kg, PPA was 33 mm Hg, PLA was 6 mm Hg, Qp was 235 ml/min/kg, and PAO was 69 mm Hg. Following digoxin, mean PVR increased by 24% (P less than 0.001) and PPA increased by 23% (P less than 0.001) for an average duration of 199 sec while QP increased by 5% (P less than 0.02) and PLA was constant suggesting a direct vasoconstrictive effect. Under H conditions, baseline PVR was equal to 0.26 mm Hg/ml/min/kg, PPA was 58 mm Hg, PLA was 4 mm Hg, Qp was 208 ml/min/kg, and PAo was 65 mm Hg. Following digoxin, mean PVR, Qp, PLA, and PAo did not change appreciably although PPA had a uniform increase of 5% (P less than 0.001). The blunted response may suggest that either the pulmonary vascular bed was maximally constricted or that digoxin and hypoxia share a common mechanism. In conclusion, digoxin has a direct pulmonary vasoconstrictor action in newborn lambs. Because of its short duration, this action probably should not alter the clinical use of this drug in newborn humans.

  10. Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension.

    Science.gov (United States)

    Roberts, D H; Lepore, J J; Maroo, A; Semigran, M J; Ginns, L C

    2001-11-01

    We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health Care Finance Administration guidelines for long-term oxygen therapy. From 1996 to 1999, 23 adult patients (mean +/- SEM age, 51 +/- 4 years) with pulmonary arterial hypertension without left-heart failure underwent cardiac catheterization in a university teaching hospital while breathing air and then 100% oxygen. Treatment with 100% oxygen increased arterial oxygen saturation (91 +/- 1% to 99 +/- 0.1%, p < 0.05) and PaO(2) (64 +/- 3 to 309 +/- 28 mm Hg, p < 0.05). Treatment with 100% oxygen also decreased mean pulmonary artery pressure (56 +/- 3 to 53 +/- 2 mm Hg, p < 0.05) and increased cardiac index (2.1 +/- 0.1 to 2.5 +/- 0.2 L/min/m(2), p < 0.05). Calculated mean pulmonary vascular resistance (PVR) decreased from 14.1 +/- 1.4 to 10.6 +/- 1.0 Wood units (p < 0.05). Vasodilatation with 100% oxygen occurred preferentially in the pulmonary circulation (PVR/systemic vascular resistance, 0.53 +/- 0.04 to 0.48 +/- 0.03; p < 0.05). The magnitude of the PVR response to oxygen therapy was correlated only with decreasing patient age (r = 0.45, p < 0.05). Treatment with 100% oxygen is a selective pulmonary vasodilator in patients with pulmonary hypertension, regardless of primary diagnosis, baseline oxygenation, or right ventricular function. Development of disease-specific oxygen prescription guidelines warrants consideration.

  11. Tree mortality predicted from drought-induced vascular damage

    Science.gov (United States)

    Anderegg, William R. L.; Flint, Alan L.; Huang, Cho-ying; Flint, Lorraine E.; Berry, Joseph A.; Davis, Frank W.; Sperry, John S.; Field, Christopher B.

    2015-01-01

    The projected responses of forest ecosystems to warming and drying associated with twenty-first-century climate change vary widely from resiliency to widespread tree mortality1, 2, 3. Current vegetation models lack the ability to account for mortality of overstorey trees during extreme drought owing to uncertainties in mechanisms and thresholds causing mortality4, 5. Here we assess the causes of tree mortality, using field measurements of branch hydraulic conductivity during ongoing mortality in Populus tremuloides in the southwestern United States and a detailed plant hydraulics model. We identify a lethal plant water stress threshold that corresponds with a loss of vascular transport capacity from air entry into the xylem. We then use this hydraulic-based threshold to simulate forest dieback during historical drought, and compare predictions against three independent mortality data sets. The hydraulic threshold predicted with 75% accuracy regional patterns of tree mortality as found in field plots and mortality maps derived from Landsat imagery. In a high-emissions scenario, climate models project that drought stress will exceed the observed mortality threshold in the southwestern United States by the 2050s. Our approach provides a powerful and tractable way of incorporating tree mortality into vegetation models to resolve uncertainty over the fate of forest ecosystems in a changing climate.

  12. Cardiac catheterization in children with pulmonary hypertensive vascular disease.

    Science.gov (United States)

    Bobhate, Prashant; Guo, Long; Jain, Shreepal; Haugen, Richard; Coe, James Y; Cave, Dominic; Rutledge, Jennifer; Adatia, Ian

    2015-04-01

    The risks associated with cardiac catheterization in children with pulmonary hypertension (PH) are increased compared with adults. We reviewed retrospectively all clinical data in children with PH [mean pulmonary artery pressure (mean PAp) ≥25 mmHg and pulmonary vascular resistance index (PVRI) ≥3 Wood units m(2)] undergoing cardiac catheterization between 2009 and 2014. Our strategy included a team approach, minimal catheter manipulation and sildenafil administration prior to extubation. Adverse events occurring within 48 h were noted. Seventy-five patients (36 males), median age 4 years (0.3-17) and median weight 14.6 kg (2.6-77 kg), underwent 97 cardiac catheterizations. Diagnoses included idiopathic or heritable pulmonary arterial hypertension (PAH) (29 %), PAH associated with congenital heart disease (52 %), left heart disease (5 %) and lung disease (14 %). Mean PAp was 43 ± 19 mmHg; mean PVRI was 9.7 ± 6 Wood units m(2). There were no deaths or serious arrhythmias. No patient required cardiac massage. Three patients who suffered adverse events had suprasystemic PAp (3/3), heritable PAH (2/3), decreased right ventricular function (3/3), and pulmonary artery capacitance index <1 ml/mmHg/m(2) (3/3) and were treatment naïve (3/3). No patient undergoing follow-up cardiac catheterization suffered a complication. In 45 % of cases, the data acquired from the follow-up cardiac catheterization resulted in an alteration of therapy. Three percent of children with PH undergoing cardiac catheterization suffered adverse events. However, there were no intra or post procedural deaths and no one required cardiac massage or cardioversion. Follow-up cardiac catheterization in patients receiving pulmonary hypertensive targeted therapy is safe and provides useful information.

  13. Pulmonary Vascular Capacitance as a Predictor of Vasoreactivity in Idiopathic Pulmonary Arterial Hypertension Tested by Adenosine

    Directory of Open Access Journals (Sweden)

    Shafie

    2015-09-01

    Full Text Available Background Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH. Pulmonary arteriolar capacitance (Cp approximated by stroke volume divided by pulmonary pulse pressure (SV/PP is considered as an independent predictor of mortality in patients with IPAH. Objectives We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested with adenosine. Patients and Methods Fourteen patients with IPAH and a vasoreactive adenosine vasoreactivity testing according to the ESC guidelines were compared with 24 IPAH patients with nonreactive adenosine test results. Results There were no statistical significant differences between the two groups regarding NYHA class, body surface area, heart rate, and systemic blood pressure during right heart catheterization. Hemodynamic study showed no statistical significant differences in cardiac output/Index, mean pulmonary artery pressure, pulmonary vascular resistance, and baseline Cp between the two groups. There was a statistical significant but weak increase in adenosine Cp in vasoreactive group compared to non-reactive group (P = 0.04. Multivariable analysis showed an association between Cp and vasoreactivity (Beta = 2, P = 0.04, OR = 0.05 (95%CI = 0.003 - 0.9. Conclusions Cp could be considered as an index for the prediction of vasoreactivity in patients with IPAH. Prediction of long-term response to calcium channel blockers in patients with IPAH and a positive vasoreactive test by this index should be addressed in further studies.

  14. Endotoxin increases pulmonary vascular protein permeability in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, C.H.; Dauber, I.M.; Weil, J.V.

    1986-10-01

    Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonella enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.

  15. Effect of L-Arginine on Pulmonary Artery Smooth Muscle Cell Apoptosis in Rats with Hypoxic Pulmonary Vascular Structural Remodeling

    Institute of Scientific and Technical Information of China (English)

    Ingrid Karmane SUMOU; Jun-Bao DU; Bing WEI; Chun-Yu ZHANG; Jian-Guang QI; Chao-Shu TANG

    2006-01-01

    This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatebiotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

  16. Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    A.R. Kranenburg (Andor); W.I. de Boer (Pim); J.H.J.M. van Krieken (Han); W.J. Mooi (Wolter); J.E. Walters (Jane); P.R. Saxena (Pramod Ranjan); P.J. Sterk (Peter); H.S. Sharma (Hari)

    2002-01-01

    textabstractImportant characteristics of chronic obstructive pulmonary disease (COPD) include airway and vascular remodeling, the molecular mechanisms of which are poorly understood. We assessed the role of fibroblast growth factors (FGF) in pulmonary vascular remodeling by examini

  17. Pulmonary manifestations in collagen vascular diseases; Pulmonale Manifestationen bei Kollagenosen

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, M.N.A. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kreuter, M. [Thoraxklinik, Universitaetsklinikum Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management. (orig.) [German] Pulmonale Komplikationen sind bei Patienten mit Kollagenosen keine Seltenheit. Haeufig sind eine direkte Manifestation der Grunderkrankung, eine Nebenwirkung der medikamentoesen Therapie oder eine Lungeninfektion die Ursachen. Das radiologische Standardverfahren zur Klaerung pulmonaler Pathologien bei Patienten mit Kollagenosen ist die Multidetektorcomputertomographie mit duennschichtigen Rekonstruktionen (Duennschicht-MDCT). Die Treffsicherheit der Duennschicht-MDCT ist fuer die Identifikation eines Erkrankungsmusters sehr hoch. So kann beispielsweise das Muster einer

  18. Generating patient-specific pulmonary vascular models for surgical planning

    Science.gov (United States)

    Murff, Daniel; Co-Vu, Jennifer; O'Dell, Walter G.

    2015-03-01

    Each year in the U.S., 7.4 million surgical procedures involving the major vessels are performed. Many of our patients require multiple surgeries, and many of the procedures include "surgical exploration". Procedures of this kind come with a significant amount of risk, carrying up to a 17.4% predicted mortality rate. This is especially concerning for our target population of pediatric patients with congenital abnormalities of the heart and major pulmonary vessels. This paper offers a novel approach to surgical planning which includes studying virtual and physical models of pulmonary vasculature of an individual patient before operation obtained from conventional 3D X-ray computed tomography (CT) scans of the chest. These models would provide clinicians with a non-invasive, intricately detailed representation of patient anatomy, and could reduce the need for invasive planning procedures such as exploratory surgery. Researchers involved in the AirPROM project have already demonstrated the utility of virtual and physical models in treatment planning of the airways of the chest. Clinicians have acknowledged the potential benefit from such a technology. A method for creating patient-derived physical models is demonstrated on pulmonary vasculature extracted from a CT scan with contrast of an adult human. Using a modified version of the NIH ImageJ program, a series of image processing functions are used to extract and mathematically reconstruct the vasculature tree structures of interest. An auto-generated STL file is sent to a 3D printer to create a physical model of the major pulmonary vasculature generated from 3D CT scans of patients.

  19. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

    Directory of Open Access Journals (Sweden)

    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  20. Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

    NARCIS (Netherlands)

    S.M.K. Shehata; W.J. Mooi (Wolter); T. Okazaki (Tadaharu); I. El-Banna; H.S. Sharma (Hari); D. Tibboel (Dick)

    1999-01-01

    textabstractBACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the mo

  1. Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

    Science.gov (United States)

    MOLTHEN, Robert C.; WU, Qingping; FISH, Brian L.; MOULDER, John E.; JACOBS, Elizabeth R.; MEDHORA, Meetha M.

    2013-01-01

    Background and objective A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Results Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Conclusions Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident. PMID:22882664

  2. Interaction network of vascular epiphytes and trees in a subtropical forest

    Science.gov (United States)

    Ceballos, Sergio Javier; Chacoff, Natacha Paola; Malizia, Agustina

    2016-11-01

    The commensalistic interaction between vascular epiphytes and host trees is a type of biotic interaction that has been recently analysed with a network approach. This approach is useful to describe the network structure with metrics such as nestedness, specialization and interaction evenness, which can be compared with other vascular epiphyte-host tree networks from different forests of the world. However, in several cases these comparisons showed different and inconsistent patterns between these networks, and their possible ecological and evolutionary determinants have been scarcely studied. In this study, the interactions between vascular epiphytes and host trees of a subtropical forest of sierra de San Javier (Tucuman, Argentina) were analysed with a network approach. We calculated metrics to characterize the network and we analysed factors such as the abundance of species, tree size, tree bark texture, and tree wood density in order to predict interaction frequencies and network structure. The interaction network analysed exhibited a nested structure, an even distribution of interactions, and low specialization, properties shared with other obligated vascular epiphyte-host tree networks with a different assemblage structure. Interaction frequencies were predicted by the abundance of species, tree size and tree bark texture. Species abundance and tree size also predicted nestedness. Abundance indicated that abundant species interact more frequently; and tree size was an important predictor, since larger-diameter trees hosted more vascular epiphyte species than small-diameter trees. This is one of the first studies analyzing interactions between vascular epiphytes and host trees using a network approach in a subtropical forest, and taking the whole vascular epiphyte assemblage of the sampled community into account.

  3. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  4. Plasticity of vascular progenitor cells: Implications in pulmonary vascular remodelling in COPD

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    M. Díez

    2006-12-01

    Full Text Available Vascular progenitor cells (VPC have shown in vitro and in vivo their ability to differentiate into endothelial cells (EC. Some evidence suggests that the plasticity of these cells to differentiate into other cell types might contribute not only to angiogenesis but also to perpetuate vascular lesions. Studies done in pulmonary arteries (PA of patients with COPD have demonstrated the presence of VPC infiltrating the intima. Since intimal thickening is mainly constituted by smooth muscle cells (SMC, we asked whether VPC could play a role in wall thickening. Accordingly, the objective was to evaluate in vitro the plasticity of VPC to differentiate into SMC and EC of human PA. G-CSF-mobilized peripheral blood CD133+ cells from a commercial primary line were expanded and labelled with acetylated-LDL-DiI for tracking cell purposes. Then, cells were co-cultured with commercial primary lines of human PA EC or SMC (n = 3. As control, CD133+ cells were cultured alone, with minimal medium with or without VEGF (50ng·ml–1. After 6 and 12 days of growth, the phenotype of cultures was characterized by immunofluorescence with: lectin, -actin and CD31. Cells were also evaluated morphologically. After 6 days, VPC acquired the morphology and the phenotype of the cells with which they were co-cultured, EC (lectin+, CD31+, alpha-actin- or SMC (alpha-actin+, lectin-, CD31-. VPC cultured 12 days alone or with VEGF did not acquire typical morphology and markers of mature EC or SMC of PA. We conclude that VPC have the potential to differentiate in vitro into SMC, and that this plasticity could contribute to perpetuate pulmonary vascular remodelling in COPD.

  5. 4D magnetic resonance flow imaging for estimating pulmonary vascular resistance in pulmonary hypertension.

    Science.gov (United States)

    Kheyfets, Vitaly O; Schafer, Michal; Podgorski, Chris A; Schroeder, Joyce D; Browning, James; Hertzberg, Jean; Buckner, J Kern; Hunter, Kendal S; Shandas, Robin; Fenster, Brett E

    2016-10-01

    To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity-encoded phase contract magnetic resonance imaging (here termed 4D MRI). In all, 17 patients with pulmonary hypertension (PH) and five controls underwent right heart catheterization (RHC), 4D and 2D Cine MRI (1.5T) within 24 hours. MRI was used to compute maximum spatial peak systolic vorticity in the main pulmonary artery (MPA) and right pulmonary artery (RPA), cardiac output, and relative area change in the MPA. These parameters were combined in a four-parameter multivariate linear regression model to arrive at an estimate of PVR. Agreement between model predicted and measured PVR was also evaluated using Bland-Altman plots. Finally, model accuracy was tested by randomly withholding a patient from regression analysis and using them to validate the multivariate equation. A decrease in vorticity in the MPA and RPA were correlated with an increase in PVR (MPA: R(2) = 0.54, P < 0.05; RPA: R(2) = 0.75, P < 0.05). Expanding on this finding, we identified a multivariate regression equation that accurately estimates PVR (R(2) = 0.94, P < 0.05) across severe PH and normotensive populations. Bland-Altman plots showed 95% of the differences between predicted and measured PVR to lie within 1.49 Wood units. Model accuracy testing revealed a prediction error of ∼20%. A multivariate model that includes MPA relative area change and flow characteristics, measured using 4D and 2D Cine MRI, offers a promising technique for noninvasively estimating PVR in PH patients. J. MAGN. RESON. IMAGING 2016;44:914-922. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-hui LI; Jun-bao DU; Ding-fang BU; Xiu-ying TANG; Chao-shu TANG

    2006-01-01

    Aim: To explore the possible role of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow. Methods: Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham+NaHS (a H2S donor) and shunt+NaHS groups. Rats in shunt and shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt+NaHS and sham+NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) activation were analyzed by Western blotting. Results: After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide (NO). However, lung tissue carbon monoxide (CO) did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats. Conclusions: H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.

  7. Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.

    Science.gov (United States)

    Talbot, Nick P; Croft, Quentin P; Curtis, M Kate; Turner, Brandon E; Dorrington, Keith L; Robbins, Peter A; Smith, Thomas G

    2014-12-01

    Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.

  8. Host tree phenology affects vascular epiphytes at the physiological, demographic and community level.

    Science.gov (United States)

    Einzmann, Helena J R; Beyschlag, Joachim; Hofhansl, Florian; Wanek, Wolfgang; Zotz, Gerhard

    2014-11-11

    The processes that govern diverse tropical plant communities have rarely been studied in life forms other than trees. Structurally dependent vascular epiphytes, a major part of tropical biodiversity, grow in a three-dimensional matrix defined by their hosts, but trees differ in their architecture, bark structure/chemistry and leaf phenology. We hypothesized that the resulting seasonal differences in microclimatic conditions in evergreen vs. deciduous trees would affect epiphytes at different levels, from organ physiology to community structure. We studied the influence of tree leaf phenology on vascular epiphytes on the Island of Barro Colorado, Panama. Five tree species were selected, which were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous trees, characterized by sunnier and drier microclimates, hosted fewer individuals and less diverse epiphyte assemblages. Differences were also observed at a functional level, e.g. epiphyte assemblages in deciduous trees had larger proportions of Crassulacean acid metabolism species and individuals. At the population level a drier microclimate was associated with lower individual growth and survival in a xerophytic fern. Some species also showed, as expected, lower specific leaf area and higher δ(13)C values when growing in deciduous trees compared with evergreen trees. As hypothesized, host tree leaf phenology influences vascular epiphytes at different levels. Our results suggest a cascading effect of tree composition and associated differences in tree phenology on the diversity and functioning of epiphyte communities in tropical lowland forests.

  9. Rate of angiotensin II generation within the human pulmonary vascular bed

    DEFF Research Database (Denmark)

    Giese, Jacob; Kappelgaard, A M; Tønnesen, K H

    1980-01-01

    Plasma angiotensin II concentration gradients across the pulmonary vascular bed were measured during diagnostic renal venous/right heart catheterization in twenty-seven hypertensive patients with renal or renovascular disease. There was a linear correlation between the plasma angiotensin II...... vascular bed varied from 0.7 to 1.71/min, i.e. within a fairly narrow range....

  10. Meandering right pulmonary vein associated with severe and progressive "idiopathic-like" pulmonary hypertensive vascular disease.

    Science.gov (United States)

    Cuenca, Sofia; Bret, Montserrat; del Cerro, Maria Jesus

    2016-03-01

    Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure.

  11. Pulmonary exposure to carbon black nanoparticles and vascular effects

    Directory of Open Access Journals (Sweden)

    Wallin Håkan

    2010-11-01

    Full Text Available Abstract Background Exposure to small size particulates is regarded as a risk factor for cardiovascular diseases. Methods We exposed young and aged apolipoprotein E knockout mice (apoE-/- to carbon black (Printex 90, 14 nm by intratracheal instillation, with different dosing and timing, and measured vasomotor function, progression of atherosclerotic plaques, and VCAM-1, ICAM-1, and 3-nitrotyrosine in blood vessels. The mRNA expression of VCAM-1, ICAM-1, HO-1, and MCP-1 was examined in lung tissue. Results Young apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black exhibited lower acetylcholine-induced vasorelaxation in aorta segments mounted in myographs, whereas single doses of 0.05-2.7 mg/kg produced no such effects. The phenylephrine-dependent vasocontraction response was shifted toward a lower responsiveness in the mice exposed once to a low dose for 24 hours. No effects were seen on the progression of atherosclerotic plaques in the aged apoE-/- mice or on the expression of VCAM-1 and ICAM-1 and the presence of 3-nitrotyrosine in the vascular tissue of either young or aged apoE-/- mice. The expression of MCP-1 mRNA was increased in the lungs of young apoE-/- mice exposed to 0.9-2.7 mg/kg carbon black for 24 hours and of aged apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black seven and five weeks prior to sacrifice. Conclusion Exposure to nano-sized carbon black particles is associated with modest vasomotor impairment, which is associated neither with nitrosative stress nor with any obvious increases in the expression of cell adhesion proteins on endothelial cells or in plaque progression. Evidence of pulmonary inflammation was observed, but only in animals exposed to higher doses.

  12. Pulmonary alveolar microlithiasis with cor pulmonale: an autopsy case demonstrating a marked decrease in pulmonary vascular beds.

    Science.gov (United States)

    Terada, Tadashi

    2009-11-01

    Pulmonary alveolar microlithiasis (PAM) is a very rare autosomal recessive disorder in which microliths are formed in the alveolar space. PAM is infrequently complicated by pulmonary hypertension, the cause of which is unclear. The author in this paper found that the pulmonary hypertension was caused by a marked decrease in pulmonary vascular beds. Here, an autopsy case of PAM with a marked cor pulmonale is reported. A 14-year-old woman was found to have an abnormal pulmonary shadow, but the cause was unclear. At 24 years, she was diagnosed with a diffuse pulmonary abnormal shadow. At 42 years, she was diagnosed with PAM by imaging techniques. Her condition gradually worsened and she had to be treated with oxygen. She died of respiratory failure at 54 years. An autopsy revealed severe PAM and marked cor pulmonale. The heart weighed 360 g and right ventricular thickness was 10 mm (normal, 2-3 mm). Microscopically, the alveolar space was diffusely filled with microliths, and heart failure cells were recognized. Bone formations were scattered. The alveolar walls showed fibrous thickening, and pulmonary arteries showed atherosclerosis. The right ventricle showed marked cardiac hypertrophy. Chronic severe liver congestion was noted. A morphometric analysis using CD34-stained specimens showed a marked decrease (one tenth) in pulmonary capillary beds (capillary number: 8.6 +/- 3.1 per image), compared with normal lungs obtained from two other autopsies (85.3 +/- 9.4 and 96.2 +/- 10,3). It was concluded that the cor pulmonale and pulmonary hypertension in the present case were caused by the marked decrease of the pulmonary arterial vascular beds. More research is required regarding the etiology and treatment of PAM.

  13. Pulmonary vascular complications in portal hypertension and liver disease: A concise review

    Directory of Open Access Journals (Sweden)

    M. Porres-Aguilar

    2013-01-01

    Full Text Available Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.

  14. Hemodynamic evidence of vascular remodeling in combined post- and precapillary pulmonary hypertension

    Science.gov (United States)

    Brittain, Evan L.; Wells, Quinn S.; Farber-Eger, Eric H.; Halliday, Stephen J.; Doss, Laura N.; Xu, Meng; Wang, Li; Harrell, Frank E.; Yu, Chang; Robbins, Ivan M.; Newman, John H.; Hemnes, Anna R.

    2016-01-01

    Abstract Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH. PMID:27683608

  15. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension

    Science.gov (United States)

    Bertero, Thomas; Oldham, William M.; Cottrill, Katherine A.; Pisano, Sabrina; Vanderpool, Rebecca R.; Yu, Qiujun; Zhao, Jingsi; Tai, Yiyin; Tang, Ying; Zhang, Ying-Yi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi; Gorcsan, John; Vargas, Sara O.; Saggar, Rajan; Saggar, Rajeev; Wallace, W. Dean; Ross, David J.; Haley, Kathleen J.; Parikh, Victoria N.; De Marco, Teresa; Hsue, Priscilla Y.; Morris, Alison; Simon, Marc A.; Norris, Karen A.; Gaggioli, Cedric; Loscalzo, Joseph; Fessel, Joshua; Chan, Stephen Y.

    2016-01-01

    Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus–infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ–GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH. PMID:27548520

  16. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  17. Lung biopsy diagnosis of operative indication in secundum atrial septal defect with severe pulmonary vascular disease.

    Science.gov (United States)

    Yamaki, Shigeo; Kumate, Munetaka; Yonesaka, Susumu; Maeda, Katsuhide; Endo, Masato; Tabayashi, Koichi

    2004-10-01

    Surgical indication was determined by lung biopsy in 91 patients with secundum atrial septal defect (ASD) and severe pulmonary hypertension > 70 mm Hg of pulmonary arterial peak pressure and/or pulmonary vascular resistance of > 8 U/m(2). Pulmonary vascular disease (PVD) in ASD was classified into four types: (1) Musculoelastosis consisting of longitudinal muscle bundles and elastic fibers; surgery is indicated no matter how severely the peripheral small pulmonary arteries are occluded. Surgery was performed in all of the 20 patients, and the postoperative course was uneventful. (2) Plexogenic pulmonary arteriopathy: surgery is indicated for a PVD index < or = 2.3. Surgery was performed in 25 of the 32 patients. The remaining seven patients for whom surgery was not indicated are under follow-up observation. No deaths have occurred among the 32 patients. (3) Thromboembolism of small pulmonary arteries: Surgery is indicated for all such cases. Surgery was indicated in all of the five patients. (4) Mixed type of plexogenic pulmonary arteriopathy and musculoelastosis: Surgery is indicated if the collateral is not observed. Surgery was performed in 15 of the 25 patients. The remaining 10 patients for whom surgery was not indicated are under follow-up observation. Nine of these 91 patients associated with primary pulmonary hypertension were eliminated from this study. No deaths due to PVD occurred among the 82 patients who underwent lung biopsy diagnosis. Lung biopsy diagnosis is concluded to be very effective.

  18. Role of platelets in maintenance of pulmonary vascular permeability to protein

    Energy Technology Data Exchange (ETDEWEB)

    Lo, S.K.; Burhop, K.E.; Kaplan, J.E.; Malik, A.B. (Albany Medical College of Union Univ., NY (USA))

    1988-04-01

    The authors examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Q{sub lym}). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (P{sub la}). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelia permeability of {sup 125}I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 {times} 10{sup 7} or 5 {times} 10{sup 7} platelets were added onto endothelial monolayers. However, addition of 5 {times} 10{sup 6} platelets or 5 {times} 10{sup 7} red blood cells did not reduce endothelial monolayer albumin permeability. Results indicate that platelets are required for the maintenance of pulmonary vascular permeability. Reduction in permeability appears to involve an interaction of platelets with the endothelium.

  19. Shape-based 3D vascular tree extraction for perforator flaps

    Science.gov (United States)

    Wen, Quan; Gao, Jean

    2005-04-01

    Perforator flaps have been increasingly used in the past few years for trauma and reconstructive surgical cases. With the thinned perforated flaps, greater survivability and decrease in donor site morbidity have been reported. Knowledge of the 3D vascular tree will provide insight information about the dissection region, vascular territory, and fascia levels. This paper presents a scheme of shape-based 3D vascular tree reconstruction of perforator flaps for plastic surgery planning, which overcomes the deficiencies of current existing shape-based interpolation methods by applying rotation and 3D repairing. The scheme has the ability to restore the broken parts of the perforator vascular tree by using a probability-based adaptive connection point search (PACPS) algorithm with minimum human intervention. The experimental results evaluated by both synthetic and 39 harvested cadaver perforator flaps show the promise and potential of proposed scheme for plastic surgery planning.

  20. Placental Vascular Tree as Biomarker of Autism/ASD Risk

    Science.gov (United States)

    2012-09-01

    U UU 31 19b. TELEPHONE NUMBER (include area code ) Award Number 10-1-0626 Table of Contents...the graph nodes from the labeled branch points and the graph edges based from the connecting vessel tracing lines, which also codes vascular...Bloomberg SPH , Baltimore MD, MIND Institute UC Davis, Sacramento CA, Kaiser Permanente, Oakland, CA. Hypothesis. We hypothesize that vascular

  1. Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.

    Science.gov (United States)

    Cordero-Schmidt, G; Wallenstein, M B; Ozen, M; Shah, N A; Jackson, E; Hovsepian, D M; Palma, J P

    2014-09-01

    Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.

  2. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

    Science.gov (United States)

    Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

    1999-12-01

    Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

  3. The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

    Directory of Open Access Journals (Sweden)

    Lili Li

    Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

  4. Fractal Dimension Analysis of MDCT Images for Quantifying the Morphological Changes of the Pulmonary Artery Tree in Patients with Pulmonary Hypertension

    OpenAIRE

    2011-01-01

    Objective The aim of this study was to use fractal dimension (FD) analysis on multidetector CT (MDCT) images for quantifying the morphological changes of the pulmonary artery tree in patients with pulmonary hypertension (PH). Materials and Methods Fourteen patients with PH and 17 patients without PH as controls were studied. All of the patients underwent contrast-enhanced helical CT and transthoracic echocardiography. The pulmonary artery trees were generated using post-processing software, a...

  5. Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests.

    Science.gov (United States)

    Su, Junjing; Manisty, Charlotte; Simonsen, Ulf; Howard, Luke S; Parker, Kim H; Hughes, Alun D

    2017-08-17

    Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear. Wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests. Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate. In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise. This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function. Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants

  6. Antagonism of Stem Cell Factor/c-kit Signaling Attenuates Neonatal Chronic Hypoxia-Induced Pulmonary Vascular Remodeling

    Science.gov (United States)

    Young, Karen C; Torres, Eneida; Hehre, Dorothy; Wu, Shu; Suguihara, Cleide; Hare, Joshua M.

    2015-01-01

    Background Accumulating evidence suggests that c-kit positive cells are present in the remodeled pulmonary vasculature bed of patients with pulmonary hypertension (PH). Whether stem cell factor (SCF)/ c-kit regulated pathways potentiate pulmonary vascular remodeling is unknown. Here, we tested the hypothesis that attenuated c-kit signaling would decrease chronic hypoxia-induced pulmonary vascular remodeling by decreasing pulmonary vascular cell mitogenesis. Methods Neonatal FVB/NJ mice treated with non-immune IgG (PL), or c-kit neutralizing antibody (ACK2) as well as c-kit mutant mice (WBB6F1- Kit W− v/ +) and their congenic controls, were exposed to normoxia (FiO2=0.21) or hypoxia (FiO2=0.12) for two weeks. Following this exposure, right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), pulmonary vascular cell proliferation and remodeling were evaluated. Results As compared to chronically hypoxic controls, c-kit mutant mice had decreased RVSP, RVH, pulmonary vascular remodeling and proliferation. Consistent with these findings, administration of ACK2 to neonatal mice with chronic hypoxia-induced PH decreased RVSP, RVH, pulmonary vascular cell proliferation and remodeling. This attenuation in PH was accompanied by decreased extracellular signal-regulated protein kinase (ERK) 1/2 activation. Conclusion SCF/c-kit signaling may potentiate chronic hypoxia-induced vascular remodeling by modulating ERK activation. Inhibition of c-kit activity may be a potential strategy to alleviate PH. PMID:26705118

  7. The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults

    Science.gov (United States)

    Wright, Stephen P.; Granton, John T.; Esfandiari, Sam; Goodman, Jack M.

    2016-01-01

    Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship.This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP.We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP.Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP.Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp‐time. The RpCp‐time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp‐time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non‐athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8–10 min stages of cycle ergometry, at targeted heart‐rates of 100 beats min–1 (Light) and 120 beats min–1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate

  8. Endovascular treatment of pulmonary sequestration in adults using Amplatzer® vascular plugs.

    Science.gov (United States)

    Leoncini, Giacomo; Rossi, Umberto G; Ferro, Carlo; Chessa, Leonardo

    2011-01-01

    Two adult patients were diagnosed with extralobar and intralobar pulmonary sequestration. One patient presented with haemoptysis. Both patients suffered from recurrent episodes of severe pulmonary infections. Both patients were treated by means of endovascular embolization using Amplatzer(®) vascular plugs (AVPs). They were discharged from hospital after 48 and 24 h and then followed up for 24 and six months, respectively. No recurrence of symptoms was observed. Computed tomography scans were obtained every six months. Persistent occlusion of vascular supply and moderate regression of the sequestered lung tissue are evident after 24 and six months in both patients. Just one case of an adult patient affected by pulmonary sequestration and treated by endovascular embolization has been reported to date. The present report is the first on the use of the AVPs in adults for this condition. The potential advantages and drawbacks of this treatment modality in adults are discussed, as well the specific benefit represented by the AVPs.

  9. Comparison of the effect of inhaled anaesthetic with intravenous anaesthetic on pulmonary vascular resistance measurement during cardiac catheterisation.

    Science.gov (United States)

    Giesen, Leonie A; White, Michelle; Tulloh, Robert M R

    2015-02-01

    Children with pulmonary hypertension routinely undergo pulmonary vascular resistance studies to assess the disease severity and vasodilator responsiveness. It is vital that results are accurate and reliable and are not influenced by the choice of anaesthetic agent. However, there are anecdotal data to suggest that propofol and inhalational agents have different effects on pulmonary vascular resistance. A total of 10 children with pulmonary hypertension were selected sequentially to be included in the study. To avoid confounding because of baseline anatomic or demographic details, a crossover protocol was implemented, using propofol or isoflurane, with time for washout in between each agent and blinding of the interventionalist. Pulmonary and systemic vascular resistance were not significantly different when using propofol or isoflurane. However, the calculated resistance fraction - ratio of pulmonary resistance to systemic resistance - was significantly lower when using propofol than when using isoflurane. Although no difference in pulmonary vascular resistance was demonstrated, this pilot study suggests that the choice of anaesthetic agent may affect the calculation of relative pulmonary and systemic vascular resistance, and provides some preliminary evidence to favour propofol over isoflurane. These findings require replication in a larger study, and thus they should be considered in future calculations to make informed decisions about the management of children with pulmonary hypertension.

  10. Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation.

    Science.gov (United States)

    Barman, S A; Senteno, E; Smith, S; Taylor, A E

    1989-10-01

    Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.

  11. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  12. Vascular Tree Segmentation in Medical Images Using Hessian-Based Multiscale Filtering and Level Set Method

    Directory of Open Access Journals (Sweden)

    Jiaoying Jin

    2013-01-01

    extraction of vascular trees from 2D medical images is presented, which combines Hessian-based multiscale filtering and a modified level set method. In the proposed algorithm, the morphological top-hat transformation is firstly adopted to attenuate background. Then Hessian-based multiscale filtering is used to enhance vascular structures by combining Hessian matrix with Gaussian convolution to tune the filtering response to the specific scales. Because Gaussian convolution tends to blur vessel boundaries, which makes scale selection inaccurate, an improved level set method is finally proposed to extract vascular structures by introducing an external constrained term related to the standard deviation of Gaussian function into the traditional level set. Our approach was tested on synthetic images with vascular-like structures and 2D slices extracted from real 3D abdomen magnetic resonance angiography (MRA images along the coronal plane. The segmentation rates for synthetic images are above 95%. The results for MRA images demonstrate that the proposed method can extract most of the vascular structures successfully and accurately in visualization. Therefore, the proposed method is effective for the vascular tree extraction in medical images.

  13. VASOACTIVE INTESTINAL POLYPEPTIDE PREVENTS INJURY OF PULMONARY VASCULAR PERMEABILITY DUE TO XANTHINE WITH XANTHINE OXIDASE

    Institute of Scientific and Technical Information of China (English)

    林耀广

    1995-01-01

    Hyperpermeability is a crux of pathogenesis of sudden lung edema in many pulmooary disorders,espe=cially in acute lung injury and adult respiratory distress syndrome(ARDS). Using our modified method for assessment of pulmonary vascular permeability,we observed the effects of xanthine with xanthine oxi-dase (X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide (VIP) against the injury of pulmonary vascular permesbility.After addition of xanthine oxidase in the perfusate reservoir containing xanthine,125I-albumin leak index (125IALI) was remarkably increased while peak airway pressure (Paw) was not significantly increased,and perfusion pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only slightly increased.Xanthine plus xanthine oxi-dase also increased thromboxane B2(TX B2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) in the perfusat-e.Treatment with VIP obviously reduced or totally prevented all signs of injury.Simultaneously,VIP also diminished or abolished the associated generation of arachidonate products.The results indicated that VIP bas potent protective activity against injury of pulmonary vasculat permeability and may be a physiological modulator of inflammatory damage to vaseular eodothelium associated with toxic oxygen metabolites.

  14. Genetic Ablation of PDGF-Dependent Signaling Pathways Abolishes Vascular Remodeling and Experimental Pulmonary Hypertension.

    Science.gov (United States)

    Ten Freyhaus, Henrik; Berghausen, Eva M; Janssen, Wiebke; Leuchs, Maike; Zierden, Mario; Murmann, Kirsten; Klinke, Anna; Vantler, Marius; Caglayan, Evren; Kramer, Tilmann; Baldus, Stephan; Schermuly, Ralph T; Tallquist, Michelle D; Rosenkranz, Stephan

    2015-05-01

    Despite modern therapies, pulmonary arterial hypertension (PAH) harbors a high mortality. Vascular remodeling is a hallmark of the disease. Recent clinical studies revealed that antiremodeling approaches with tyrosine-kinase inhibitors such as imatinib are effective, but its applicability is limited by significant side effects. Although imatinib has multiple targets, expression analyses support a role for platelet-derived growth factor (PDGF) in the pathobiology of the disease. However, its precise role and downstream signaling events have not been established. Patients with PAH exhibit enhanced expression and phosphorylation of β PDGF receptor (βPDGFR) in remodeled pulmonary arterioles, particularly at the binding sites for phophatidyl-inositol-3-kinase and PLCγ at tyrosine residues 751 and 1021, respectively. These signaling molecules were identified as critical downstream mediators of βPDGFR-mediated proliferation and migration of pulmonary arterial smooth muscle cells. We, therefore, investigated mice expressing a mutated βPDGFR that is unable to recruit phophatidyl-inositol-3-kinase and PLCγ (βPDGFR(F3/F3)). PDGF-dependent Erk1/2 and Akt phosphorylation, cyclin D1 induction, and proliferation, migration, and protection against apoptosis were abolished in βPDGFR(F3/F3) pulmonary arterial smooth muscle cells. On exposure to chronic hypoxia, vascular remodeling of pulmonary arteries was blunted in βPDGFR(F3/F3) mice compared with wild-type littermates. These alterations led to protection from hypoxia-induced PAH and right ventricular hypertrophy. By means of a genetic approach, our data provide definite evidence that the activated βPDGFR is a key contributor to pulmonary vascular remodeling and PAH. Selective disruption of PDGF-dependent phophatidyl-inositol-3-kinase and PLCγ activity is sufficient to abolish these pathogenic responses in vivo, identifying these signaling events as valuable targets for antiremodeling strategies in PAH. © 2015 American

  15. Tree size predicts vascular epiphytic richness of traditional cultivated tea plantations in Southwestern China

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    Qing Wang

    2017-04-01

    Full Text Available Species–area relationship has been widely addressed on many plant communities, but very few have conducted on epiphytic communities. Epiphytic plants are plentiful on ancient tea trees (Camelia sinensis var. assamica in the well-known Jingmai tea plantation area, Langcang region of Yunnan Province, SW China, and add to the plant community biodiversity. We investigated 343 tea trees with various ground diameter, canopy area, under branch height, and tree height. A total of 146 vascular epiphytic plants, belonging to 19 species in seven families were recorded from the trunk or branches of 93 (27.11% investigated trees. We examined in situ abundance, richness, and diversity (Shannon–Weiner index of the recorded vascular epiphytes, and their relationships to tree variables. Our results showed that the distribution (abundance, richness, and diversity of epiphytic plants are significantly related to the canopy area (p<0.05 and basal diameter (p<0.0001 of tea trees, supporting their use as key factors and good predictor for the epiphyte’s appearance in this type of agro-ecosystems. We also concluded that the species–area relationship is a useful epiphytic species community research tool.

  16. Evaluation of direct effects of enoximone on systemic and pulmonary vascular bed in animals with a Jarvik total artificial heart.

    Science.gov (United States)

    Deleuze, P H; Rande, J L; Okude, J; Wan, F; Brunet, S; Thoraval, F R; Cachera, J P; Loisance, D Y

    1992-03-01

    Enoximone, a phosphodiesterase inhibitor, has positive inotropic and vasodilating actions. To evaluate specific effects of this drug on the systemic and pulmonary vascular bed, we administered enoximone as a 10-minute intravenous bolus at two different doses of 2 and 3 mg/kg of body weight, at different days, to five Holstein calves with a Jarvik 7-70 ml total artificial heart (Symbion, Inc., Salt Lake City, Utah). The calves were monitored for aortic pressure, right atrial pressure, pulmonary arterial pressure, and left atrial pressure. For each experiment cardiac output was maintained constant, and systemic and pulmonary vascular resistances were calculated at 0, 15, 30, and 60 minutes and every hour for 8 hours after infusion. Statistical analysis used analysis of variance and the paired t test with Bonferroni's correction. Data showed the following: (1) a marked systemic vasodilating action of enoximone at peak effect at 30 minutes with a 20% decrease in systemic vascular resistance from baseline value under constant cardiac output, returning progressively to normal values throughout the 8 hours; (2) a comparable effect for the two separate doses tested; (3) no specific action on the pulmonary vascular bed with "nonunidirectional" changes in pulmonary vascular resistance. This model was validated by the infusion of prostaglandin I2 in the same animals, at different days, which significantly decreased pulmonary vascular resistance of 50% at peak effect, under constant cardiac output. In summary, enoximone showed a proper systemic vasodilating effect with no specific action on the pulmonary vascular bed in an animal model of the total artificial heart. Decrease in pulmonary vascular resistances obtained with enoximone in clinical practice seems more related to the inotropic properties of the drug. Enoximone should not be administered in pulmonary hypertension, as suggested before.

  17. [Treatment for pulmonary arterial hypertension under the new French hospital financing system. Recommendations of the Pulmonary Vascular Diseases Working Group of the French Society of Pulmonary Medicine].

    Science.gov (United States)

    Sitbon, O; Humbert, M; Simonneau, G

    2005-11-05

    Activity-based financing (that is, casemix-based hospital payments, known as T2A) is intended to harmonize and improve the fairness of remuneration of public and private hospitals. T2A will ultimately rely mainly on a flat rate per admission, set according to the diagnosis-related group (DRG). Although payment for drugs is usually included in the DRG price, some expensive drugs will be reimbursed on an additional cost basis after implementation of a "best practices" agreement. Four drugs used for treatment of pulmonary arterial hypertension are eligible for this additional reimbursement: 3 prostacyclin derivatives (intravenous epoprostenol, inhaled iloprost, and subcutaneous treprostinil), and oral bosentan, an endothelin receptor antagonist. The Pulmonary Vascular Diseases working group of the French Society of Pulmonary Medicine has developed guidelines for the best practices in use of these drugs.

  18. Segmental pulmonary vascular resistances during oleic acid lung injury in rabbits.

    Science.gov (United States)

    Maarek, J M; Grimbert, F

    1994-10-01

    We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the segmental distribution of vascular resistance. Vascular occlusion pressures were measured in control and OA-injured preparations over 90 min. Capillary filtration coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg-1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs. Total pulmonary vascular resistance changed little in both control and OA-injured lungs. OA injury resulted in a 15% increase of the double occlusion capillary pressure. In addition, the contribution of the microvascular to the total vascular resistance rose from 8% to 22%. The increase in microvascular resistance was significant 15 min after OA on the arteriolar side and became significant 30 min later on the venular side. Oleic acid injury does not change the total pulmonary vascular resistance but alters the distribution of segmental resistances in the isolated rabbit lung, thereby contributing to the accumulation of lung water in this model of low pressure permeability edema.

  19. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia

    NARCIS (Netherlands)

    S.B. Bender (Shawn ); V.J. de Beer (Vincent Jacob); D.L. Tharp (Darla); E.D. van Deel (Elza); D.K. Bowles; D.J.G.M. Duncker (Dirk); H. Laughlin (Harold); D. Merkus (Daphne)

    2014-01-01

    textabstractVascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailabilit

  20. Pulmonary arterial wall distensibility assessed by intravascular ultrasound in children with congenital heart disease : an indicator for pulmonary vascular disease?

    NARCIS (Netherlands)

    Berger, Rolf M F; Cromme-Dijkhuis, Adri H; Hop, Wim C J; Kruit, Marco N; Hess, John; Berger, Rudolphus

    2002-01-01

    BACKGROUND: Both pulmonary hypertension and pulmonary overflow are associated with functional and structural changes of the pulmonary arterial wall. Current techniques to evaluate the pulmonary vasculature neglect the pulsatile nature of pulmonary flow. STUDY OBJECTIVES: To determine whether the dyn

  1. Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network.

    Science.gov (United States)

    Seo, Hyejin; Kim, Jinsun; Park, Gi-Hee; Kim, Yuri; Cho, Sung-Won

    2016-09-01

    Intimate crosstalk occurs between the pulmonary epithelium and the vascular network during lung development. The transcription factor forkhead box f1 (Foxf1) is expressed in the lung mesenchyme and plays an indispensable role in pulmonary angiogenesis. Sonic hedgehog (Shh), a signalling molecule, is expressed in lung epithelium and is required to establish proper angiogenesis. It has been suggested that Foxf1, a downstream target of the Shh signalling pathway, mediates interaction between angiogenesis and the epithelium in lung. However, there has been no clear evidence showing the mechanism how Foxf1 is regulated by Shh signalling pathway during lung development. In this study, we investigated the lung-specific enhancers of Foxf1 and the Gli binding on the enhancers. At first, we found three evolutionarily conserved Foxf1 enhancers, two of which were long-range enhancers. Of the long-range enhancers, one demonstrated tissue-specific activity in the proximal and distal pulmonary blood vessels, while the other one demonstrated activity only in distal blood vessels. At analogous positions in human, these long-range enhancers were included in a regulatory region that was reportedly repeatedly deleted in alveolar capillary dysplasia with misalignment of pulmonary vein patients, which indicates the importance of these enhancers in pulmonary blood vessel formation. We also determined that Gli increased the activity of one of these long-range enhancers, which was specific to distal blood vessel, suggesting that Shh regulates Foxf1 transcription in pulmonary distal blood vessel formation.

  2. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  3. Nox4 Is Expressed In Pulmonary Artery Adventitia And Contributes To Hypertensive Vascular Remodeling

    Science.gov (United States)

    Barman, Scott A.; Chen, Feng; Su, Yunchao; Dimitropoulou, Christiana; Wang, Yusi; Catravas, John D.; Han, Weihong; Orfi, Laszlo; Szantai-Kis, Csaba; Keri, Gyorgy; Szabadkai, Istvan; Barabutis, Nektarios; Rafikova, Olga; Rafikov, Ruslan; Black, Stephen M.; Jonigk, Danny; Giannis, Athanassios; Asmis, Reto; Stepp, David W.; Ramesh, Ganesan; Fulton, David J.R.

    2014-01-01

    OBJECTIVE Pulmonary Hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PA and determine the functional relevance of Nox4 in PH. APPROACH AND RESULTS Elevated expression of Nox4 was detected in hypertensive PA from 3 rat PH models and human PH using qRT-PCR, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of ROS production. Small molecule inhibitors of Nox4 reduced adventitial ROS generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and non-invasive indices of PA stiffness in monocrotaline (MCT)-treated rats as determined by morphometric analysis and high resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PA. In fibroblasts, Nox4 over-expression stimulated migration and proliferation and was necessary for matrix gene expression. CONCLUSIONS These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling and the development of PH. PMID:24947524

  4. Influence of vascular enhancement, age and gender on pulmonary perfused blood volume quantified by dual-energy-CTPA

    Energy Technology Data Exchange (ETDEWEB)

    Meinel, Felix G., E-mail: felix.meinel@med.uni-muenchen.de; Graef, Anita, E-mail: anita.graef@med.uni-muenchen.de; Sommer, Wieland H., E-mail: wieland.sommer@uni-muenchen.de; Thierfelder, Kolja M., E-mail: kolja.thierfelder@uni-muenchen.de; Reiser, Maximilian F., E-mail: maximilian.reiser@med.uni-muenchen.de; Johnson, Thorsten R.C., E-mail: thorsten.johnson@med.uni-muenchen.de

    2013-09-15

    Objectives: To determine the influence of technical and demographic parameters on quantification of pulmonary perfused blood volume (PBV) in dual energy computed tomography pulmonary angiography (DE-CTPA). Materials and methods: Pulmonary PBV was quantified in 142 patients who underwent DE-CTPA for suspected pulmonary embolism but in whom no thoracic pathologies were detected. Multivariate linear regression analysis was performed to calculate the influence of age, gender, enhancement of pulmonary trunk and enhancement difference between pulmonary trunk and left atrium (as a measure of timing) on PBV values. The resulting regression coefficients were used to calculate age-specific ranges of normal for PBV values adjusted for vascular enhancement and timing. Results: Enhancement of the pulmonary trunk (β = −0.29, p = 0.001) and enhancement difference between pulmonary trunk and left atrium (β = −0.24, p = 0.003) were found to significantly influence PBV values. Age (β = −0.33, p < 0.001) but not gender (β = 0.14, p = 0.05) had a significant negative influence on pulmonary PBV values. There was a 20% relative decrease of pulmonary PBV from patients aged <30 to patients over 80 years of age. Conclusions: DE-CTPA derived PBV values need to be corrected for age, vascular enhancement and timing but not for gender. The age-specific ranges of normal derived from this study can be used as a reference in future studies of PBV in pulmonary pathologies.

  5. Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS.

    Science.gov (United States)

    Rossetti, M; Guénard, H; Gabinski, C

    1996-11-01

    The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p resistance decreased by 28% (p resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.

  6. Non-invasive estimation of pulmonary vascular resistance in patients of pulmonary hypertension in congenital heart disease with unobstructed pulmonary flow

    Directory of Open Access Journals (Sweden)

    Arindam Pande

    2014-01-01

    Full Text Available Context: Pulmonary vascular resistance (PVR is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease accompanied by pulmonary arterial hypertension. Aim: The present study was planned to evaluate non-invasive echocardiographic parameters to assess pulmonary vascular resistance. Settings and Design: This prospective observational study included 44 patients admitted in the cardiology and pediatric cardiology ward of our institution for diagnostic or pre-operative catheter based evaluation of pulmonary arterial pressure and PVR. Materials and Methods: Detailed echocardiographic evaluation was carried out including tricuspid regurgitation velocity (TRV and velocity time integral of the right-ventricular outflow tract (VTI RVOT . These parameters were correlated with catheter-based measurements of PVR. Results: The TRV/VTI RVOT ratio correlated well with PVR measured at catheterization (PVRcath (r = 0.896, 95% confidence interval [CI] 0.816 to 0.9423, P < 0.001. Using the Bland-Altman analysis, PVR measurements derived from Doppler data showed satisfactory limits of agreement with catheterization estimated PVR. For a PVR of 6 Wood units (WU, a TRV/VTI RVOT value of 0.14 provided a sensitivity of 96.67% and a specificity of 92.86% (area under the curve 0.963, 95% confidence interval 0.858 to 0.997 and for PVR of 8 WU a TRV/VTI RVOT value of 0.17 provided a sensitivity of 79.17% and a specificity of 95% (area under the curve 0. 0.923, 95% confidence interval 0.801 to 0.982. Conclusions: Doppler-derived ratio of TRV/VTI RVOT is a simple, non-invasive index, which can be used to estimate PVR.

  7. Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

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    Hales Charles A

    2011-02-01

    Full Text Available Abstract Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP, ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.

  8. Herpes virus infection is associated with vascular remodeling and pulmonary hypertension in idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Fiorella Calabrese

    Full Text Available BACKGROUND: Pulmonary hypertension (PH represents an important complication of idiopathic pulmonary fibrosis (IPF with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68 induced pulmonary fibrosis was also assessed. METHODS: Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. RESULTS: A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003 and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01, poorer performance in the six minute walking test (6MWT; p = 0.002 and higher frequency of primary graft (PGD dysfunction after lung transplant (p = 0.02. Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004 and higher TGF-β expression (p = 0.002 were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03, poorer performance in the 6MWT (p = 0.008 and PGD (p = 0.02 after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients

  9. Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Calabrese, Fiorella; Kipar, Anja; Lunardi, Francesca; Balestro, Elisabetta; Perissinotto, Egle; Rossi, Emanuela; Nannini, Nazarena; Marulli, Giuseppe; Stewart, James P.; Rea, Federico

    2013-01-01

    Background Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Methods Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. Results A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01), poorer performance in the six minute walking test (6MWT; p = 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03), poorer performance in the 6MWT (p = 0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Conclusion

  10. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    Science.gov (United States)

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  11. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

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    Angelini Daniel J

    2013-01-01

    Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.

  12. In vivo quantitative evaluation of vascular parameters for angiogenesis based on sparse principal component analysis and aggregated boosted trees

    Science.gov (United States)

    Zhao, Fengjun; Liu, Junting; Qu, Xiaochao; Xu, Xianhui; Chen, Xueli; Yang, Xiang; Cao, Feng; Liang, Jimin; Tian, Jie

    2014-12-01

    To solve the multicollinearity issue and unequal contribution of vascular parameters for the quantification of angiogenesis, we developed a quantification evaluation method of vascular parameters for angiogenesis based on in vivo micro-CT imaging of hindlimb ischemic model mice. Taking vascular volume as the ground truth parameter, nine vascular parameters were first assembled into sparse principal components (PCs) to reduce the multicolinearity issue. Aggregated boosted trees (ABTs) were then employed to analyze the importance of vascular parameters for the quantification of angiogenesis via the loadings of sparse PCs. The results demonstrated that vascular volume was mainly characterized by vascular area, vascular junction, connectivity density, segment number and vascular length, which indicated they were the key vascular parameters for the quantification of angiogenesis. The proposed quantitative evaluation method was compared with both the ABTs directly using the nine vascular parameters and Pearson correlation, which were consistent. In contrast to the ABTs directly using the vascular parameters, the proposed method can select all the key vascular parameters simultaneously, because all the key vascular parameters were assembled into the sparse PCs with the highest relative importance.

  13. Long-term outcome of patients with persistent vascular obstruction on computed tomography pulmonary angiography 6 months after acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Golpe, Rafael; Llano, Luis A. Perez de; Olalla, Castro-Anon [The Respiratory Service, Hospital Lucus Augusti, Lugo (Spain)], e-mail: Rafael.golpe.gomez@sergas.es; Vazquez-Caruncho, Manuel [The Radiology Service, Hospital Lucus Augusti, Lugo (Spain); Gonzalez-Juanatey, Carlos [The Cardiology Service, Hospital Lucus Augusti, Lugo (Spain); Farinas, Maria Carmen [Internal Medicine Dept., Hospital Univ. Marques de Valdecilla, Santander (Spain)

    2012-09-15

    Background: The incidence and clinical significance of pulmonary residual thrombosis 6 months after an acute pulmonary embolism (PE) are still not well-known. Purpose: To evaluate the association between residual vascular obstruction and the risk of venous thromboembolism (VTE) recurrence or death. Material and Methods: Computed tomography pulmonary angiography (CTPA) was repeated in 97 consecutive patients 6 months after an acute episode of hemodynamically stable pulmonary embolism. We assessed the long-term consequences of residual thrombosis on vital status and incidence of recurrent VTE. Results: Six patients were lost for follow-up. The remaining 91 patients were classified according to the presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary vascular obstruction. After a mean {+-}SD of 2.91 {+-}0.99 years, there were eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ in the incidence of death or VTE recurrence. Conclusion: Persistent pulmonary vascular obstruction on 6-month CTPA did not predict long-term adverse outcome events.

  14. Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang JIANG; Ai-Guo DAI; Qi-Fang LI; Rui-Cheng HU

    2006-01-01

    The muscularization of non-muscular pulmonary arterioles is animportant pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-β 1 (TGF-β 1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of α-smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-β1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

  15. Genome wide expression analysis suggests perturbation of vascular homeostasis during high altitude pulmonary edema.

    Directory of Open Access Journals (Sweden)

    Manish Sharma

    Full Text Available BACKGROUND: High altitude pulmonary edema (HAPE is a life-threatening form of non-cardiogenic edema which occurs in unacclimatized but otherwise normal individuals within two to four days after rapid ascent to altitude beyond 3000 m. The precise pathoetiology and inciting mechanisms regulating HAPE remain unclear. METHODOLOGY/PRINCIPLE FINDINGS: We performed global gene expression profiling in individuals with established HAPE compared to acclimatized individuals. Our data suggests concurrent modulation of multiple pathways which regulate vascular homeostasis and consequently lung fluid dynamics. These pathways included those which regulate vasoconstriction through smooth muscle contraction, cellular actin cytoskeleton rearrangements and endothelial permeability/dysfunction. Some notable genes within these pathways included MYLK; rho family members ARGEF11, ARHGAP24; cell adhesion molecules such as CLDN6, CLDN23, PXN and VCAM1 besides other signaling intermediates. Further, several important regulators of systemic/pulmonary hypertension including ADRA1D, ECE1, and EDNRA were upregulated in HAPE. We also observed significant upregulation of genes involved in paracrine signaling through chemokines and lymphocyte activation pathways during HAPE represented by transcripts of TNF, JAK2, MAP2K2, MAP2K7, MAPK10, PLCB1, ARAF, SOS1, PAK3 and RELA amongst others. Perturbation of such pathways can potentially skew vascular homeostatic equilibrium towards altered vascular permeability. Additionally, differential regulation of hypoxia-sensing, hypoxia-response and OXPHOS pathway genes in individuals with HAPE were also observed. CONCLUSIONS/SIGNIFICANCE: Our data reveals specific components of the complex molecular circuitry underlying HAPE. We show concurrent perturbation of multiple pathways regulating vascular homeostasis and suggest multi-genic nature of regulation of HAPE.

  16. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.

    Science.gov (United States)

    Haberzettl, Petra; O'Toole, Timothy E; Bhatnagar, Aruni; Conklin, Daniel J

    2016-12-01

    Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diets, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or to concentrated PM2.5 (CAP) for 9 or 30 days, and changes in systemic and organ-specific insulin sensitivity and inflammation were measured. In control diet-fed mice, exposure to CAP for 30 days decreased insulin-stimulated Akt phosphorylation in lung, heart, and aorta but not in skeletal muscle, adipose tissue, and liver and did not affect adiposity or systemic glucose tolerance. In HFD-fed mice, 30-day CAP exposure suppressed insulin-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation in skeletal muscle and increased adipose tissue inflammation and systemic glucose intolerance. In control diet-fed mice, a 9-day CAP exposure was sufficient to suppress insulin-stimulated Akt and eNOS phosphorylation and to decrease IκBα (inhibitor of the transcription factor NF-κB levels in the aorta. Treatment with the antioxidant TEMPOL or lung-specific overexpression of ecSOD prevented CAP-induced vascular insulin resistance and inflammation. Short-term exposure to PM2.5 induces vascular insulin resistance and inflammation triggered by a mechanism involving pulmonary oxidative stress. Suppression of vascular insulin signaling by PM2.5 may accelerate the progression to systemic insulin resistance, particularly in the context of diet-induced obesity. Citation: Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. 2016. Exposure to fine

  17. [Clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño].

    Science.gov (United States)

    Ormeño Julca, Alexis Jose; Alvarez Murillo, Carlos Melchor; Amoretti Alvino, Pedro Miguel; Florian Florian, Angel Aladino; Castro Johanson, Rosa Aurora; Celi Perez, Maria Danisa; Huamán Prado, Olga Rocío

    2017-01-01

    The hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN) are distinct pulmonary vascular complications of portal hypertension (PHT) and are associated with increased morbidity and mortality. To describe the clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño. We included patients with HTP hospitalized from January 2012 to June 2013 and that during its evolution progressed with SHP or HTPP. For analysis, they were divided into a first group of patients with liver cirrhosis and a second group with extrahepatic portal vein obstruction. Of 22 patients with HPT 45.5% were male and the age range was between 1 month and 17 years. The etiology in the group of cirrhosis (n=14) was: autoimmune hepatitis (35.7%), cryptogenic cirrhosis (35.7%), inborn error of metabolism (14.3%), chronic viral hepatitis C (7.15%) virus and atresia extra-hepatic bile ducts (7.15%). Pulmonary vascular complications more frequently occurred in patients with liver cirrhosis (1 case of HPS and a case of PPHTN). They most often dyspnea, asthenia, edema, malnutrition, ascites, hypersplenism and gastrointestinal bleeding from esophageal varices was found. Also, they had elevated ALT values, alkaline phosphatase and serum albumin values decreased. In children with pulmonary hypertension, pulmonary vascular complications are rare. In the evaluation of these patients pulse oximetry should be included to detect hypoxemia and ubsequently a Doppler echocardiography and contrast echocardiography necessary. Dueto the finding of systolic pulmonary hypertension it is necessary to perform right heart catheterization.

  18. Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Kochetkova, Evgenia A; Ugai, Ludmila G; Maistrovskaia, Yuliya V; Nevzorova, Vera A

    2017-04-01

    Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

  19. Looking inside the heart: a see-through view of the vascular tree

    Science.gov (United States)

    Nehrhoff, Imke; Ripoll, Jorge; Samaniego, Rafael; Desco, Manuel; Gómez-Gaviro, Maria Victoria

    2017-01-01

    The ability to acquire 3D images of the heart and its vasculature at cellular resolution facilitates a more detailed study of many heart diseases. Here, we describe a novel technique to image in 3D the heart vasculature by combining the CUBIC clearing protocol combined with in vivo administration of fluorescent-labeled lectin. The use of these techniques in combination with Selective Plane Illumination Microscopy (SPIM) made it possible to obtain high resolution 3D images of the cardiac vascular tree. This methodological approach may enhance the visualization of 3D images of the cardiac vasculature remodeling associated with coronary disease. PMID:28663930

  20. Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.

    1981-01-01

    In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a /sup 24/Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

  1. Vascular cell transcriptomic changes to exercise training differ directionally along and between skeletal muscle arteriolar trees.

    Science.gov (United States)

    Laughlin, M Harold; Yang, Hsiao T; Tharp, Darla L; Rector, R Scott; Padilla, Jaume; Bowles, Douglas K

    2017-02-01

    EXT-induced arteriolar adaptations in skeletal muscle are heterogeneous because of spatial variations in muscle fiber type composition and fiber recruitment patterns during exercise. The purpose of this report is to summarize a series of experiments conducted to test the hypothesis that changes in vascular gene expression are signaled by alterations in shear stress resulting from increases in blood flow, muscle fiber type composition, and fiber recruitment patterns. We also report results from a follow-up study of Ankrd23, one gene whose expression was changed by EXT. We expected to see differences in magnitude of changes in gene expression along arteriolar trees and between/among arteriolar trees but similar directional changes. However, transcriptional profiles of arterioles/arteries from OLETF rats exposed to END or SIT reveal that EXT does not lead to similar directional changes in the transcriptome among arteriolar trees of different skeletal muscles or along arteriolar trees within a particular muscle. END caused the most changes in gene expression in 2A arterioles of soleus and white gastrocnemius with little to no changes in the FAs. Ingenuity Pathway Analysis across vessels revealed significant changes in gene expression in 18 pathways. EXT increased expression of some genes (Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein-binding protein, alpha (Gnat1), and Bcl2l1) in all arterioles examined, but decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). Many contractile and/or structural protein genes were increased by SIT in the gastrocnemius FA, but the same genes exhibited decreased expression in red gastrocnemius arterioles. Ankrd23 mRNA levels increased with increasing branch order in the gastrocnemius arteriolar tree and were increased 19-fold in gastrocnemius muscle FA by SIT. Follow-up experiments indicate that Ankrd23 mRNA level was increased 14-fold in cannulated gastrocnemius FA when

  2. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

    Science.gov (United States)

    Badejo, Adeleke M; Hodnette, Chris; Dhaliwal, Jasdeep S; Casey, David B; Pankey, Edward; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2010-09-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

  3. Fractal Dimension Analysis of MDCT Images for Quantifying the Morphological Changes of the Pulmonary Artery Tree in Patients with Pulmonary Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haitao; Li, Ning; Guo, Lijun; Gao, Fei; Liu, Cheng [Shandong University, Shandong Medical Imaging Research Institute, Shandong (Korea, Republic of)

    2011-06-15

    The aim of this study was to use fractal dimension (FD) analysis on multidetector CT (MDCT) images for quantifying the morphological changes of the pulmonary artery tree in patients with pulmonary hypertension (PH). Fourteen patients with PH and 17 patients without PH as controls were studied. All of the patients underwent contrast-enhanced helical CT and transthoracic echocardiography. The pulmonary artery trees were generated using post-processing software, and the FD and projected image area of the pulmonary artery trees were determined with Image J software in a personal computer. The FD, the projected image area and the pulmonary artery pressure (PAP) were statistically evaluated in the two groups. The FD, the projected image area and the PAP of the patients with PH were higher than those values of the patients without PH (p < 0.05, t-test). There was a high correlation of FD with the PAP (r = 0.82, p < 0.05, partial correlation analysis). There was a moderate correlation of FD with the projected image area (r = 0.49, p < 0.05, partial correlation analysis). There was a correlation of the PAP with the projected image area (r = 0.65, p < 0.05, Pearson correlation analysis). The FD of the pulmonary arteries in the PH patients was significantly higher than that of the controls. There is a high correlation of FD with the PAP.

  4. Prevention of pulmonary vascular and myocardial remodeling by the combined tyrosine and serine-/threonine kinase inhibitor, sorafenib, in pulmonary hypertension and right heart failure

    Directory of Open Access Journals (Sweden)

    M. Klein

    2008-06-01

    Full Text Available Inhibition of tyrosine kinases can reverse pulmonary hypertension but little is known about the role of serine-/threonine kinases in vascular and myocardial remodeling. We investigated the effects of sorafenib, an inhibitor of the tyrosine kinases VEGFR, PDGFR and c-kit as well as the serine-/threonine kinase Raf-1, in pulmonary hypertension and right ventricular (RV pressure overload. In monocrotaline treated rats, sorafenib (10 mg·kg–1·d–1 p.o. reduced pulmonary arterial pressure, pulmonary artery muscularization and RV hypertrophy, and improved systemic hemodynamics (table 1. Sorafenib prevented phosphorylation of Raf-1 and suppressed activation of downstream signaling pathways (Erk 1/2. After pulmonary banding, sorafenib, but not the PDGFR/c-KIT/ABL-inhibitor imatinib reduced RV mass and RV filling pressure significantly. Congruent with these results, sorafenib only prevented ERK phosphorylation and vasopressin induced hypertrophy of the cardiomyocyte cell line H9c2 dose dependently (IC50 = 300 nM. Combined inhibition of tyrosine and serine-/threonine kinases by sorafenib prevents vascular and cardiac remodeling in pulmonary hypertension, which is partly mediated via inhibition of the Raf kinase pathway.

  5. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  6. Classification decision tree algorithm assisting in diagnosing solitary pulmonary nodule by SPECT/CT fusion imaging

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To develop a classification tree algorithm to improve diagnostic performances of 99mTc-MIBI SPECT/CT fusion imaging in differentiating solitary pulmonary nodules(SPNs).Methods Forty-four SPNs,including 30 malignant cases and 14 benign ones that were eventually pathologically identified,were included in this prospective study.All patients received 99Tcm-MIBI SPECT/CT scanning at an early stage and a delayed stage before operation.Thirty predictor variables,including 11 clinical variables,4 variable...

  7. Socio Demographic Profile and Clinical Presentation of Collagen Vascular Disease with Pulmonary Symptoms: A Descriptive Cross Sectional Study

    Directory of Open Access Journals (Sweden)

    Parul Vadgama

    2013-02-01

    Full Text Available Introduction: Collagen Vascular Disease presented with varied systemic symptoms including pulmonary symptoms, commonly breathless on exertion; dry cough; cough with expectoration; chest pain; and hemoptysis. The current study was conducted to know socio demographic profile and clinical presentation of patient coming with Collagen Vascular Disease having pulmonary symptoms. Methodology: This was a descriptive cross sectional study conducted among Collagen Vascular Disease patient coming with pulmonary symptoms in outpatient department. Results: Among the 50 patients 40% patients were having SC followed by SLE (30%. Most common age group was 31 to 40 year of age followed by 21 to 30 year of age. Both these group contribute more than half of the cases. Eighty percent patients were female with female to male ratio was 4:1. The most common chest symptom in the patients was breathlessness (50% and fatigue (50%, followed by cough (46% and chest pain (18%. The most common sign was Crackles (32% followed by clubbing in 22% of patients. Conclusion: Female and young - middle age more commonly presented with Collagen Vascular Disease. Most of the patients when presented were having wide-ranging pulmonary symptoms-signs indicating extensive involvement of lung tissues which emphasis need for early diagnosis and treatment. [Natl J of Med Res 2013; 3(1.000: 27-29

  8. Integration of complex data sources to provide biologic insight into pulmonary vascular disease (2015 Grover Conference Series)

    Science.gov (United States)

    Chan, Stephen Y.

    2016-01-01

    Abstract The application of complex data sources to pulmonary vascular diseases is an emerging and promising area of investigation. The use of -omics platforms, in silico modeling of gene networks, and linkage of large human cohorts with DNA biobanks are beginning to bear biologic insight into pulmonary hypertension. These approaches to high-throughput molecular phenotyping offer the possibility of discovering new therapeutic targets and identifying variability in response to therapy that can be leveraged to improve clinical care. Optimizing the methods for analyzing complex data sources and accruing large, well-phenotyped human cohorts linked to biologic data remain significant challenges. Here, we discuss two specific types of complex data sources—gene regulatory networks and DNA-linked electronic medical record cohorts—that illustrate the promise, challenges, and current limitations of these approaches to understanding and managing pulmonary vascular disease. PMID:27683602

  9. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  10. Clinical studies on the distribution of the pulmonary blood flow at rest and with exercise in mitral stenosis in connection with the reversibility of the pulmonary vascular lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Tomio

    1988-09-01

    In order to determine the severity and reversibilty of pathologic changes in the pulmonary vascular bed in mitral stenosis (MS), a retrospective review was made of pulmonary perfusion scans obtained at rest and during exercise in a series of 60 subjects - 37 patients with MS, 8 with mitral regurgitation (MR), 7 with aortic regurgitation and stenosis (ARS), and 8 normal persons (N). As expressed by Q(U/L), an increased ratio of pulmonary blood flow in the upper part to that in the lower part of the lung was significantly associated with exercise in the MR and ARS groups, as well as the N group. In the MS group, Q(U/L) patterns associated with exercise fell into three categories: (I) an increase in Q(U/L) that was lower at rest than 1.1, (II) an increase in Q(U/L) that was higher at rest that 1.1, and (III) a decrease in Q(U/L). The MS group I had the worst preoperative parameters for cardiac and pulmonary function, followed by the group II and then the group III. For 23 patients receiving mitral valve replacement, postoperative parameters, including mean pulmonary arterial pressure, cardiac index, and pulmonary arterial resistance, were worse in the group II than the groups I and III. The results suggest that organic changes in the pulmonary vascular bed, as opposed to its reversible changes in the groups I and III, have occurred in the group II. Q(U/L) changes associated with exercise may be of value in determining the severity of MS. (Namekawa, K.).

  11. Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

    Energy Technology Data Exchange (ETDEWEB)

    Fabregat-Andrés, Óscar, E-mail: osfabregat@gmail.com [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Estornell-Erill, Jordi [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Ridocci-Soriano, Francisco [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Pérez-Boscá, José Leandro [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); García-González, Pilar [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Payá-Serrano, Rafael [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Morell, Salvador [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Cortijo, Julio [Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Farmacologia. Universitat de Valencia, Valencia (Spain)

    2016-03-15

    Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

  12. Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    Science.gov (United States)

    Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

    2016-05-01

    Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided.

  13. Regulation of Pulmonary Vascular Tone in Health and Disease: Special emphasis on exercise and pulmonary hypertension after myocardial infarction

    NARCIS (Netherlands)

    B. Houweling (Birgit)

    2007-01-01

    textabstractHigh bloodpressure in the pulmonary circulation is called pulmonary hypertension (PH). In patients with PH, the balance between vasodilators and vasoconstrictors is disturbed. PH is an important cause of death; it is characterized by elevated levels of pulmonary artery pressure a

  14. Classification decision tree algorithm assisting in diagnosing solitary pulmonary nodule by SPECT/CT fusion imaging

    Institute of Scientific and Technical Information of China (English)

    Qiang Yongqian; Guo Youmin; Jin Chenwang; Liu Min; Yang Aimin; Wang Qiuping; Niu Gang

    2008-01-01

    Objective To develop a classification tree algorithm to improve diagnostic performances of 99mTc-MIBI SPECT/CT fusion imaging in differentiating solitary pulmonary nodules (SPNs). Methods Forty-four SPNs, including 30 malignant cases and 14 benign ones that were eventually pathologically identified, were included in this prospective study. All patients received 99Tcm-MIBI SPECT/CT scanning at an early stage and a delayed stage before operation. Thirty predictor variables, including 11 clinical variables, 4 variables of emission and 15 variables of transmission information from SPECT/CT scanning, were analyzed independently by the classification tree algorithm and radiological residents. Diagnostic rules were demonstrated in tree-topology, and diagnostic performances were compared with Area under Curve (AUC) of Receiver Operating Characteristic Curve (ROC). Results A classification decision tree with lowest relative cost of 0.340 was developed for 99Tcm-MIBI SPECT/CT scanning in which the value of Target/Normal region of 99Tcm-MIBI uptake in the delayed stage and in the early stage, age, cough and specula sign were five most important contributors. The sensitivity and specificity were 93.33% and 78. 57e, respectively, a little higher than those of the expert. The sensitivity and specificity by residents of Grade one were 76.67% and 28.57%, respectively, and AUC of CART and expert was 0.886±0.055 and 0.829±0.062, respectively, and the corresponding AUC of residents was 0.566±0.092. Comparisons of AUCs suggest that performance of CART was similar to that of expert (P=0.204), but greater than that of residents (P<0.001). Conclusion Our data mining technique using classification decision tree has a much higher accuracy than residents. It suggests that the application of this algorithm will significantly improve the diagnostic performance of residents.

  15. Pulmonary vascular response during phases of canine heartworm disease: scanning electron microscopic study.

    Science.gov (United States)

    Schaub, R G; Rawlings, C A

    1980-07-01

    Pulmonary arteries and veins of 14 dogs in phases of heartworm disease (Dirofilaria immitis infection) were examined by scanning electron microscopy. Two dogs were infected with D immitis microfilaria only, whereas 12 dogs were infected with adult D immitis. Seven of the dogs infected with adult worms were untreated. Two of these 7 dogs had natural infections of unknown duration introduced by mosquito bite, whereas 5 were experimentally infected for 30 days. The remaining five dogs were experimentally infected for 1 year and had worms removed by drug therapy. These five dogs were maintained 12 months after treatment. Arteries and veins from dogs infected with microfilaria had a continuous sheet of endothelial cells. Arterial endothelium from the seven nontreated dogs infected with adult heartworms exhibited swirling patterns, pore formation, and separation of intercellular junctions. Arteries from all dogs had numerous endothelialized villus protrusions; veins had similar, less extensive changes. Arteries and veins from experimentally infected dogs were similar to naturally infected dogs, indicating the infection procedure produced lesions similar to that normally seen in heartworm disease. The extent of vascular lesions was reduced in four of the five treated dogs that had been infected with adult worms. Adult worms, not microfilaria, may produce the vascular lesions seen in heartworm disease. Lesions will regress if worms are removed from the circulation. Lesions may be caused by generation of humoral factors initiated by the presence of adult worms.

  16. Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension (2015 Grover Conference series).

    Science.gov (United States)

    Pullamsetti, Soni S; Perros, Frédéric; Chelladurai, Prakash; Yuan, Jason; Stenmark, Kurt

    2016-12-01

    Pulmonary hypertension (PH) is a complex and multifactorial disease involving genetic, epigenetic, and environmental factors. Numerous stimuli and pathological conditions facilitate severe vascular remodeling in PH by activation of a complex cascade of signaling pathways involving vascular cell proliferation, differentiation, and inflammation. Multiple signaling cascades modulate the activity of certain sequence-specific DNA-binding transcription factors (TFs) and coregulators that are critical for the transcriptional regulation of gene expression that facilitates PH-associated vascular cell phenotypes, as demonstrated by several studies summarized in this review. Past studies have largely focused on the role of the genetic component in the development of PH, while the presence of epigenetic alterations such as microRNAs, DNA methylation, histone levels, and histone deacetylases in PH is now also receiving increasing attention. Epigenetic regulation of chromatin structure is also recognized to influence gene expression in development or disease states. Therefore, a complete understanding of the mechanisms involved in altered gene expression in diseased cells is vital for the design of novel therapeutic strategies. Recent technological advances in DNA sequencing will provide a comprehensive improvement in our understanding of mechanisms involved in the development of PH. This review summarizes current concepts in TF and epigenetic control of cell phenotype in pulmonary vascular disease and discusses the current issues and possibilities in employing potential epigenetic or TF-based therapies for achieving complete reversal of PH.

  17. Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension.

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    Stenmark, Kurt R; Tuder, Rubin M; El Kasmi, Karim C

    2015-11-15

    Pulmonary hypertension (PH) is a complex, multifactorial syndrome that remains poorly understood despite decades of research. PH is characterized by profound pulmonary artery (PA) remodeling that includes significant fibro-proliferative and inflammatory changes of the PA adventitia. In line with the emerging concept that PH shares key features with cancer, recent work centers on the idea that PH results from a multistep process driven by reprogramming of gene-expression patterns that govern changes in cell metabolism, inflammation, and proliferation. Data demonstrate that in addition to PA endothelial cells and smooth muscle cells, adventitial fibroblasts from animals with experimental hypoxic PH and from humans with PH (hereafter, termed PH-Fibs) exhibit proinflammatory activation, increased proliferation, and apoptosis resistance, all in the context of metabolic reprogramming to aerobic glycolysis. PH-Fibs can also recruit, retain, and activate naïve macrophages (Mϕ) toward a proinflammatory/proremodeling phenotype through secretion of chemokines, cytokines, and glycolytic metabolites, among which IL-6 and lactate play key roles. Furthermore, these fibroblast-activated Mϕ (hereafter, termed FAMϕ) exhibit aerobic glycolysis together with high expression of arginase 1, Vegfa, and I1lb, all of which require hypoxia-inducible factor 1α and STAT3 signaling. Strikingly, in situ, the adventitial Mϕ phenotype in the remodeled PA closely resembles the Mϕ phenotype induced by fibroblasts in vitro (FAMϕ), suggesting that FAMϕ crosstalk involving metabolic and inflammatory signals is a critical, pathogenetic component of vascular remodeling. This review discusses metabolic and inflammatory changes in fibroblasts and Mϕ in PH with the goal of raising ideas about new interventions to abrogate remodeling in hypoxic forms of PH.

  18. The mast cell - B-cell axis in lung vascular remodeling and pulmonary hypertension.

    Science.gov (United States)

    Breitling, Siegfried; Hui, Zhang; Zabini, Diana; Hu, Yijie; Hoffmann, Julia; Goldenberg, Neil M; Tabuchi, Arata; Buelow, Roland; Dos Santos, Claudia; Kuebler, Wolfgang Michael

    2017-02-24

    Over the past years, a critical role for the immune system and in particular, for mast cells, in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B-cells and autoimmunity. Experiments were performed in Sprague Dawley rats and B-cell deficient JH-KO rats in the monocrotaline, sugen-hypoxia and the aortic banding model of PH. Hemodynamics, cell infiltration, IL-6 expression, and vascular remodeling were analyzed. Gene array analyses revealed constituents of immunoglobulins as most prominently regulated mast cell dependent genes in the lung in experimental PH. IL-6 was shown to link mast cells to B-cells, as a) IL-6 was upregulated and colocalized with mast cells and was reduced by mast cell stabilizers, and b) IL-6 or mast cell blockade reduced B-cells in lungs of monocrotaline-treated rats. A functional role for B-cells in PH was demonstrated, in that either blocking B-cells by an anti-CD20 antibody or B-cell deficiency in JH-KO rats attenuated right ventricular systolic pressure and vascular remodeling in experimental PH. We here identify a mast cell - B-cell axis driven by IL-6 as critical immune pathway in the pathophysiology of PH. Our results provide novel insights into the role of the immune system in PH, which may be therapeutically exploited by targeted immunotherapy.

  19. Predicting smear negative pulmonary tuberculosis with classification trees and logistic regression: a cross-sectional study

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    Kritski Afrânio

    2006-02-01

    Full Text Available Abstract Background Smear negative pulmonary tuberculosis (SNPT accounts for 30% of pulmonary tuberculosis cases reported yearly in Brazil. This study aimed to develop a prediction model for SNPT for outpatients in areas with scarce resources. Methods The study enrolled 551 patients with clinical-radiological suspicion of SNPT, in Rio de Janeiro, Brazil. The original data was divided into two equivalent samples for generation and validation of the prediction models. Symptoms, physical signs and chest X-rays were used for constructing logistic regression and classification and regression tree models. From the logistic regression, we generated a clinical and radiological prediction score. The area under the receiver operator characteristic curve, sensitivity, and specificity were used to evaluate the model's performance in both generation and validation samples. Results It was possible to generate predictive models for SNPT with sensitivity ranging from 64% to 71% and specificity ranging from 58% to 76%. Conclusion The results suggest that those models might be useful as screening tools for estimating the risk of SNPT, optimizing the utilization of more expensive tests, and avoiding costs of unnecessary anti-tuberculosis treatment. Those models might be cost-effective tools in a health care network with hierarchical distribution of scarce resources.

  20. Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension.

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    Makoto Sahara

    Full Text Available BACKGROUND: An antianginal K(ATP channel opener nicorandil has various beneficial effects on cardiovascular systems; however, its effects on pulmonary vasculature under pulmonary arterial hypertension (PAH have not yet been elucidated. Therefore, we attempted to determine whether nicorandil can attenuate monocrotaline (MCT-induced PAH in rats. MATERIALS AND METHODS: Sprague-Dawley rats injected intraperitoneally with 60 mg/kg MCT were randomized to receive either vehicle; nicorandil (5.0 mg·kg(-1·day(-1 alone; or nicorandil as well as either a K(ATP channel blocker glibenclamide or a nitric oxide synthase (NOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME, from immediately or 21 days after MCT injection. Four or five weeks later, right ventricular systolic pressure (RVSP was measured, and lung tissue was harvested. Also, we evaluated the nicorandil-induced anti-apoptotic effects and activation status of several molecules in cell survival signaling pathway in vitro using human umbilical vein endothelial cells (HUVECs. RESULTS: Four weeks after MCT injection, RVSP was significantly increased in the vehicle-treated group (51.0±4.7 mm Hg, whereas it was attenuated by nicorandil treatment (33.2±3.9 mm Hg; P<0.01. Nicorandil protected pulmonary endothelium from the MCT-induced thromboemboli formation and induction of apoptosis, accompanied with both upregulation of endothelial NOS (eNOS expression and downregulation of cleaved caspase-3 expression. Late treatment with nicorandil for the established PAH was also effective in suppressing the additional progression of PAH. These beneficial effects of nicorandil were blocked similarly by glibenclamide and l-NAME. Next, HUVECs were incubated in serum-free medium and then exhibited apoptotic morphology, while these changes were significantly attenuated by nicorandil administration. Nicorandil activated the phosphatidylinositol 3-kinase (PI3K/Akt and extracellular signal-regulated kinase (ERK

  1. A feasible method for non-invasive measurement of pulmonary vascular resistance in pulmonary arterial hypertension: Combined use of transthoracic Doppler-echocardiography and cardiac magnetic resonance. Non-invasive estimation of pulmonary vascular resistance.

    Science.gov (United States)

    Yan, Chaowu; Xu, Zhongying; Jin, Jinglin; Lv, Jianhua; Liu, Qiong; Zhu, Zhenhui; Pang, Kunjing; Shi, Yisheng; Fang, Wei; Wang, Yang

    2015-12-07

    Transthoracic Doppler-echocardiography (TTE) can estimate mean pulmonary arterial pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) reliably, and cardiac magnetic resonance (CMR) is the best modality for non-invasive measurement of cardiac output (CO). We speculated that the combined use of TTE and CMR could provide a feasible method for non-invasive measurement of pulmonary vascular resistance (PVR) in pulmonary arterial hypertension (PAH). Right heart catheterization (RHC) was undertaken in 77 patients (17M/60F) with PAH, and simultaneous TTE was carried out to evaluate MPAP, PCWP and CO. Within 2 days, CO was measured again with CMR in similar physiological status. Then, PVR was calculated with the integrated non-invasive method: TTE-derived (MPAP-PCWP)/CMR-derived CO and the isolated TTE method: TTE-derived (MPAP-PCWP)/TTE-derived CO, respectively. The PVR calculated with integrated non-invasive method correlated well with RHC-calculated PVR (r = 0.931, 95% confidence interval 0.893 to 0.956). Between the integrated non-invasive PVR and RHC-calculated PVR, the Bland-Altman analysis showed the satisfactory limits of agreement (mean value: - 0.89 ± 2.59). In comparison, the limits of agreement were less satisfactory between TTE-calculated PVR and RHC-calculated PVR (mean value: - 1.80 ± 3.33). Furthermore, there were excellent intra- and inter-observer correlations for the measurements of TTE and CMR (P measurement of PVR is very important in clinical practice. Up to now, however, the widely accepted non-invasive method is still unavailable. Since TTE can estimate (MPAP-PCWP) reliably and CMR is the best image modality for the measurement of CO, the combined use of two modalities has the potential to determine PVR non-invasively. In this research, the integrated non-invasive method showed good diagnostic accuracy and repeatability compared with RHC. Therefore, it might be a feasible method for non-invasive measurement of PVR in patients

  2. Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    李启芳; 戴爱国

    2004-01-01

    Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4±0.4) mmHg, P<0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P<0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0.20±0.02, P<0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P<0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0.01). Conclusion HIF-1α and VEGF are both involved in the

  3. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia.

    Science.gov (United States)

    Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; van Deel, Elza D; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold; Merkus, Daphne

    2014-04-15

    Vascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailability. Since NO normally limits endothelin (ET) action, we examined the hypothesis that reduced systemic vasodilatation during exercise in FH swine results from increased ET-mediated vasoconstriction. Systemic and pulmonary vascular responses to exercise were examined in chronically instrumented normal and FH swine in the absence and presence of the ETA/B receptor antagonist tezosentan. Intrinsic reactivity to ET was further assessed in skeletal muscle arterioles. FH swine exhibited ∼9-fold elevation in total plasma cholesterol versus normal swine. Similar to our recent findings, systemic, not pulmonary, vasodilatation during exercise was reduced in FH swine. Blockade of ET receptors caused marked systemic vasodilatation at rest and during exercise in normal swine that was significantly reduced in FH swine. The reduced role of ET in FH swine in vivo was not the result of decreased arteriolar ET responsiveness, as responsiveness was increased in isolated arterioles. Smooth muscle ET receptor protein content was unaltered by FH. However, circulating plasma ET levels were reduced in FH swine. ET receptor antagonism caused pulmonary vasodilatation at rest and during exercise in normal, but not FH, swine. Therefore, contrary to our hypothesis, FH swine exhibit a generalised reduction in the role of ET in regulating vascular tone in vivo probably resulting from reduced ET production. This may represent a unique vascular consequence of severe familial hypercholesterolaemia.

  4. CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARTERIAL HYPERTENSION: VASCULAR WALL AS THE TARGET ORGAN IN COMORBID PATIENTS

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    N. A. Karoli

    2017-01-01

    Full Text Available Studies of endothelial dysfunction in patients with respiratory diseases have become relevant in recent years. Perhaps endothelial dysfunction and high arterial stiffness bind bronchopulmonary and cardiovascular diseases.Aim. To reveal features of disturbances of arterial wall vasoregulatory function in patients with chronic obstructive pulmonary disease (COPD in the presence and absence of arterial hypertension (HT.Material and methods. The study included 50 patients with COPD with normal blood pressure (BP and 85 patients with COPD and HT. Control group was presented by 20 practically healthy men comparable in age with COPD patients. Tests with reactive hyperemia (endothelium-dependent dilation and nitroglycerin (endothelium-independent dilation were performed in order to evaluate endothelium function. The number of desquamated endotheliocytes in the blood was determined.Results. In patients with COPD and HT in comparison with COPD patients without HT and healthy individuals more pronounced damages of the vascular wall, endothelium vasoregulatory function disturbances and a tendency to the reduction in endothelium-dependent vasodilation were determined both during COPD exacerbation and remission. These differences were most pronounced during the COPD exacerbation. In patients with COPD and HT in comparison with COPD patients without HT the damage of the vascular wall was more pronounced during the remission and endothelium-dependent dilatation disorder – during the exacerbation. The revealed disorders in patients with COPD and HT were associated with smoking status (r=0.61, p<0.01, severity of bronchial obstruction (r=-0.49, p<0.05, and hypoxemia (r=-0.76, p<0.01. We noted relationships between the parameters of 24-hour BP monitoring and remodeling of the brachial artery (r=0.34, p<0.05, endothelium lesion (r=0.25, p<0.05, and impairment of its vasoregulating function (r=-0.58, p<0.05. At that, the following parameters were important: the

  5. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

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    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  6. Hereditary hemorrhagic telangiectasia with bilateral pulmonary vascular malformations: A case report

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    Lončarević Olivera

    2016-01-01

    Full Text Available Introduction. Hereditary hemorrhagic telangiectasia (HHT also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signaling pathway of transforming growth factor β (TGF-β. The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and urinary tract. They can make a rupture with consequent serious bleeding that can end up with fatal outcome. Since there is a disruption of blood vessels of more than one organic system, the diagnosis is very complex and requires a multidisciplinary approach. Case report. We reported a 40-year-old female patient with a long-time evolution of problems, who was diagnosed and treated at the Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia, because of bilaterally pulmonary arteriovenous malformations associated with HHT. Embolization was performed in two acts, followed with normalization of clinical, radiological and functional findings with the cessation of hemoptysis, effort intolerance with a significant improvement of the quality of life. Conclusion. HHT is a rare dominant inherited multisystem disease that requires multidisciplinary approach to diagnosis and treatment. Embolization is the method of choice in the treatment of arteriovenous malformations with minor adverse effects and very satisfying therapeutic effect.

  7. Effect of C-myc Antisense Oligodeoxynucleotides on Hypoxia-induced Proliferation of Pulmonary Vascular Pericytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA,3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P<0.01), and elevate 3H-thymidine incorporation of PC (P<0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P<0.05), and 3H-thymidine incorporation of PC (P<0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

  8. Clearance of inhaled technetium-99m-DTPA as a clinical index of pulmonary vascular disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kon, O.M.; Daniil, Z.; Bois, R.M. du [Royal Brompton Hospital, Interstitial Lung Disease Unit, London (United Kingdom); Black, C.M. [Royal Free Hospital, Dept. of Rheumatology, London (United Kingdom)

    1999-01-01

    This study evaluated the utility of the clearance time of inhaled diethylenetriamine pentaacetate (DTPA) to distinguish pulmonary vascular disease from early fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) It was hypothesized that this would be preserved in patients with vascular disease compared with FA, despite similar gas-transfer deficits and matching lung volumes, because of the preservation of alveolar epithelial integrity. All patients had SSc and were categorized into a control group (C; n=9), pulmonary vascular group (VAS; n=14) or FA group (n=14) dependent on the appearance on a computed tomography (CT) scan and the transfer factor of the lung for carbon monoxide (TL,CO) (VAS and FA {<=}70%, C {>=}80%). All patients had a forced vital capacity (FVC) of >80%. The TL,CO (median) was similar in the VAS (57.5%) and FA (60%) groups. There was a significant difference in median DTPA clearance half-times between FA (21.25 min) and VAS (46.5 min) (p=0.014) and between FA and C (84.5 min) (p=0.0004). No difference was found between VAS and C (p=0.0778). Follow-up data from the VAS group showed no subsequent development of FA on the CT scan and no decrease in FVC (n=13, mean 42 months). These results suggest that clearance of diethylenetriamine pentaacetate is preserved in patients likely to have pulmonary vascular disease and may be useful in distinguishing fibrosing alveolitis from vascular disease in systemic sclerosis. (au) 22 refs.

  9. Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus.

    Science.gov (United States)

    Delaney, Cassidy; Gien, Jason; Grover, Theresa R; Roe, Gates; Abman, Steven H

    2011-12-01

    Maternal use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN), but little is known about 5-HT signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3-20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT-induced pulmonary vasoconstriction. In contrast, intrapulmonary infusions of GR127945 and SB206553, 5-HT 1B and 5-HT 2B receptor antagonists, respectively, had no effect on basal PVR or 5-HT-induced vasoconstriction. Pretreatment with fasudil, a Rho kinase inhibitor, blunted the effects of 5-HT infusion. Brief infusions of the SSRIs, sertraline and fluoxetine, caused potent and sustained elevations of PVR, which was sustained for over 60 min after the infusion. SSRI-induced pulmonary vasoconstriction was reversed by infusion of ketanserin and did not affect the acute vasodilator effects of acetylcholine. We conclude that 5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs. We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation.

  10. Morphology of the tracheobronchial tree and the route of the pulmonary artery in the fetal minke whale (Balaenoptera acutorostrata).

    Science.gov (United States)

    Kida, M Y

    1998-12-01

    Molecular and statistical studies support the close phylogenetic relation between Cetacea and Artiodactyla. The presence of the tracheal bronchus has been pointed out as one of the common traits between only these groups. Nakakuki (1980) has investigated the mammalian tracheobronchial trees in 50 species based on his new nomenclature, and his study has consequently demonstrated the above-mentioned indication. Therefore, comparative anatomy of the tracheobronchial tree based on the nomenclature seems to be useful for investigations of the cetacean phylogeny. Three pairs of fetal lungs of the minke whale (Balaenoptera acutorostrata) were supplied from the Institute of Cetacean Research, Tokyo (1991) to observe their tracheobronchial trees and the ramification of the pulmonary artery. The fetal tracheobronchial tree consisted of one tracheal, four lateral, four dorsal and one medial secondary bronchi in the right lung, and five or six lateral and four or five dorsal secondary bronchi in the left, using the new nomenclature. The right pulmonary artery crossed the right axial bronchus from the ventral side to the dorsal over the third lateral bronchus. The tracheal bronchus in the fetal minke whale seems to belong to the type II of Nakakuki's nomenclature, and this type is seen in one species of the river dolphins. The other conspicuous traits of the fetal lungs are the defect of the second lateral broncus and the route of the pulmonary artery in the right side. This route is very different from that of many other mammals.

  11. A critical role for Egr-1 during vascular remodelling in pulmonary arterial hypertension

    NARCIS (Netherlands)

    Dickinson, Michael G.; Kowalski, Piotr S.; Bartelds, Beatrijs; Borgdorff, Marinus A. J.; van der Feen, Diederik; Sietsma, Hannie; Molema, Grietje; Kamps, Jan A. A. M.; Berger, Rolf M. F.

    2014-01-01

    Aims Pulmonary arterial hypertension (PAH) is characterized by the development of unique neointimal lesions in the small pulmonary arteries, leading to increased right ventricular (RV) afterload and failure. Novel therapeutic strategies are needed that target these neointimal lesions. Recently, the

  12. Vascular endothelial-cadherin downregulation as a feature of endothelial transdifferentiation in monocrotaline-induced pulmonary hypertension.

    Science.gov (United States)

    Nikitopoulou, Ioanna; Orfanos, Stylianos E; Kotanidou, Anastasia; Maltabe, Violetta; Manitsopoulos, Nikolaos; Karras, Panagiotis; Kouklis, Panos; Armaganidis, Apostolos; Maniatis, Nikolaos A

    2016-08-01

    Increased pulmonary vascular resistance in pulmonary hypertension (PH) is caused by vasoconstriction and obstruction of small pulmonary arteries by proliferating vascular cells. In analogy to cancer, subsets of proliferating cells may be derived from endothelial cells transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within endothelial cells in PH, we injected rats with alkaloid monocrotaline to induce PH and measured lung tissue levels of endothelial-specific protein and critical differentiation marker vascular endothelial (VE)-cadherin. VE-cadherin expression by immonoblotting declined significantly 24 h and 15 days postinjection to rebound to baseline at 30 days. There was a concomitant increase in transcriptional repressors Snail and Slug, along with a reduction in VE-cadherin mRNA. Mesenchymal markers α-smooth muscle actin and vimentin were upregulated by immunohistochemistry and immunoblotting, and α-smooth muscle actin was colocalized with endothelial marker platelet endothelial cell adhesion molecule-1 by confocal microscopy. Apoptosis was limited in this model, especially in the 24-h time point. In addition, monocrotaline resulted in activation of protein kinase B/Akt, endothelial nitric oxide synthase (eNOS), nuclear factor (NF)-κB, and increased lung tissue nitrotyrosine staining. To understand the etiological relationship between nitrosative stress and VE-cadherin suppression, we incubated cultured rat lung endothelial cells with endothelin-1, a vasoconstrictor and pro-proliferative agent in pulmonary arterial hypertension. This resulted in activation of eNOS, NF-κB, and Akt, in addition to induction of Snail, downregulation of VE-cadherin, and synthesis of vimentin. These effects were blocked by eNOS inhibitor N(ω)-nitro-l-arginine methyl ester. We propose that transcriptional repression of VE-cadherin by nitrosative stress is involved in endothelial-mesenchymal transdifferentiation in experimental PH.

  13. Perturbed lignification impacts tree growth in hybrid poplar--a function of sink strength, vascular integrity, and photosynthetic assimilation.

    Science.gov (United States)

    Coleman, Heather D; Samuels, A Lacey; Guy, Robert D; Mansfield, Shawn D

    2008-11-01

    The effects of reductions in cell wall lignin content, manifested by RNA interference suppression of coumaroyl 3'-hydroxylase, on plant growth, water transport, gas exchange, and photosynthesis were evaluated in hybrid poplar trees (Populus alba x grandidentata). The growth characteristics of the reduced lignin trees were significantly impaired, resulting in smaller stems and reduced root biomass when compared to wild-type trees, as well as altered leaf morphology and architecture. The severe inhibition of cell wall lignification produced trees with a collapsed xylem phenotype, resulting in compromised vascular integrity, and displayed reduced hydraulic conductivity and a greater susceptibility to wall failure and cavitation. In the reduced lignin trees, photosynthetic carbon assimilation and stomatal conductance were also greatly reduced, however, shoot xylem pressure potential and carbon isotope discrimination were higher and water-use efficiency was lower, inconsistent with water stress. Reductions in assimilation rate could not be ascribed to increased stomatal limitation. Starch and soluble sugars analysis of leaves revealed that photosynthate was accumulating to high levels, suggesting that the trees with substantially reduced cell wall lignin were not carbon limited and that reductions in sink strength were, instead, limiting photosynthesis.

  14. A novel echocardiography formula for calculating predicted pulmonary vascular resistance in patients with mitral stenosis

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    Amiliana M. Soesanto

    2016-07-01

    Full Text Available Background: Pulmonary vascular resistance (PVR plays an important role in the natural history, prognosis, and outcome after valve intervention in patients with mitral stenosis (MS. The existing formula to estimate PVR by means of echocardiography is not readily applicable in the MS patient subset because it does not specifically calculate the risk of PVR in MS. The aim of this study was to find a new echocardiography formula to estimate PVR in MS.Methods: This diagnostic study was conducted in 2 stages. In the first stage, 58 consecutive subjects with MS were studied to find some model formulas for estimating PVR by multiple regression. Eight echo parameters were analyzed to seek their correlation with the invasive PVR value as a gold standard. The formula that had the best correlation and was easiest to use would be selected. In the second stage, those model formulas were validated by applying them to a further 34 consecutive MS subjects.Results: Four formulas which gave a discriminator coefficient of r2 0.62–0.68 were derived.  The best model formula was proposed for further application.  The new selected formula PVR=-7.465+3.566 TRvmax –(0.23 TVs’+6.799 (RV-MPI showed good correlation (r=0.71, p<0.001 to the invasive PVR value, with good reliability. TRvmax is maximal velocity of tricuspid regurgitation, TVs’ is systolic velocity of tricuspid annulus, and RV-MPI is right ventricle index myocardial performance. ROC curve showed that the cut off point 7.2 has good sensitivity and specificity (90% and 88%, respectively to predict PVR 7 WU.Conclusion: This study has shown that a novel echocardiography formula can estimate PVR with good correlation and reliability in subjects with mitral stenosis.

  15. Classification and regression tree (CART model to predict pulmonary tuberculosis in hospitalized patients

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    Aguiar Fabio S

    2012-08-01

    Full Text Available Abstract Background Tuberculosis (TB remains a public health issue worldwide. The lack of specific clinical symptoms to diagnose TB makes the correct decision to admit patients to respiratory isolation a difficult task for the clinician. Isolation of patients without the disease is common and increases health costs. Decision models for the diagnosis of TB in patients attending hospitals can increase the quality of care and decrease costs, without the risk of hospital transmission. We present a predictive model for predicting pulmonary TB in hospitalized patients in a high prevalence area in order to contribute to a more rational use of isolation rooms without increasing the risk of transmission. Methods Cross sectional study of patients admitted to CFFH from March 2003 to December 2004. A classification and regression tree (CART model was generated and validated. The area under the ROC curve (AUC, sensitivity, specificity, positive and negative predictive values were used to evaluate the performance of model. Validation of the model was performed with a different sample of patients admitted to the same hospital from January to December 2005. Results We studied 290 patients admitted with clinical suspicion of TB. Diagnosis was confirmed in 26.5% of them. Pulmonary TB was present in 83.7% of the patients with TB (62.3% with positive sputum smear and HIV/AIDS was present in 56.9% of patients. The validated CART model showed sensitivity, specificity, positive predictive value and negative predictive value of 60.00%, 76.16%, 33.33%, and 90.55%, respectively. The AUC was 79.70%. Conclusions The CART model developed for these hospitalized patients with clinical suspicion of TB had fair to good predictive performance for pulmonary TB. The most important variable for prediction of TB diagnosis was chest radiograph results. Prospective validation is still necessary, but our model offer an alternative for decision making in whether to isolate patients with

  16. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

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    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  17. A novel decision tree approach based on transcranial Doppler sonography to screen for blunt cervical vascular injuries.

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    Purvis, Dianna; Aldaghlas, Tayseer; Trickey, Amber W; Rizzo, Anne; Sikdar, Siddhartha

    2013-06-01

    Early detection and treatment of blunt cervical vascular injuries prevent adverse neurologic sequelae. Current screening criteria can miss up to 22% of these injuries. The study objective was to investigate bedside transcranial Doppler sonography for detecting blunt cervical vascular injuries in trauma patients using a novel decision tree approach. This prospective pilot study was conducted at a level I trauma center. Patients undergoing computed tomographic angiography for suspected blunt cervical vascular injuries were studied with transcranial Doppler sonography. Extracranial and intracranial vasculatures were examined with a portable power M-mode transcranial Doppler unit. The middle cerebral artery mean flow velocity, pulsatility index, and their asymmetries were used to quantify flow patterns and develop an injury decision tree screening protocol. Student t tests validated associations between injuries and transcranial Doppler predictive measures. We evaluated 27 trauma patients with 13 injuries. Single vertebral artery injuries were most common (38.5%), followed by single internal carotid artery injuries (30%). Compared to patients without injuries, mean flow velocity asymmetry was higher for single internal carotid artery (P = .003) and single vertebral artery (P = .004) injuries. Similarly, pulsatility index asymmetry was higher in single internal carotid artery (P = .015) and single vertebral artery (P = .042) injuries, whereas the lowest pulsatility index was elevated for bilateral vertebral artery injuries (P = .006). The decision tree yielded 92% specificity, 93% sensitivity, and 93% correct classifications. In this pilot feasibility study, transcranial Doppler measures were significantly associated with the blunt cervical vascular injury status, suggesting that transcranial Doppler sonography might be a viable bedside screening tool for trauma. Patient-specific hemodynamic information from transcranial Doppler assessment has the potential to alter

  18. Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes.

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    Régent, Alexis; Ly, Kim Heang; Lofek, Sébastien; Clary, Guilhem; Tamby, Mathieu; Tamas, Nicolas; Federici, Christian; Broussard, Cédric; Chafey, Philippe; Liaudet-Coopman, Emmanuelle; Humbert, Marc; Perros, Frédéric; Mouthon, Luc

    2016-10-01

    Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation.

  19. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

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    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

  20. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

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    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  1. Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation.

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    Agnoletti, Gabriella; Gala, Simona; Ferroni, Francesca; Bordese, Roberto; Appendini, Lorenzo; Pace Napoleone, Carlo; Bergamasco, Laura

    2017-06-01

    To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m(2). These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity. Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m(2), in adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m(2), and in adults from 2.8 (2.0-4.7) to 2.1 (1.8-2.8)WU*m(2). In 71% of patients, PVR fell to less than 2 WU*m(2). Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3) L/min/m(2), P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m(2), P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20) mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0-1.6) to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0) L/beat, P = .01. This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents. Copyright © 2017 The American Association for

  2. Chronic allergic inflammation causes vascular remodeling and pulmonary hypertension in BMPR2 hypomorph and wild-type mice.

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    Elizabeth M Mushaben

    Full Text Available Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2 gene have been identified in patients with heritable pulmonary arterial hypertension (PAH; however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT Balb/c/Byj mice were exposed to house dust mite (HDM allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations.

  3. [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

    Science.gov (United States)

    Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

  4. Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy.

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    Goo, Hyun Woo; Park, Sang Hyub

    2017-06-23

    Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy.

  5. Hypoxia-inducible factor-1 α/platelet derived growth factor axis in HIV-associated pulmonary vascular remodeling

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    Bartolome Sonja

    2011-08-01

    Full Text Available Abstract Background Human immunodeficiency virus (HIV infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH. Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF-1α and platelet-derived growth factor (PDGF, critical mediators implicated in the pathogenesis of HIV-PAH. Methods The lungs from 4-5 months old HIV-1 transgenic (Tg rats were assessed for the presence of pulmonary vascular remodeling and HIF-1α/PDGF-BB expression in comparison with wild type controls. Human primary pulmonary arterial endothelial cells (HPAEC were treated with HIV-associated proteins in the presence or absence of pretreatment with antioxidants, for 24 hrs followed by estimation of ROS levels and western blot analysis of HIF-1α or PDGF-BB. Results HIV-Tg rats, a model with marked viral protein induced vascular oxidative stress in the absence of active HIV-1 replication demonstrated significant medial thickening of pulmonary vessels and increased right ventricular mass compared to wild-type controls, with increased expression of HIF-1α and PDGF-BB in HIV-Tg rats. The up-regulation of both HIF-1α and PDGF-B chain mRNA in each HIV-Tg rat was directly correlated with an increase in right ventricular/left ventricular+septum ratio. Supporting our in-vivo findings, HPAECs treated with HIV-proteins: Tat and gp120, demonstrated increased ROS and parallel increase of PDGF-BB expression with the maximum induction observed on treatment with R5 type gp-120CM. Pre-treatment of endothelial cells with antioxidants or transfection of cells with HIF-1α small interfering RNA resulted in abrogation of gp-120CM mediated induction of PDGF-BB, therefore, confirming that ROS generation and

  6. Transforming growth factor-β plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma.

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    Tsujino, Kazuyuki; Reed, Nilgun Isik; Atakilit, Amha; Ren, Xin; Sheppard, Dean

    2017-01-01

    The efficacy and feasibility of targeting transforming growth factor-β (TGFβ) in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGFβ signaling in the Fra-2 Tg mice, we used a pan-TGFβ-blocking antibody, 1D11, and Tg mice in which TGFβ receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-Cre(ER);Tgfbr2(flox/flox)). Global inhibition of TGFβ by 1D11 did not ameliorate lung fibrosis histologically or biochemically, whereas it resulted in a significant increase in the number of immune cells infiltrating the lungs. In contrast, 1D11 treatment ameliorated the severity of pulmonary vascular remodeling in Fra-2 Tg mice. Similarly, genetic deletion of Tgfbr2 from smooth muscle cells resulted in improvement of pulmonary vascular remodeling in the Fra-2 Tg mice, as well as a decrease in the number of Ki67-positive vascular smooth muscle cells, suggesting that TGFβ signaling contributes to development of pulmonary vascular remodeling by promoting the proliferation of vascular smooth muscle cells. Deletion of Tgfbr2 from α-smooth muscle actin-expressing cells had no effect on fibrosis or inflammation in this model. These results suggest that efforts to target TGFβ in SSc will likely require more precision than simply global inhibition of TGFβ function. Copyright © 2017 the American Physiological Society.

  7. Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.

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    Imaura, Masaharu; Yokoyama, Haruko; Kohyama, Tomoki; Nagafuchi, Hiroyuki; Kohata, Yuji; Takahashi, Hiroyuki; Yamada, Yasuhiko

    2012-11-01

    Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. Seven patients were administered vancomycin intravenously and underwent extended hemodynamic monitoring with the PiCCO system in the intensive care unit (ICU) from April 2009 to March 2011. Vss was calculated using the Bayesian method, and the relationships of PVPI and EVLWI with Vss were investigated. The relationship between Vss/actual body weight (ABW) and median EVLWI on days when blood levels were measured was significant (r = 0.900, p = 0.0057), whereas the relationship between Vss/ABW and PVPI was not significant (r = 0.649, p = 0.1112). EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.

  8. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

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    Steven, Sebastian; Oelze, Matthias; Brandt, Moritz; Ullmann, Elisabeth; Kröller-Schön, Swenja; Heeren, Tjebo; Tran, Lan P.; Daub, Steffen; Dib, Mobin; Stalleicken, Dirk; Wenzel, Philip; Münzel, Thomas

    2017-01-01

    Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  9. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Sebastian Steven

    2017-01-01

    Full Text Available Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH. The role of the nitrovasodilator pentaerythritol tetranitrate (PETN on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v. in Wistar rats. Low (30 mg/kg; MCT30, middle (40 mg/kg; MCT40, or high (60 mg/kg; MCT60 dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d and reduced by oral PETN (10 mg/kg, 24 d therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1. PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1 in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  10. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension.

    Science.gov (United States)

    Steven, Sebastian; Oelze, Matthias; Brandt, Moritz; Ullmann, Elisabeth; Kröller-Schön, Swenja; Heeren, Tjebo; Tran, Lan P; Daub, Steffen; Dib, Mobin; Stalleicken, Dirk; Wenzel, Philip; Münzel, Thomas; Daiber, Andreas

    2017-01-01

    Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  11. Fractal Branching in Vascular Trees and Networks by VESsel GENeration Analysis (VESGEN)

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.

    2016-01-01

    Vascular patterning offers an informative multi-scale, fractal readout of regulatory signaling by complex molecular pathways. Understanding such molecular crosstalk is important for physiological, pathological and therapeutic research in Space Biology and Astronaut countermeasures. When mapped out and quantified by NASA's innovative VESsel GENeration Analysis (VESGEN) software, remodeling vascular patterns become useful biomarkers that advance out understanding of the response of biology and human health to challenges such as microgravity and radiation in space environments.

  12. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for α-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  13. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Goncharova Elena A

    2012-11-01

    Full Text Available Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH. The long-acting β2-adrenergic receptor (β2AR agonist formoterol, a racemate comprised of (R,R- and (S,S-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD. PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recent studies demonstrate that formoterol has anti-proliferative effects on airway smooth muscle cells and bronchial fibroblasts. The effects of formoterol and its enantiomers on PAVSM cell proliferation are not determined. The goals of this study were to examine effects of racemic formoterol and its enantiomers on PAVSM cell proliferation as it relates to COPD-associated PH. Methods Basal, thrombin-, PDGF- and chronic hypoxia-induced proliferation of primary human PAVSM cells was examined by DNA synthesis analysis using BrdU incorporation assay. ERK1/2, mTORC1 and mTORC2 activation were determined by phosphorylation levels of ERK1/2, ribosomal protein S6 and S473-Akt using immunoblot analysis. Results We found that (R,R and racemic formoterol inhibited basal, thrombin- and chronic hypoxia-induced proliferation of human PAVSM cells while (S,S formoterol had lesser inhibitory effect. The β2AR blocker propranolol abrogated the growth inhibitory effect of formoterol. (R,R, but not (S,S formoterol attenuated basal, thrombin- and chronic hypoxia-induced ERK1/2 phosphorylation, but had little effect on Akt and S6 phosphorylation levels. Formoterol and its enantiomers did not significantly affect PDGF-induced DNA synthesis and PDGF-dependent ERK1/2, S473-Akt and S6 phosphorylation in human PAVSM cells. Conclusions Formoterol inhibits basal, thrombin-, and chronic hypoxia-, but not PDGF-induced human PAVSM cell proliferation and ERK1/2, but has little effect on

  14. Trees

    Science.gov (United States)

    Al-Khaja, Nawal

    2007-01-01

    This is a thematic lesson plan for young learners about palm trees and the importance of taking care of them. The two part lesson teaches listening, reading and speaking skills. The lesson includes parts of a tree; the modal auxiliary, can; dialogues and a role play activity.

  15. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize pol...

  16. Vascular coupling induces synchronization, quasiperiodicity, and chaos in a nephron tree

    DEFF Research Database (Denmark)

    Marsh, D. J.; Sosnovtseva, Olga; Mosekilde, Erik;

    2007-01-01

    The paper presents a study of synchronization phenomena in a system of 22 nephrons supplied with blood from a common cortical radial artery. The nephrons are assumed to interact via hemodynamic and vascularly propagated coupling, both mediated by vascular connections. Using anatomic and physiolog......The paper presents a study of synchronization phenomena in a system of 22 nephrons supplied with blood from a common cortical radial artery. The nephrons are assumed to interact via hemodynamic and vascularly propagated coupling, both mediated by vascular connections. Using anatomic...... and physiological criteria, the nephrons are divided into groups: cortical nephrons and medullary nephrons with short, intermediate and long Henle loops. Within each of these groups the delay parameters of the internal feedback regulation are given a random component to represent the internephron variability....... For parameters that generate simple limit cycle dynamics in the pressure and flow regulation of single nephrons, the ensemble of coupled nephrons showed steady state, quasiperiodic or chaotic dynamics, depending on the interaction strengths and the arterial blood pressure. When the solutions were either...

  17. The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

    Science.gov (United States)

    Ghimire, Anukul; Andersen, Mads J; Burrowes, Lindsay M; Bouwmeester, J Christopher; Grant, Andrew D; Belenkie, Israel; Fine, Nowell M; Borlaug, Barry A; Tyberg, John V

    2016-12-01

    Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

  18. Peroxynitrite-mediated pulmonary vascular injury induced by endotoxin and protective role of cholecystokinin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this study we found: 1\\, There was endogenous ONOO- formation in lungs in the early stage of endotoxic shock. Exogenous ONOO- led to increase in microvascular permeability, severe lung pathological changes and enhanced MDA content. 2\\, It was, for the first time, found that responses of isolated pulmonary artery preincubated with ONOO- showed abnormal manifestations. (1) Low dose of ONOO- let to the inhibition of endothelial dependent relaxation, but enhacement of contractile response, both of which were similar to changes of reactivity in isolated pulmonary artery induced by LPS. (2) High dose of ONOO- reduced contractile response to PE and relaxation to SNP. 3\\, ONOO- had direct effect for relaxation of precontracted isolated pulmonary artery. The relaxing action of ONOO- was weak and was negtively regulated by endothelial cells, supporting the notion that ONOO- may be involved in pulmonary hypertension in the early stage of endotoxic shock. 4\\, It was, for the first time, found that LPS-induced increase in endogenous ONOO- generation in BPAEC and that endogenous ONOO- mediated injury to BPAEC induced by LPS, which may be a novel mechanism for endotoxin-elicited damage to endothelial cells. 5\\, Exposure of pulmonary artery to LPS led to reduction in endothelial dependent relaxation but enhancement in contractile response, both of which were reversed by concomitant exposure to CCK and LPS. 6\\, CCK protected cultured BPAEC against the detrimental effects of LPS such as lipoperoxide damages and cellular apoptosis as well as LPS-induced endogenous ONOO- formation. The underlying mechanism of CCK for cytoprotection may be mediated by its receptors and related to its reduced ability of endothelia to generate ONOO- induced by LPS.

  19. Nitric Oxide-Sensitive Pulmonary Hypertension in Congenital Rubella Syndrome

    Directory of Open Access Journals (Sweden)

    Francesco Raimondi

    2015-01-01

    Full Text Available Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP=40 mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement.

  20. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize...... between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease....... of female cancer or ischemic vascular disease. Genetic variation in genes coding for CYP1B1 and CYP2C9 enzymes have shown altered enzyme activity affecting levels of metabolites and thus potentially risk of disease. So far, however, findings have been inconsistent. Recently, large studies on the association...

  1. Increase of xylan synthetase activity during xylem differentiation of the vascular cambium of sycamore and poplar trees.

    Science.gov (United States)

    Dalessandro, G; Northcote, D H

    1981-01-01

    The activity of a β-(1-4)-xylan synthetase, a membrane-bound enzymic system, was measured in particulate enzymic preparations (1,000 g and 1,000-100,000 g pellets) obtained from homogenates of cambial cells, differentiating xylem cells and differentiated xylem cells isolated from actively growing trees of sycamore (Acer pseudoplatamus) and poplar (Populus robusta). The specific activity (nmol of xylan formed min(-1) mg(-1) of protein) as well as the activity calculated on a per cell basis (nmol of xylan formed min(-1) cell(-1)) of this enzymic system, markedly increased as cells differentiate from the vascular cambium to xylem. This increase is closely correlated with the enhanced deposition of xylan occurring during the formation of secondary thickening. The possible control of xylan synthesis during the biogenesis of plant cell wall is discussed.

  2. Dual-energy CT based vascular iodine analysis improves sensitivity for peripheral pulmonary artery thrombus detection: An experimental study in canines

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Han, Zong Hong; Zhou, Chang Sheng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Krazinski, Aleksander W.; Silverman, Justin R. [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

    2013-12-01

    Purpose: To evaluate the performance of dual-energy CT (DECT) based vascular iodine analysis for the detection of acute peripheral pulmonary thrombus (PE) in a canine model with histopathological findings as the reference standard. Materials and methods: The study protocol was approved by our institutional animal committee. Thrombi (n = 12) or saline (n = 4) were intravenously injected via right femoral vein in sixteen dogs, respectively. CT pulmonary angiography (CTPA) in DECT mode was performed and conventional CTPA images and DECT based vascular iodine studies using Lung Vessels application were reconstructed. Two radiologists visually evaluated the number and location of PEs using conventional CTPA and DECT series on a per-animal and a per-clot basis. Detailed histopathological examination of lung specimens and catheter angiography served as reference standard. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of DECT and CTPA were calculated on a segmental and subsegmental or more distal pulmonary artery basis. Weighted κ values were computed to evaluate inter-modality and inter-reader agreement. Results: Thirteen dogs were enrolled for final image analysis (experimental group = 9, control group = 4). Histopathological results revealed 237 emboli in 45 lung lobes in 9 experimental dogs, 11 emboli in segmental pulmonary arteries, 49 in subsegmental pulmonary arteries, 177 in fifth-order or more distal pulmonary arteries. Overall sensitivity, specificity, accuracy, PPV, and NPV for CTPA plus DECT were 93.1%, 76.9%, 87.8%, 89.4%, and 84.2% for the detection of pulmonary emboli. With CTPA versus DECT, sensitivities, specificities, accuracies, PPVs, and NPVs are all 100% for the detection of pulmonary emboli on a segmental pulmonary artery basis, 88.9%, 100%, 96.0%, 100%, and 94.1% for CTPA and 90.4%, 93.0%, 92.0%, 88.7%, and 94.1% for DECT on a subsegmental pulmonary artery basis; 23.8%, 96.4%, 50.4%, 93

  3. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    Science.gov (United States)

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  4. Vascular epiphytes and host trees of ant-gardens in an anthropic landscape in southeastern Mexico

    Science.gov (United States)

    Morales-Linares, Jonas; García-Franco, José G.; Flores-Palacios, Alejandro; Valenzuela-González, Jorge E.; Mata-Rosas, Martín; Díaz-Castelazo, Cecilia

    2016-12-01

    Ant-gardens (AGs) are considered one of the most complex mutualist systems between ants and plants, since interactions involving dispersal, protection, and nutrition occur simultaneously in them; however, little is known about the effects of the transformation of ecosystems on their diversity and interactions. In five environments with different land use within an anthropic landscape in southeastern Mexico, we investigated the diversity and composition of epiphytes and host trees of AGs built by Azteca gnava. A total of 10,871 individuals of 26 epiphytic species, associating with 859 AGs located in 161 host trees, were recorded. The diversity and composition of epiphytes tended to be different between environments; however, Aechmea tillandsioides and Codonanthe uleana were the most important species and considered true AG epiphytes, because they were the most frequent, abundant, and occurred exclusively in AGs. Other important species were the orchids Epidendrum flexuosum, Coryanthes picturata, and Epidendrum pachyrachis, and should also be considered true AG epiphytes, because they occurred almost exclusively in the AGs. The AG abundance in agroforestry plantations was similar or even greater than in riparian vegetation (natural habitat). The AGs were registered in 37 host species but were more frequent in Mangifera indica and Citrus sinensis. We conclude that true epiphytes of A. gnava AGs persist in different environments and host trees, and even these AGs could proliferate in agroforestry plantations of anthropic landscapes.

  5. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

    Science.gov (United States)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  6. Extreme nickel hyperaccumulation in the vascular tracts of the tree Phyllanthus balgooyi from Borneo.

    Science.gov (United States)

    Mesjasz-Przybylowicz, Jolanta; Przybylowicz, Wojciech; Barnabas, Alban; van der Ent, Antony

    2016-03-01

    Phyllanthus balgooyi (Phyllanthaceae), one of > 20 nickel (Ni) hyperaccumulator plant species known in Sabah (Malaysia) on the island of Borneo, is remarkable because it contains > 16 wt% Ni in its phloem sap, the second highest concentration of Ni in any living material in the world (after Pycnandra acuminata (Sapotaceae) from New Caledonia with 25 wt% Ni in latex). This study focused on the tissue-level distribution of Ni and other elements in the leaves, petioles and stem of P. balgooyi using nuclear microprobe imaging (micro-PIXE). The results show that in the stems and petioles of P. balgooyi Ni concentrations were very high in the phloem, while in the leaves there was significant enrichment of this element in the major vascular bundles. In the leaves, cobalt (Co) was codistributed with Ni, while the distribution of manganese (Mn) was different. The highest enrichment of calcium (Ca) in the stems was in the periderm, the epidermis and subepidermis of the petiole, and in the palisade mesophyll of the leaf. Preferential accumulation of Ni in the vascular tracts suggests that Ni is present in a metabolically active form. The elemental distribution of P. balgooyi differs from those of many other Ni hyperaccumulator plant species from around the world where Ni is preferentially accumulated in leaf epidermal cells.

  7. Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

    Science.gov (United States)

    Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

    2017-06-15

    The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel

  8. Relationship Between Pulmonary Artery Smooth Muscle Cells and Mechanism of Hypoxia-induced Pulmonary Vascular Remodeling%肺动脉平滑肌细胞与低氧性肺血管重塑形成机制

    Institute of Scientific and Technical Information of China (English)

    张凌云

    2013-01-01

    低氧条件下肺血管收缩、重塑,继而导致肺血管的持续对抗,其中以中膜增厚为主的肺血管重塑是导致低氧性肺动脉高压持续不可逆性病理改变的重要因素.肺动脉平滑肌细胞是肺动脉中膜的主要构成部分,慢性缺氧条件下由于各种活性介质及细胞生长因子稳态的失衡,肺动脉平滑肌细胞聚集、增殖、肥大及分泌胞外基质;另外,肺动脉平滑肌细胞通过各种信号通路与内膜的内皮细胞及外膜的成纤维细胞相互作用,在低氧性肺血管重塑过程中起着至关重要的作用,本文将对肺动脉平滑肌细胞与低氧性肺血管重塑形成机制的最新研究概况作一综述.%Under conditions of hypoxia generalized vasoconstriction and remodeling of the pulmonary vascular leads to pulmonary vascular persistent resistance. The medial thickening is the main reason of pulmonary vascular remodeling and hypoxic pulmonary artery hypertension, pulmonary artery smooth muscle cells (PASMC) are the principal structure of media, and chronic hypoxia induces the imbalance of vasoactive substances and growth factors. Under this condition, the main medial thickening is believed to be attributable to proliferation, hypertrophy and increased accumulation of PASMC as well as expression of extracellular matrix proteins. Moreover, PASMC has an interaction with endothelial cell of intima and fibroblast of adventitia through multiple signal pathways and plays a crucial role in the development of pulmonary vascular remodeling. The article will make a summary of latest research on PASMC and mechanism of hypoxic pulmonary vascular remodeling.

  9. Effect of chemoreceptor denervation on the pulmonary vascular response to atelectasis.

    Science.gov (United States)

    Levitzky, M G; Newell, J C; Dutton, R E

    1978-10-01

    Six dogs anesthetized with 30 mg/kg pentobarbital were ventilated after differential cannulation of the main stem bronchi. Following sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta (QT). Following 10 min of bilateral 100% O2, QL was 37.4 +/- 5.8% of QT. When left lung atelectasis was induced while the right lung remained on 100% O2, PaO2 remained above 75 mm Hg and QL fell to 26.1 +/- 5.0% of QT. However, when the right lung was ventilated with room air while the left lung remained atelectatic, PaO2 fell to 50.0 +/- 2.6 mm Hg and QL rose to 36.7 +/- 6.2% of QT. Six dogs which had undergone peripheral chemoreceptor denervation prior to these experiments showed a similar decrease in perfusion of the atelectatic left lung when the right lung was ventilated with 100% O2, but did not increase blood flow to the atelectatic lung during systemic hypoxemia. Thus, the increased blood flow to the atelectatic lung which occurs during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

  10. White Paper of the Society of Computed Body Tomography and Magnetic Resonance on Dual-Energy CT, Part 3: Vascular, Cardiac, Pulmonary, and Musculoskeletal Applications.

    Science.gov (United States)

    De Cecco, Carlo N; Schoepf, U Joseph; Steinbach, Lynne; Boll, Daniel T; Foley, W Dennis; Kaza, Ravi K; Bolus, David N; Morgan, Desiree E; Sahani, Dushyant V; Shuman, William P; Siegel, Marilyn J; Vrtiska, Terri J; Yeh, Benjamin M; Berland, Lincoln L

    2017-01-01

    This is the third of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its Task Force on dual-energy computed tomography. This paper, part 3, describes computed tomography angiography and thoracic, cardiac, vascular, and musculoskeletal clinical applications. At the end of the discussion of each application category (vascular, cardiac, pulmonary, and musculoskeletal), we present our consensus opinions on the current clinical utility of the application and opportunities for further research.

  11. Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Salonen Raimo O

    2005-03-01

    Full Text Available Abstract Background This study was performed within the scope of two multi-center European Commission-funded projects (HEPMEAP and PAMCHAR concerning source-composition-toxicity relationship for particulate matter (PM sampled in Europe. The present study aimed to optimize the design for PM in vivo toxicity screening studies in terms of dose and time between a single exposure and the determination of the biological responses in a rat model mimicking human disease resulting in susceptibility to ambient PM. Dust in thoracic PM size-range (aerodynamic diameter Results The neutrophil numbers in bronchoalveolar lavage fluid increased tremendously after exposure to the highest RTD doses or EHC-93. Furthermore, PM exposure slightly affected blood coagulation since there was a small but significant increase in the plasma fibrinogen levels (factor 1.2. Pulmonary inflammation and oxidative stress as well as changes in blood coagulation factors and circulating blood cell populations were observed within the range of 3 to 10 mg PM/kg of body weight without significant pulmonary injury. Conclusion The optimal dose for determining the toxicity ranking of ambient derived PM samples in spontaneously hypertensive rats is suggested to be between 3 and 10 mg PM/kg of body weight under the conditions used in the present study. At a lower dose only some inflammatory effects were detected, which will probably be too few to be able to discriminate between PM samples while a completely different response pattern was observed with the highest dose. In addition to the dose, a 24-hr interval from exposure to sacrifice seemed appropriate to assess the relative toxic potency of PM since the majority of the health effects were observed one day after PM exposure compared to the other times examined. The aforementioned considerations provide a good basis for conducting PM toxicity screening studies in spontaneously hypertensive rats.

  12. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    de Matthaeis A

    2014-05-01

    Full Text Available Angela de Matthaeis,1 Antonio Greco,2,* Mariangela Pia Dagostino,2 Giulia Paroni,2 Andrea Fontana,3 Manlio Vinciguerra,1,4,5 Gianluigi Mazzoccoli,1,* Davide Seripa,2 Gianluigi Vendemiale61Division of Internal Medicine and Chronobiology Unit, 2Geriatrics Unit and Gerontology, Geriatrics Research Laboratory, Department of Medical Sciences, 3Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, 4Euro-Mediterranean Institute of Sciences and Technology, Palermo, Italy; 5University College London, Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, London, UK; 6Geriatrics Unit, University of Foggia, Foggia, Italy*These authors contributed equally to this workAbstract: Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD, a common medical condition in the elderly. Flow-mediated dilation (FMD, a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1 and after (phase 2 standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001, pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001, pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001, FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001 and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001. FMD values were

  13. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance a

  14. Effects of Puerarin on Pulmonary Vascular Remodeling and Protein Kinase C-α in Chronic Cigarette Smoke Exposure Smoke-exposed Rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoxia ZHU; Yongjian XU; Hui ZOU; Zhenxiang ZHANG; Wang NI; Shixin CHEN

    2008-01-01

    In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-α (PKC-α) in chronic exposure smoke rats, 54 male Wistar rats were randomly di- vided into 7 groups: control group (C group), smoke exposure groups (S4w group, Saw group), puer- arin groups (P4w group, P8w group), propylene glycol control groups (PC4w group,PC8w group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puer- arin. To evaluate vascular remodeling, alpha-smooth muscle actin (α-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcrip- tion-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-α mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and α-SM-actin expres- sion were increased greatly, PASMC apoptosis was increased and proliferation was markedly in- creased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-ct mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the per- eentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-α mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an

  15. Trees

    OpenAIRE

    Henri Epstein

    2016-01-01

    An algebraic formalism, developed with V. Glaser and R. Stora for the study of the generalized retarded functions of quantum field theory, is used to prove a factorization theorem which provides a complete description of the generalized retarded functions associated with any tree graph. Integrating over the variables associated to internal vertices to obtain the perturbative generalized retarded functions for interacting fields arising from such graphs is shown to be possible for a large cate...

  16. Trees

    OpenAIRE

    Epstein, Henri

    2016-01-01

    An algebraic formalism, developped with V. Glaser and R. Stora for the study of the generalized retarded functions of quantum field theory, is used to prove a factorization theorem which provides a complete description of the generalized retarded functions associated with any tree graph. Integrating over the variables associated to internal vertices to obtain the perturbative generalized retarded functions for interacting fields arising from such graphs is shown to be possible for a large cat...

  17. Trees

    CERN Document Server

    Epstein, Henri

    2016-01-01

    An algebraic formalism, developped with V.~Glaser and R.~Stora for the study of the generalized retarded functions of quantum field theory, is used to prove a factorization theorem which provides a complete description of the generalized retarded functions associated with any tree graph. Integrating over the variables associated to internal vertices to obtain the perturbative generalized retarded functions for interacting fields arising from such graphs is shown to be possible for a large category of space-times.

  18. Idiopathic pulmonary fibrosis and collagen vascular diseases - high resolution CT findings; Pneumopatias intersticiais difusas idiopaticas e associadas a colagenoses - aspectos da tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira Neto, Armando Leao; Mogami, Roberto [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Centro Biomedico. Inst. de Radiologia; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. Biomedico. Dept. de Radiologia; Capone, Domenico [Universidade Estadual, Rio de Janeiro, RJ (Brazil). Dept. de Penumologia

    1996-09-01

    The aspects of the thorax high-resolution computed tomography of 15 patients with idiopathic pulmonary fibrosis and 11 patients with collagen vascular diseases are described and characterized mainly by the presence of reticular lesions with little cysts predominantly in the periphery and lower lobes. They may be associated with ground-glass lesions that, as usual, means areas of alveolitis. (author) 31 refs., 5 figs.

  19. Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation.

    Science.gov (United States)

    Ikutomi, Masayasu; Sahara, Makoto; Nakajima, Toshiaki; Minami, Yoshiyasu; Morita, Toshihiro; Hirata, Yasunobu; Komuro, Issei; Nakamura, Fumitaka; Sata, Masataka

    2015-09-01

    It is still controversial whether bone marrow (BM)-derived endothelial progenitor cells (EPCs) can contribute to vascular repair and prevent the progression of vascular diseases. We aimed to characterize BM-derived EPC subpopulations and to evaluate their therapeutic efficacies to repair injured vascular endothelium of systemic and pulmonary arteries. BM mononuclear cells of Fisher-344 rats were cultured under endothelial cell-conditions. Early EPCs appeared on days 3-6. Late-outgrowth and very late-outgrowth EPCs (LOCs and VLOCs) were defined as cells forming cobblestone colonies on days 9-14 and 17-21, respectively. Among EPC subpopulations, LOCs showed the highest angiogenic capability with enhanced proliferation potential and secretion of proangiogenic proteins. To investigate the therapeutic effects of these EPCs, Fisher-344 rats underwent wire-mediated endovascular injury in femoral artery (FA) and were concurrently injected intraperitoneally with 60mg/kg monocrotaline (MCT). Injured rats were then treated with six injections of one of three EPCs (1×10(6) per time). After 4weeks, transplanted LOCs, but not early EPCs or VLOCs, significantly attenuated neointimal lesion formation in injured FAs. Some of CD31(+) LOCs directly replaced the injured FA endothelium (replacement ratio: 11.7±7.0%). In contrast, any EPC treatment could neither replace MCT-injured endothelium of pulmonary arterioles nor prevent the progression of pulmonary arterial hypertension (PAH). LOCs modified protectively the expression profile of angiogenic and inflammatory genes in injured FAs, but not in MCT-injured lungs. BM-derived LOCs can contribute to vascular repair of injured systemic artery; however, even they cannot rescue injured pulmonary vasculature under MCT-induced PAH. Copyright © 2015. Published by Elsevier Ltd.

  20. Pulmonary vasculature in dogs assessed by three-dimensional fractal analysis and chemometrics

    DEFF Research Database (Denmark)

    Müller, Anna V; Marschner, Clara B; Kristensen, Annemarie T

    2017-01-01

    angiogram, applying fractal analyses of these vascular trees in dogs with and without diseases that are known to predispose to thromboembolism, and testing the hypothesis that diseased dogs would have a different fractal dimension than healthy dogs. A total of 34 dogs were sampled. Based on computed...... tomographic pulmonary angiograms findings, dogs were divided in three groups: diseased with pulmonary thromboembolism (n = 7), diseased but without pulmonary thromboembolism (n = 21), and healthy (n = 6). An observer who was aware of group status created three-dimensional pulmonary artery vascular trees...... for each dog using a semiautomated segmentation technique. Vascular three-dimensional reconstructions were then evaluated using fractal analysis. Fractal dimensions were analyzed, by group, using analysis of variance and principal component analysis. Fractal dimensions were significantly different among...

  1. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    Science.gov (United States)

    de Matthaeis, Angela; Greco, Antonio; Dagostino, Mariangela Pia; Paroni, Giulia; Fontana, Andrea; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Seripa, Davide; Vendemiale, Gianluigi

    2014-01-01

    Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium. PMID:24904207

  2. Functional high-resolution computed tomography of pulmonary vascular and airway reactions. Experimental results. Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefaess- und Atemwegsreaktionen

    Energy Technology Data Exchange (ETDEWEB)

    Herold, C.J. (Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria) Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology); Brown, R.H. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Physiology); Wetzel, R.C.; Herold, S.M. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine); Zeerhouni, E.A. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology)

    1993-03-01

    We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 [mu]m and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 [mu]m through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced broncho-constriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualized adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. (orig.).

  3. Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2:FiO2 Ratio Early After Major Burns.

    Science.gov (United States)

    Johansson, Joakim; Steinvall, Ingrid; Herwald, Heiko; Lindbom, Lennart; Sjöberg, Folke

    2015-01-01

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (PaO2:FiO2 < 27 kPa (P = .004). The authors have documented a correlation between dynamic change of blood leukocytes and pulmonary failure early after burns.

  4. Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Masato Kono

    Full Text Available BACKGROUND: The aim of this study was to evaluate the cumulative incidence and the predictive factors for collagen vascular disease (CVD in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF, and to examine the features of patients who then developed CVD. METHODS: This was a retrospective review of 111 consecutive patients with IPF diagnosed at our institution. None of the patients fulfilled any of the CVD criteria from the American College of Rheumatology (ACR within 6 months or more after the diagnosis of IPF. RESULTS: Ten patients (9.0% developed CVD during the follow-up period: four had rheumatoid arthritis (RA; four had microscopic polyangiitis (MPA; one had systemic sclerosis (SSc; and one had SSc and Sjogren's syndrome (SjS. The mean time until CVD diagnosis was 3.9 years. The cumulative incidences of CVD at 1, 5, and 10 years were 0.91%, 9.85%, and 15.5%, respectively. Patients who developed CVD were significantly younger, more likely to be women and had a better prognosis than those with IPF. Cox proportional hazards regression analysis showed that female sex and the presence of lymphoid aggregates with germinal centers were significantly associated with the occurrence of CVD in patients initially diagnosed with IPF. CONCLUSIONS: CVD is an important underlying condition in IPF, and shows better prognosis. The possibility of the development of CVD should remain a consideration in the follow-up of IPF.

  5. Pulmonary Hypertension in Elderly Patients with Diastolic Dysfunction and Preserved Ejection Fraction

    Science.gov (United States)

    Afshar, Majid; Collado, Fareed; Doukky, Rami

    2012-01-01

    Purpose: Patients with diastolic dysfunction may have a disproportionate degree of elevation in pulmonary pressure, particularly in the elderly. Higher pulmonary vascular resistance in the elderly patients with heart failure but preserved ejection fraction suggests that beyond the post-capillary contribution of pulmonary venous congestion, a pre-capillary component of pulmonary arterial hypertension occurs. We aim to identify if pulmonary vascular resistance in elderly patients with diastolic dysfunction is disproportionately higher than patients with systolic dysfunction independent of filling pressures. Methods: 389 patients identified retrospectively between 2003- 2010; elderly with preserved ejection fraction, elderly with depressed ejection fraction, and primary arterial hypertension who underwent right-heart catheterization at Rush University. Results: No significant difference in pulmonary vascular resistance between systolic and diastolic dysfunction. The mean difference in pulmonary vascular resistance was not statistically significant at 0.40 mmHg·min/l (95% CI -3.03 to 3.83) with similar left ventricular filling pressures with mean difference of 3.38 mmHg (95% CI, -1.27 to 8.02). When adjusted for filling pressures, there remained no difference in pulmonary vascular resistance for systolic and diastolic dysfunction. The mean pulmonary vascular resistance is more elevated in systolic heart failure compared to diastolic heart failure with means 3.13 mmHg·min/l and 3.52 mmHg·min/l, respectively. Conclusion: There was no other association identified for secondary pulmonary hypertension other than diastolic dysfunction and chronic venous pulmonary hypertension. Our results argue against any significant arterial remodeling that would lead to disproportionate pre-capillary hypertension, and implies that treatment should focus on lowering filling pressure rather than treating the pulmonary vascular tree. PMID:22282715

  6. Estimation of cardiac output and pulmonary vascular resistance by contrast echocardiography transit time measurement: a prospective pilot study.

    Science.gov (United States)

    Choi, Brian G; Sanai, Reza; Yang, Benjamin; Young, Heather A; Mazhari, Ramesh; Reiner, Jonathan S; Lewis, Jannet F

    2014-10-31

    Studies with other imaging modalities have demonstrated a relationship between contrast transit and cardiac output (CO) and pulmonary vascular resistance (PVR). We tested the hypothesis that the transit time during contrast echocardiography could accurately estimate both CO and PVR compared to right heart catheterization (RHC). 27 patients scheduled for RHC had 2D-echocardiogram immediately prior to RHC. 3 ml of DEFINITY contrast followed by a 10 ml saline flush was injected, and a multi-cycle echo clip was acquired from the beginning of injection to opacification of the left ventricle. 2D-echo based calculations of CO and PVR along with the DEFINITY-based transit time calculations were subsequently correlated with the RHC-determined CO and PVR. The transit time from full opacification of the right ventricle to full opacification of the left ventricle inversely correlated with CO (r=-0.61, p<0.001). The transit time from peak opacification of the right ventricle to first appearance in the left ventricle moderately correlated with PVR (r=0.46, p<0.01). Previously described echocardiographic methods for the determination of CO (Huntsman method) and PVR (Abbas and Haddad methods) did not correlate with RHC-determined values (p = 0.20 for CO, p = 0.18 and p = 0.22 for PVR, respectively). The contrast transit time method demonstrated reliable intra- (p<0.0001) and inter-observer correlation (p<0.001). We describe a novel method for the quantification of CO and estimation of PVR using contrast echocardiography transit time. This technique adds to the methodologies used for noninvasive hemodynamic assessment, but requires further validation to determine overall applicability.

  7. Measurement uncertainty in pulmonary vascular input impedance and characteristic impedance estimated from pulsed-wave Doppler ultrasound and pressure: clinical studies on 57 pediatric patients.

    Science.gov (United States)

    Tian, Lian; Hunter, Kendall S; Kirby, K Scott; Ivy, D Dunbar; Shandas, Robin

    2010-06-01

    Pulmonary vascular input impedance better characterizes right ventricular (RV) afterload and disease outcomes in pulmonary hypertension compared to the standard clinical diagnostic, pulmonary vascular resistance (PVR). Early efforts to measure impedance were not routine, involving open-chest measurement. Recently, the use of pulsed-wave (PW) Doppler-measured velocity to non-invasively estimate instantaneous flow has made impedance measurement more practical. One critical concern remains with clinical use: the measurement uncertainty, especially since previous studies only incorporated random error. This study utilized data from a large pediatric patient population to comprehensively examine the systematic and random error contributions to the total impedance uncertainty and determined the least error prone methodology to compute impedance from among four different methods. We found that the systematic error contributes greatly to the total uncertainty and that one of the four methods had significantly smaller propagated uncertainty; however, even when this best method is used, the uncertainty can be large for input impedance at high harmonics and for the characteristic impedance modulus. Finally, we found that uncertainty in impedance between normotensive and hypertensive patient groups displays no significant difference. It is concluded that clinical impedance measurement would be most improved by advancements in instrumentation, and the best computation method is proposed for future clinical use of the input impedance.

  8. 7A.03: TRANSGENERATIONAL INHERITANCE OF GENOME-WIDE DNA METHYLATION PROFILES IN PULMONARY VASCULAR ENDOTHELIAL DYSFUNCTION FOLLOWING EXTRAUTERINE GROWTH RESTRICTION.

    Science.gov (United States)

    Zhang, L; Du, L; Tang, L; Lao, L; Hu, Q

    2015-06-01

    Early postnatal life is considered as a critical time window for determination of long-term metabolic states and organ functions. Extrauterine growth restriction (EUGR) causes the development of adult onset chronic diseases, including pulmonary hypertension (PH). However, the mechanisms involved and the possibilities of transgenerational transmission on pulmonary vascular consequences in later life are still unclear. Epigenetic information can be inherited and represents a plausible transgenerational carrier of environmental information. Our study was designed to test whether epigenetics dysregulation mediates the cellular memory of this early postnatal event.(Figure is included in full-text article.) : To test this hypothesis, the EUGR pups were established by undernutritional until weaning. We isolated pulmonary vascular endothelial cells (PVEC) by magnetic-activated cell sorting (MACS) from EUGR and control rats. MeDIP-chip (Methyl-DNA immune precipitation chip), genome-scale mapping studies to search for differentially methylated loci. A postnatal insult, nutritional restriction-induced EUGR caused development of an increased PH at 9-week of age in male rats (First-generation of EUGR, F1-EUGR male). We intercrossed female adult control and F1-EUGR-male rats to obtain the second-generation (F2) offspring in two groups: C male-C female, EUGR-male -C-female. We found that significantly decreased pulmonary artery pressure in F2 female offspring in EUGR-male-C-female group (F2-EUGR-female), compared with controls to some degrees. we carried out genome-wide DNA methylation profiles screen for genes in rats between F1-EUGR-male and F2-EUGR-female. The EUGR and control group comparisons revealed consistently and distinctively methylated loci, with 74.8% F1-EUGR-male group and 84.5% F2-EUGR-female group changes in hyper-methylation loci enriched for highly significant group differences. Gene ontology (GO) analysis on no consistent differentially methylated genes

  9. Interactions among Vascular-Tone Modulators Contribute to High Altitude Pulmonary Edema and Augmented Vasoreactivity in Highlanders

    Science.gov (United States)

    Ali, Zahara; Mishra, Aastha; Kumar, Rahul; Alam, Perwez; Pandey, Priyanka; Ram, Rekhbala; Thinlas, Tashi; Mohammad, Ghulam; Pasha, M. A. Qadar

    2012-01-01

    Background The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f). Methodology/Principal Findings All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO2) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO2 inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p≤0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p≤0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05). Conclusions/Significance The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners. PMID:22984459

  10. Interactions among vascular-tone modulators contribute to high altitude pulmonary edema and augmented vasoreactivity in highlanders.

    Directory of Open Access Journals (Sweden)

    Zahara Ali

    Full Text Available BACKGROUND: The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE in HAPE-patients (HAPE-p and adaptation in highland natives (HLs; both in comparison to HAPE-free sojourners (HAPE-f. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO(2 and mean arterial pressure (MAP and biochemical parameters like, asymmetric dimethylarginine (ADMA, serotonin (5-HT, 8-iso-prostaglandin F2α (8-isoPGF2α, endothelin-1 (ET-1, plasma renin activity (PRA, plasma aldosterone concentration (PAC, superoxide dismutase (SOD and nitric oxide (NO in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p0.05 lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO(2 inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009. MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p ≤ 0.004. A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001, whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p ≤ 0.004, with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01 and with 5-HT in HLs (p = 0.05. CONCLUSIONS/SIGNIFICANCE: The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.

  11. Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

    Science.gov (United States)

    Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

    2006-01-01

    Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

  12. 缺氧性肺动脉高压新生大鼠肺血管重塑的研究%Pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    桑葵; 周英; 李明霞

    2012-01-01

    Objective To study the changes of pulmonary vascular remodeling in the pathogenesis of hypoxia-induced pulmonary hypertension ( HPH) in neonatal rats. Methods Ninety-six newborn Wistar rats were randomly divided into an HPH group (hypoxia exposure) and a control group (room air exposure). The mean pulmonary arteria pressure (mPAP) , right ventricle hypertrophy index ( RVHI) , and vascular remodeling indexes MT% and MA% were measured 3, 5, 7, 10, 14 and 21 days after exposure (re =8 each time point). The ultrastructure of pulmonary vascular was observed under a transmission electron microscope. Results mPAP in the HPH group 3,5,7, 10, 14 and 21 days after hypoxia exposure increased compared with the control group ( P < 0. 05). With the prolonged hypoxia time, mPAP in the HPH group increased more significantly. MT% , MA% and RVHI increased significantly in the HPH group after 7 days of hypoxia exposure in a time-dependent manner compared with the control group (P<0. 05). The transmission electron microscopy demonstrated that small pulmonary arterials became thickened, endothelial cell hyperplasia and degeneration, and organelles increased in the HPH group after 7 days of hypoxia exposure. Besides, collagen deposition in the extracellular matrix and the changes of pulmonary vascular remodeling were observed. Conclusions mPAP increases between 3 and 5 days of hypoxia exposure, resulting from pulmonary vascular spasm caused by hypoxia. After hypoxia of 7 days, the mPAP increases more significantly, pulmonary vascular remodeling occurs, and right ventricle becomes irreversibly hypertrophic. These changes may be intensified as the prolonged hypoxia time.%目的 通过建立新生大鼠缺氧性肺动脉高压(hypoxia-induced pulmonary hypertension,HPH)模型,探讨HPH新生大鼠发病过程中肺血管重塑的变化.方法 将96只新生Wistar大鼠随机分为2组:缺氧组和常氧对照组,缺氧组建立新生大鼠HPH模型.分别于缺氧3、5、7、10、14、21

  13. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    Science.gov (United States)

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion

  14. Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

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    Julien Guihaire

    2015-01-01

    Full Text Available Background. The epidemiology of pulmonary hypertension (PH is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg. After 28 days, right ventricular (RV remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.

  15. [Effects of feixin decoction on the contents of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the rat model of hypoxic pulmonary hypertension].

    Science.gov (United States)

    He, Hong-Jun; Dai, Ai-Guo

    2012-05-01

    To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH. Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water (at 30 mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at 28 g/kg) and Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure (mPAP) was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area (WA%) was determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique. Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly increased in the model group (P model group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05). FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.

  16. Mechanisms responsible for pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH).

  17. Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

    Science.gov (United States)

    Mandell, Erica; Powers, Kyle N; Harral, Julie W; Seedorf, Gregory J; Hunter, Kendall S; Abman, Steven H; Dodson, R Blair

    2015-12-15

    High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

  18. Análise da remodelação vascular na isquemia pulmonar experimental, nas fases aguda e crônica Analysis of acute and chronic vascular remodeling in an experimental model of pulmonary ischemia

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    Wanderley M. Bernardo

    2005-02-01

    pulmonary circulation characterize the vascular remodeling process and are likely correlated with local variations in flow and ischemia. OBJECTIVE: To define the histological alterations to the pulmonary circulation seen after experimentally-induced ischemia of the pulmonary artery and to correlate those alterations with known patterns of blood redistribution and vascular remodeling. METHOD: Wistar rats (n = 48 were randomized into two groups with ligation of the pulmonary artery and without (controls and were sacrificed on post-ischemia days 1, 7, 30 and 60. Lungs were removed and inspected for signs of parenchymal injury. External diameters, as well as wall thicknesses in the pulmonary, alveolar and bronchial end arterioles, were measured. Internal diameter and wall thickness percentage were calculated. RESULTS: Infarction, necrosis and hemorrhage occurred only in ischemic lungs. In nonischemic lungs, there was a sustained increase in the internal and external arteriolar diameters, with an initial reduction in wall thickness on day 1, and day-60 values were similar to those seen in controls. In ischemic lungs, there was a transitory reduction in the internal and external diameters of the pulmonary and bronchial end arterioles, together with an initial, equally transitory, increase in their wall thickness. The alveolar arterioles presented sustained and progressive increases in external diameter and wall thickness, with concomitant reductions in internal diameter. CONCLUSION: This model mimics distal arterial disease in patients with chronic pulmonary thromboembolism. The vascular response in nonischemic lungs was consistent with a pattern of flow remodeling, whereas that seen in ischemic lungs was more consistent with flow and ischemia. In the pulmonary and bronchial end arterioles, the response was transitory, in contrast to the sustained and progressive response seen in the alveolar arterioles, which was probably caused by delayed local flow.

  19. Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density

    Institute of Scientific and Technical Information of China (English)

    BAI Rong-jie; CHENG Xiao-guang; QU Hui; SHEN Bao-zhong; HAN Ming-jun; WU Zhen-hua

    2009-01-01

    Background The solitary pulmonary nodule (SPN) is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density (MVD) and vascular endothelial growth factors (VEGF) in SPNs using multi-slice computed tomography (MSCT); and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features.Also, the study called for the discussion of the method's clinical application value in the differential diagnosis of benign and malignant SPNs.Methods Sixty-eight patients with SPN underwent multi-location dynamic contrast enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s) MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves (TDC) and the peak height of the aorta. The quantitative parameters (perfusion, peak height, ratio of peak height of the SPN to that of the aorta) of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry.Results The perfusion peak heights of malignant ((96.15±11.55) HU) and inflammatory ((101.15±8.41) HU) SPNs were significantly higher than those of benign ((47.24±9.15) HU) SPNs (P<0.05, P<0.05). Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs (P<0.05, P<0.05). No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs (P>0.05, P>0.05). The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs (P<0.05).Perfusion values

  20. The clinical application of pulmonary vascular permeability index on differential diagnosis of acute pulmonary edema%肺血管通透性指数对急性肺水肿鉴别诊断价值初探

    Institute of Scientific and Technical Information of China (English)

    杨从山; 谢剑锋; 莫敏; 刘松桥; 黄英姿; 邱海波; 杨毅

    2011-01-01

    目的 探讨肺血管通透性指数(PVPI)在急性肺水肿鉴别诊断中的价值.方法 选2004年5月至2008年9月收住东南大学附属中大医院重症医学科,留置脉搏指示连续心排血量(PiCCO)导管,氧合指数[PaO2/吸入氧浓度(FiO2)]<300 mm Hg(1 mm Hg=0.133 kPa)且血管外肺水指数(EVLWI)≥7 ml/kg的急性肺水肿患者,分为急性肺损伤(ALI)组和心源性肺水肿组,观察PVPI、胸腔内血容量指数(ITBVI)、肺血容量(PBV)、血管外肺水(EVLW)/胸腔内血容量(ITBV)在2组中的变化与差异.结果 (1)34例患者纳入研究,其中ALI 22例,心源性肺水肿12例;(2)ALI组PVPI为2.7±1.4,心源性肺水肿组为1.9±0.6,2组比较,P<0.05.EVLWI、ITBVI在2组间差异无统计学意义(P>0.05);(3)PVPI与EVLWI呈正相关(r=0.762,P=0.000),与PaO2/FiO2呈负相关(r=-0.478,P=0.012);(4)纳入患者中肺内原因ARDS 8例,肺外原因ARDS 5例,肺外原因ARDS患者PVPI、EVLW/ITBV和EVLWI显著高于肺内原因ARDS患者.结论 PVPI有助于对重症患者肺水肿类型的鉴别.%Objective To assess the value of pulmonary vascular permeability index in differentiating acute lung injury (ALI) from cardiac pulmonary edema. Methods Critically ill patients with acute pulmonary edema were included from May, 2004 to September, 2008. Patients were divided into two groups, the ALI group and the cardiac pulmonary edema group (C group). Pulmonary vascular permeability index (PVPI) , intrathoracic blood volume (ITBVI) were determined by pulse indicator continuous cardiac output(PiCCO) system. Results ( 1 ) Thirty-four patients were enrolled, 22 cases in ALI group and 12 cases in C group. (2) The PVPI in patients of ALI group (2.7 ± 1.4) was higher than that of C group (1.9 ±0.6 ;P<0.05). EVLWI and ITBVI did not have the significant difference between the two groups (P >0. 05). (3) PVPI was positively correlated with EVLWI(r = 0. 762) , negatively correlated with PaO2/ FiO2(r= -0.478). (4)ARDS was diagnosed

  1. The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

    Institute of Scientific and Technical Information of China (English)

    甄国华; 张珍祥; 徐永健

    2003-01-01

    We investigated the expression of heme oxygenase-1 (HO-l) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin on the expression of HO-1 gene and pulmonary hypertension. A rat model of hypoxic pulmonary hypertension was recreated by exposure to intermittent normobaric hypoxic environment (10 % O2 ). Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the level of HO-1 mRNA in the rat lung tissue and double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood. Cardiac catheterization was employed to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathological changes of the intra-acinar pulmonary arteries (IAPA). It was found that (1) There was a low level of HO-1 mRNA in normal rat lung tissue, but the level of HO-1 mRNA increased by 2-4 times in the lung tissue of hypoxic rats (P<0.01). The quantity of COHb was 2-3 times those of control group (P<0.01or P<0. 05). These were accompanied by the increased of RVSP and the thickened IAPA; (2) Hemin could keep the HO-1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, thereby ameliorating the pathological changes of IAPA.In conclusion, the upregulation of the expression of HO-1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension.

  2. Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

    Science.gov (United States)

    Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

  3. Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

    Science.gov (United States)

    Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

  4. Biventricular failure with low pulmonary vascular resistance was managed by left ventricular assist device alone without right-sided mechanical support.

    Science.gov (United States)

    Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Hatano, Masaru; Kinoshita, Osamu; Nawata, Kan; Ono, Minoru

    2015-09-01

    How to manage preoperative right ventricular dysfunction (RVD) in heart failure patients without cardiogenic shock remains as a matter to be debated because implantable biventricular assist device treatment has not been established thus far. We here presented a patient with significant RVD indicated by low RV stroke work index (0.3 g/m) and RV dilatation as well as low pulmonary vascular resistance (PVR, 0.8 Wood Unit), who was managed by the introduction of pimobendan and sildenafil after the implantation of DuraHeart and tricuspid annuloplasty without right VAD, although his New York Heart Association symptom remained class III. Preoperative low PVR may be a key for successful LVAD treatment alone without right VAD in patients with INTERMACS profile 3 suffering RVD.

  5. Radioimmunotherapy Using Vascular Targeted 213Bi: The Role of TNF-Alpha in the Development of Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Davis, I.A.; Kennel, S.J.

    1998-10-14

    A monoclonal antibody (201B) specific to murine thrombomodulin, covalently linked to CHX-b-DTPA, successfully delivers chelated 213Bi, an {alpha}-particle emitter, (213Bi-201B) rapidly to lungvascular endothelium. When injected at doses of l MBq/mouse, 213Bi-201B destroyed most of the 100 colonies of EMT-6 mammary carcinomas growing as lung tumors of up to 2000 cells/colony. Some mice were cured of lung tumors and others had extended life-spans compared to untreated control animals but eventually succumbed to tumor recurrence. At injected doses of 4-6 MBq/mouse, 100% of lung tumor colonies were eliminated; however, 3-4 months later these mice developed pulmonary fibrosis and died. The mechanisms leading to the fibrotic response in other pulmonary irradiation models strongly implicate tumor necrosis factor-alpha (TNF-{alpha}), released from damaged tissues, as the pivotal inflammatory cytokine in a cascade of events which culminate in fibrosis. Attempts to prevent the development of pulmonary fibrosis, by using antibodies or soluble receptor (Enbrel{trademark}) as inhibitors of TNF-{alpha}, were unsuccessful. Additionally, mice genetically deficient for TNF-{alpha} production developed pulmonary fibrosis following 213Bi-201B treatment. Interestingly, non-tumor bearing BALB/c mice receiving Enbrel{trademark} or mice genetically deficient in TNF-{alpha} production and treated with 213Bi-201B, had significantly reduced life spans compared to mice receiving no treatment or 213Bi-201B alone. We speculate that, in normal mice, while TNF-{alpha} may induce an inflammatory response following {alpha}-particle radiation mediated tumor clearance and pulmonary damage, its effects in the post-tumor clearance time period may actually retard the development of fibrosis.

  6. Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension

    Institute of Scientific and Technical Information of China (English)

    Shunhou He; Qing Li; Sen Chen; Qingxiu Wang

    2007-01-01

    BACKGROUND: At present, inhalation of nitrogen monoxidum (NO) or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide (BE-CGRP) and nitricoxide synthase (NOS) in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension.OBJECTIVE: To observe the effects of stellate block on calcitonin gene-related peptide (CGRP) of vasodilation factors, prostacyclin, endothelin-1 of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase (BE-NOS) and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension.DESIGN: Randomly controlled animal study.SETTING: Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College.MATERIALS: A total of 24 adult Japanese rabbits of both genders and weighing 2.3 - 2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system (Leica-Q500IW) was made in Germany.METHODS: The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002, ① Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition,one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block

  7. Serum angiopoietin-like protein 3 levels: possible correlation with progressive skin sclerosis, digital ulcers and pulmonary vascular involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Aozasa, Naohiko; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Sumida, Hayakazu; Kuwano, Yosihiro; Yanaba, Koichi; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

    2014-03-01

    Angiopoietin-like protein 3 (ANGPTL3), which is part of a family of secreted glycoproteins that are structurally similar to angiopoietins, is principally expressed in the liver and is involved in lipid metabolism and angiogenesis. The aim of this study was to determine the clinical significance of serum ANGPTL3 levels, measured with a specific enzyme-linked immunosorbent assay, in patients with systemic sclerosis. Serum ANGPTL3 levels correlated positively with skin score in diffuse cutaneous systemic sclerosis with a disease duration ≤ 6 years. Furthermore, the prevalence of digital ulcers was significantly higher in patients with elevated serum ANGPTL3 levels than in other patients. Moreover, among patients excluding diffuse cutaneous systemic sclerosis with disease duration ≤ 6 years, serum ANGPTL3 levels correlated positively with estimated right ventricular systolic pressure. In conclusion, ANGPTL3 may contribute to the development of progressive skin sclerosis and proliferative obliterative vasculopathy, such as digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, in systemic sclerosis.

  8. Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Jalpa Kotecha

    2016-09-01

    Full Text Available Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF. Vascular endothelial growth factor (VEGF concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months. Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

  9. Novel echocardiographic approach to the accurate measurement of pulmonary vascular resistance based on a theoretical formula in patients with left heart failure -- pilot study.

    Science.gov (United States)

    Kanda, Takashi; Fujita, Masashi; Iida, Osamu; Masuda, Masaharu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Shiraki, Tatsuya; Takahara, Mitsuyoshi; Sakata, Yasushi; Uematsu, Masaaki

    2015-01-01

    Several non-invasive methods for measuring pulmonary vascular resistance (PVR) have been proposed to date, but they remain empirical, lacking sufficient accuracy to be used in clinical practice. The aims of this study were to propose a novel echocardiographic measurement of PVR based on a theoretical formula and investigate the feasibilty and accuracy of this method in patients with heart failure. Echocardiography was performed in 27 patients before right heart catheterization. Peak tricuspid regurgitation pressure gradient (TRPG), pulmonary regurgitation pressure gradient in end-diastole (PRPGed), and cardiac output derived from the time-velocity integral and the diameter in the left ventricular outflow tract (COLVOT) were measured. PVR based on a theoretical formula (PVRtheo) was calculated as (TRPG-PRPGed)/3COLVOTin Wood units (WU). The results were compared with PVR obtained by right heart catheterization (PVRcath) using linear regression and Bland-Altman analysis. Mean PVRcathwas 2.4±1.4 WU. PVRtheocorrelated well with PVRcath(r=0.83, P<0.001). On Bland-Altman analysis the mean difference was 0.1±0.7 WU. The limits of agreements were smaller than for other non-invasive estimations previously reported. The new echocardiographic approach based on a theoretical formula provides a non-invasive and accurate assessment of PVR in patients with heart failure.

  10. Initial Experience with Sildenafil, Bosentan, and Nitric Oxide for Pediatric Cardiomyopathy Patients with Elevated Pulmonary Vascular Resistance before and after Orthotopic Heart Transplantation

    Directory of Open Access Journals (Sweden)

    Babak Daftari

    2010-01-01

    Full Text Available Background. Although pulmonary hypertension complicating dilated cardiomyopathy has been shown to be a significant risk factor for graft failure after heart transplantation, the upper limits of pulmonary vascular resistance (PVR that would contraindicate pediatric heart transplantation are not known. Methods. A retrospective review of all pediatric orthotopic heart transplant (OHT performed at our institution from 2002 to 2007 was performed. Seven patients with PVR >6 Wood's units (WU prior to transplant were compared pre- and postoperatively with 20 matched controls with PVR <6 WU. All pulmonary vasodilator therapies used are described as well as outcomes during the first year posttransplant. Results. The mean PVR prior to transplantation in the 7 study cases was 11.0±4.6 (range 6–22 WU, compared to mean PVR of 3.07±0.9 WU (0.56–4.5 in the controls (=.27×10−6. All patients with elevated PVR were treated pre-OHT with either Sildenafil or Bosentan. Post-OHT, case patients received a combination of sildenafil, iloprost, and inhaled nitric oxide. All 7 case patients survived one year post-OHT, and there was no statistical difference between cases and controls for hospital stay, rejection/readmissions, or graft right ventricular failure. Mean PVR in the cases at one and three months post-OHT was not significantly different between the two groups. Only one of the cases required prolonged treatment with iloprost after OHT. Conclusions. A PVR above 6 WU should not be an absolute contraindication to heart transplantation in children.

  11. Reliability of Doppler-Based Measurement of Pulmonary Vascular Resistance in Congenital Heart Disease with Left-to-Right Shunt Lesions.

    Science.gov (United States)

    Bhyravavajhala, Srinivas; Velam, Vanajakshamma; Polapragada, Nishanth V; Pallempati, Pranav; Iragavarapu, Tammi Raju; Patnaik, Amar Narayan; Damera, Seshagiri Rao

    2015-06-01

    Pulmonary vascular resistance (PVR) is a crucial parameter in the management of patients with left-to-right shunt lesions. Cardiac catheterization (Cath) is the gold standard test to assess PVR (PVRcath ), but it is invasive and hence, risky in children with pulmonary arterial hypertension (PAH). A noninvasive tool to assess PVR is desirable. Ratio of tricuspid regurgitation velocity (TRV) and time-velocity integral of right ventricular outflow tract (TVIRVOT ) by Doppler was previously shown to be a reliable noninvasive method for estimation of PVR in acquired PAH. Peak TR velocity and TVIRVOT were recorded from 63 prospective patients with various congenital shunt lesions. Subsequently, the patients were subjected to cath in less than 2 hours. The patients were subdivided into four subsets based on age and pulmonary arterial mean pressure (PAMP). A regression equation was developed for calculation of PVR from TRV/TVIRVOT (PVREcho ) which was indexed for BSA (PVRIEcho ). Bland-Altman analysis was done for agreement between PVRIcath and PVRIEcho . Receiver operating characteristic (ROC) curves were plotted to test the identity of the two methods and also the applicability of PVRIEcho across a wide range of Wood units. Receiver operating characteristic curve plotted between the two methods showed good identity. Bland-Altman analysis showed excellent agreement between the two methods with negligible bias. ROC curves showed that PVRIEcho was accurate in distinguishing different cutoff values of PVR in each of the 4 groups. Noninvasive Doppler estimation of PVR is reliable in patients with shunt lesions over a wide range of PVR. © 2014, Wiley Periodicals, Inc.

  12. Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery

    NARCIS (Netherlands)

    S. Tuinman (Sietske); A.D. Cornet (Alexander); M.T. Kuipers (Maria); A.P.J. Vlaar (Alexander); M.J. Schultz (Marcus); A. Beishuizen (Auke); A.B.J. Groeneveld (Johan); N.P. Juffermans (Nicole)

    2013-01-01

    textabstractBackground: Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE).Methods: In two university hospital intensive care units, circulating sRAGE was measure

  13. Vascular rings.

    Science.gov (United States)

    Backer, Carl L; Mongé, Michael C; Popescu, Andrada R; Eltayeb, Osama M; Rastatter, Jeffrey C; Rigsby, Cynthia K

    2016-06-01

    The term vascular ring refers to congenital vascular anomalies of the aortic arch system that compress the esophagus and trachea, causing symptoms related to those two structures. The most common vascular rings are double aortic arch and right aortic arch with left ligamentum. Pulmonary artery sling is rare and these patients need to be carefully evaluated for frequently associated tracheal stenosis. Another cause of tracheal compression occurring only in infants is the innominate artery compression syndrome. In the current era, the diagnosis of a vascular ring is best established by CT imaging that can accurately delineate the anatomy of the vascular ring and associated tracheal pathology. For patients with a right aortic arch there recently has been an increased recognition of a structure called a Kommerell diverticulum which may require resection and transfer of the left subclavian artery to the left carotid artery. A very rare vascular ring is the circumflex aorta that is now treated with the aortic uncrossing operation. Patients with vascular rings should all have an echocardiogram because of the incidence of associated congenital heart disease. We also recommend bronchoscopy to assess for additional tracheal pathology and provide an assessment of the degree of tracheomalacia and bronchomalacia. The outcomes of surgical intervention are excellent and most patients have complete resolution of symptoms over a period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

    Science.gov (United States)

    Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

    2015-01-01

    Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

  15. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case–control study

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-01-01

    Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. PMID:25270856

  16. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case-control study.

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-09-29

    We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Urban tertiary care centre and occupational healthcare centre. Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1)≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

  17. Chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B E; Snijder, R J; Mager, J J; van Es, H W; Plokker, H W M; Reesink, H J; Morshuis, W J; Post, M C

    2014-12-01

    Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

  18. Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs

    Directory of Open Access Journals (Sweden)

    Shimodaira Kayoko

    2012-11-01

    Full Text Available Abstract Background Idiopathic pulmonary arterial hypertension (IPAH continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. Methods Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. Results Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. Conclusions Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.

  19. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

    Science.gov (United States)

    Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

    2015-09-01

    Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

  20. Mechanism by which nuclear factor-kappa beta (NF-kB regulates ovine fetal pulmonary vascular smooth muscle cell proliferation

    Directory of Open Access Journals (Sweden)

    Uchenna D. Ogbozor

    2015-09-01

    Full Text Available Platelet activating factor (PAF modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR in pulmonary vascular smooth muscle cells (PVSMC to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a PAF induces NF-kB p65 DNA binding and (b NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

  1. Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension%肾去交感神经对肺动脉高压模型犬肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    张淑娟; 赵庆彦; 蒋学俊; 杨波; 代子玄; 王晓占; 王徐乐; 郭宗文; 于胜波

    2015-01-01

    目的 探讨肾去交感神经(RSD)对肺动脉高压(PAH)模型犬肺血管重构的影响.方法 24只比格犬按随机数字表法随机均分为对照组、PAH组、PAH+ RSD组各8只.检测各组犬实验前血清神经激素水平、心脏超声和血流动力学参数后,对照组右心房注入二甲基甲酰胺(0.1 ml/kg),PAH组右心房注入脱氢野百合碱(2 ml/kg),PAH+ RSD组先行肾去交感神经术,后右心房注入脱氢野百合碱(2 ml/kg).喂养8周,检测各组犬实验后的血清神经激素水平、心脏超声和血流动力学参数后,开胸取肺组织检测肺血管形态学.结果 实验后PAH组、PAH+ RSD组右心室收缩压(RVSP)和肺动脉收缩压(PASP)均显著高于对照组[(42.8±8.7)、(30.8±6.8)比(23.2±5.7) mmHg(1mmHg =0.133 kPa)和(45.1±11.2)、(32.6±7.9)比(24.7 ±7.1)mmHg],且PAH组RVSP和PASP显著高于PAH+ RSD组[均P<0.01].实验后PAH组血清血管紧张素Ⅱ(AngⅡ)和内皮素1水平均显著高于实验前[(228 ±41)比(113±34) pg/ml和(135 ±15)比(77±7)pg/ml,均P<0.01],且肺组织中AngⅡ和内皮素1水平[(65±10)和(96±10)pg/ml]均显著高于对照组[(38±7)和(54±6)pg/ml]和PAH+ RSD组[(46±8)和(67±9)pg/ml](均P<0.01).与对照组相比,PAH组肺泡2型细胞破坏严重,组织纤维化明显,而PAH+ RSD组肺泡2型细胞破坏及组织纤维化较PAH组轻.结论 RSD可降低PAH模型犬肺动脉高压并抑制肺血管重构,此作用可能与其降低神经激素水平有关.%Objective To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH).Methods According to the random number table,24 beagles were randomized into control,PAH and PAH + RSD groups (n =8 each).The levels of neurohormone,echocardiogram and dynamics parameters were measured.Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH + RSD groups) were injected.The PAH + RSD group

  2. Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

    Science.gov (United States)

    Rex, Steffen; Missant, Carlo; Claus, Piet; Buhre, Wolfgang; Wouters, Patrick F

    2008-01-01

    Introduction Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension. Methods In this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 ± 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 μg) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system. Results During pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 ± 0.7 versus 3.7 ± 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 ± 0.3 versus 1.2 ± 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 ± 12 versus 70 ± 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 ± 0.5 versus 3.4 ± 0.8 mWatt·s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 ± 0.33 versus 1.03 ± 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic

  3. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

    Science.gov (United States)

    Galambos, Csaba; Minic, Angela D.; Bush, Douglas; Nguyen, Dominique; Dodson, Blair; Seedorf, Gregory; Abman, Steven H.

    2016-01-01

    Background and Aims Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. Methods Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. Results The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. Conclusions We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and

  4. Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.

    Science.gov (United States)

    Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety.

  5. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Muller H Konrad

    2010-07-01

    Full Text Available Abstract Background Little is known about airway remodelling in bronchial biopsies (BB in smokers and chronic obstructive pulmonary disease (COPD. We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm fragmentation and altered vessel distribution in COPD. Methods To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects. Results Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p Conclusions Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.

  6. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    Science.gov (United States)

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com

  7. Hipertensão arterial pulmonar e acidente vascular encefálico em paciente com Arterite de Takayasu Pulmonary arterial hypertension and cerebrovascular disease in patient with Takayasu Arteritis

    Directory of Open Access Journals (Sweden)

    Carlos Frederico Rodrigues Parchen

    2006-12-01

    Full Text Available Arterite de Takayasu (AT é uma doença rara caracterizada por vasculite dos grandes vasos, principalmente aorta e seus ramos. A inflamação vascular leva a irregularidades na parede do vaso, causando estenoses e aneurismas. O envolvimento da artéria pulmonar (AP é freqüente na AT. Apesar disso, o desenvolvimento de hipertensão arterial pulmonar (HAP é menos comum, alterando o tratamento e o prognóstico dos pacientes. Descrevemos um caso de uma paciente com AT com estenoses múltiplas em artérias pulmonares, HAP e doença cerebrovascular, além de revisão de literatura sobre o assunto.Takayasu arteritis (TA is a rare illness characterized by vasculitis of great vessels, mainly of aorta and its branches. The vascular inflammation leads to irregularities of the vessel wall causing stenosis and aneurysms. The pulmonary artery (PA involvement is frequent in TA. Despite this, the development of pulmonary arterial hypertension is less common, modifying the treatment and the prognosis of the patients. We describe a case of a patient with TA with multiple stenosis in pulmonary arteries, pulmonary arterial hypertension and cerebrovascular disease, as well as review of the literature on the subject.

  8. Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity

    Science.gov (United States)

    Glenny, R. W.; Lamm, W. J.; Bernard, S. L.; An, D.; Chornuk, M.; Pool, S. L.; Wagner, W. W. Jr; Hlastala, M. P.; Robertson, H. T.

    2000-01-01

    To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

  9. VASCULAR EPIPHYTE COMPONENT OCCURING IN URBAN TREES IN THE SQUARE PROFESSOR JOSE INACIO IN PIRATININGA COUNTY, SÃO PAULO STATE

    Directory of Open Access Journals (Sweden)

    Juliano Ricardo Fabricante

    2006-12-01

    Full Text Available Epiphytes are plants cropped in other plants to damage them. The main characteristics of this group of plants is unknown in this part of Brazil, making it important to study this subject. The aim of this work was to characterize the structural and the floristic composition of vascular epiphytes on urban trees; to classify ecological categories species, according to hoist and to calculate community diversity. The studied area (Professor Jose Inacio Square, standed at the municipal district of Piratininga, Sao Paulo State. The climate is Cwa according to Köeppen classification and sandy phase dark red oxisol (latosol. It had been identified 10 species encompassing 6 gender and 6 families, being with best improvement the Bromeliaceae, representing 30 % of data. Tillandsia, with 3 species, was the most abundant gender and featured holoepiphytes were represented, with 70% species. About epiphyte community structure: Tillandsia recurvata and Tillandsia tricholepis were the most important (with bigger VIe in the studies community. Diversity was 2.371 nats/individual to specie and 2.04 nats/individual per family. The small number of species and low diversity index should be due to local conditions, urban area, with different features from that founded at normal eco-systems.

  10. Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

    Science.gov (United States)

    Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

    2010-03-01

    Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

  11. The Role of Anion Exchanger on Pulmonary Vascular Response to Sustained Alveolar Hypoxia in the Isolated Perfused Rabbit Lung

    Directory of Open Access Journals (Sweden)

    Farzaneh Ketabchi

    2015-05-01

    Full Text Available Background: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic pulmonary vasoconstriction (HPV. However, the mechanisms of this physiologic phenomenon are not fully understood. This study was the first to investigate the role of anion exchanger in sustained HPV. Methods: Experiments were performed in the isolated perfused rabbit lung. After preparation, the lungs were divided into six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion exchanger inhibitor-treated [200 µM (n=5 or 400 µM (n=3] hypoxic groups, two HCO3- free hypoxic groups, one control hypoxic group (n=7 and one control normoxic group (n=4. DIDS were added to the perfusate at 10 minutes before starting the experiments. In the HCO3- free groups, HEPES (4-(2-Hydroxyethylpiperazine-1-ethanesulfonic acid were added to the perfusate instead of bicarbonate. Furthermore, in the HEPES1 (n=4 and HEPES2 (n=4 groups, the lungs were ventilated with hypoxic gas with or without CO2, respectively. Results: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the acute (0-20 minutes and sustained (20-60 minutes phases. No alteration in both phases of HPV was detected by DIDS (200 µM. However, DIDS (400 µM, extended the ascending part of acute HPV until min 24. Both phases of HPV were decreased in the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during the rising part of the acute phase of HPV. Conclusions: Since DIDS (400 µM extended acute phase of HPV, and HCO3- free perfusate buffer enhanced rising phase of it, therefore it can be suggested that anion exchanger may modulate HPV especially during the acute phase. The abstract of this article was presented as a poster in the congress of European Respiratory Society (ERS on Monday, 08 September 2014, Munich, Germany and was published in the ERJ September 1, 2014 vol. 44 no. Suppl 58 P2343.

  12. Effect of Nuclear Factor-kappa B on Vascular Endothelial Growth Factor mRNA Expression of Human Pulmonary Artery Smooth Muscle Cells in Hypoxia

    Institute of Scientific and Technical Information of China (English)

    张焕萍; 徐永健; 张珍祥; 许淑云; 倪望; 陈士新

    2004-01-01

    Summary: In order to investigate the effect of nuclear factor-kappa B (NF-κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. The NF-κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBa protein expression was measured by Western blot.RT-PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF-κB p65 nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but the levels of NF-κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups (P<0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h-24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups (P<0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration-dependent manner in hypoxia. In conclusion, NF-κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF-κB activation can decrease the VEGF mRNA expression. h is suggested that the activation of NF-κB is involved in the VEGFmRNA expression of HPASMCs under hypoxia.

  13. Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis.

    Science.gov (United States)

    Fu, Chen; Zhang, Nevin Lianwen; Chen, Bao-Xin; Chen, Zhou Rong; Jin, Xiang Lan; Guo, Rong-Juan; Chen, Zhi-Gang; Zhang, Yun-Ling

    2017-05-01

    To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA). A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules. Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types. A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

  14. Pulmonary Edema: Classification, Mechanisms of Development, Diagnosis

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2009-01-01

    Full Text Available Pulmonary edema remains a topical problem of modern reanimatology. In clinical practice, there is a need for continuous monitoring of the content of extravascular water in the lung and the pulmonary vascular permeability index for the timely detection and treatment of pulmonary edema. This literature review considers the minor mechanisms of pulmonary extravas-cular water exchange in health and in different types of pulmonary edema (acute lung injury, pneumonia, sepsis, postoperative period, burns, injuries etc., as well as the most accessible current (irradiation and dilution studies permitting an estimate of the level of pulmonary extravascular water and the pulmonary vascular permeability index in clinical practice. Key words: pulmonary edema, acute lung injury, pulmonary extravascular water, pulmonary vascular permeability index.

  15. Role of oxidized lipids in pulmonary arterial hypertension

    OpenAIRE

    Sharma, Salil; Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pul...

  16. Avaliação do suprimento sangüíneo vascular pulmonar nos portadores de atresia pulmonar com comunicação interventricular e artérias colaterais sistêmico-pulmonares Assessment of the pulmonary vascular blood supply in patients with pulmonary atresia, ventricular septal defect, and aortopulmonary collateral arteries

    Directory of Open Access Journals (Sweden)

    Ulisses Alexandre Croti

    2005-01-01

    Full Text Available OBJETIVO: Analisar as características morfométricas das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares, avaliando a morfologia do suprimento sangüíneo vascular pulmonar, procurando estabelecer suas implicações no tratamento cirúrgico. MÉTODO: Entre janeiro/1990 e junho/2001, foram estudados 40 pacientes, incluíndo-se os que apresentavam estudo cineangiocardiográfico completo e prévio à primeira intervenção cirúrgica. Analisaram-se as características morfométricas das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares, assim como a distribuição da irrigação sangüínea nos pulmões. Calcularam-se os índices arterial pulmonar (IAAPP, arterial colateral sistêmico-pulmonar (IACSP e arterial neopulmonar total (IANPT = IAAPP + IACSP. O tratamento cirúrgico foi considerado paliativo (TP, paliativo definitivo (TPD e definitivo (TD. RESULTADOS: O TP foi predominante. Não houve diferenças estatisticamente significantes entre os pacientes com TP, TPD e TD, em relação ao IAAPP, IACSP e IANPT. Comparando o IAAPP e o IACSP, não houve diferença entre os índices para o TD (p=0,4309, o IACSP foi maior que o IAAPP para o TP (p=0,0176 e descritivamente também maior para o TPD. O IANPT dos pacientes em TD foi maior que os em TP (p=0,0959. Foram identificados cinco subgrupos morfologicamente semelhantes, denominados: B1, B2, B3, B4 e B5. A mortalidade total foi de 17,5%. CONCLUSÃO: A morfologia do suprimento sangüíneo vascular pulmonar das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares mostrou-se soberana na orientação do tratamento cirúrgico. Independentemente da divisão didática em subgrupos, o TP foi predominante. A mortalidade não apresentou correlação com as características morfométricas.OBJECTIVE: To study the morphometric characteristics of the central pulmonary arteries and aortopulmonary collateral arteries by assessing the morphology

  17. HIPPO-Integrin-linked Kinase Cross-Talk Controls Self-Sustaining Proliferation and Survival in Pulmonary Hypertension

    NARCIS (Netherlands)

    Kudryashova, Tatiana V.; Goncharov, Dmitry A.; Pena, Andressa; Kelly, Neil; Vanderpool, Rebecca; Baust, Jeff; Kobir, Ahasanul; Shufesky, William; Mora, Ana L.; Morelli, Adrian E.; Zhao, Jing; Ihida-Stansbury, Kaori; Chang, Baojun; DeLisser, Horace; Tuder, Rubin M.; Kawut, Steven M.; Sillje, Herman H. W.; Shapiro, Steven; Zhao, Yutong; Goncharova, Elena A.

    2016-01-01

    Rationale: Enhanced proliferation and impaired apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs) are key pathophysiologic components of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Objectives: To determine the role and therapeutic relevance of HIPPO si

  18. Pulmonary manifestations of heartworm disease.

    Science.gov (United States)

    Calvert, C A; Rawlings, C A

    1985-09-01

    The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.

  19. Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

    Directory of Open Access Journals (Sweden)

    Weingartner R.

    1999-01-01

    Full Text Available To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05, systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05 and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05 from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05. Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05 after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05 after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05 after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock

  20. Quantification of tortuosity and fractal dimension of the lung vessels in pulmonary hypertension patients.

    Directory of Open Access Journals (Sweden)

    Michael Helmberger

    Full Text Available Pulmonary hypertension (PH can result in vascular pruning and increased tortuosity of the blood vessels. In this study we examined whether automatic extraction of lung vessels from contrast-enhanced thoracic computed tomography (CT scans and calculation of tortuosity as well as 3D fractal dimension of the segmented lung vessels results in measures associated with PH. In this pilot study, 24 patients (18 with and 6 without PH were examined with thorax CT following their diagnostic or follow-up right-sided heart catheterisation (RHC. Images of the whole thorax were acquired with a 128-slice dual-energy CT scanner. After lung identification, a vessel enhancement filter was used to estimate the lung vessel centerlines. From these, the vascular trees were generated. For each vessel segment the tortuosity was calculated using distance metric. Fractal dimension was computed using 3D box counting. Hemodynamic data from RHC was used for correlation analysis. Distance metric, the readout of vessel tortuosity, correlated with mean pulmonary arterial pressure (Spearman correlation coefficient: ρ = 0.60 and other relevant parameters, like pulmonary vascular resistance (ρ = 0.59, arterio-venous difference in oxygen (ρ = 0.54, arterial (ρ = -0.54 and venous oxygen saturation (ρ = -0.68. Moreover, distance metric increased with increase of WHO functional class. In contrast, 3D fractal dimension was only significantly correlated with arterial oxygen saturation (ρ = 0.47. Automatic detection of the lung vascular tree can provide clinically relevant measures of blood vessel morphology. Non-invasive quantification of pulmonary vessel tortuosity may provide a tool to evaluate the severity of pulmonary hypertension.ClinicalTrials.gov NCT01607489.

  1. Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension.

    Science.gov (United States)

    Bryant, Andrew J; Carrick, Ryan P; McConaha, Melinda E; Jones, Brittany R; Shay, Sheila D; Moore, Christy S; Blackwell, Thomas R; Gladson, Santhi; Penner, Niki L; Burman, Ankita; Tanjore, Harikrishna; Hemnes, Anna R; Karwandyar, Ayub K; Polosukhin, Vasiliy V; Talati, Megha A; Dong, Hui-Jia; Gleaves, Linda A; Carrier, Erica J; Gaskill, Christa; Scott, Edward W; Majka, Susan M; Fessel, Joshua P; Haase, Volker H; West, James D; Blackwell, Timothy S; Lawson, William E

    2016-02-01

    Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.

  2. Duplicated left pulmonary artery: an unknown disease? Three case reports and review of the literature.

    Science.gov (United States)

    Giudici, Valentina; Kanani, Mazyar; Muthialu, Nagarajan; Carr, Michelle; Calder, Alistair D; Owens, Catherine M; Cook, Andrew C; Marek, Jan

    2016-02-01

    We report three cases of an abnormal finding of duplicated left pulmonary artery: two of these occurring in children with Kabuki syndrome and configuring the setting of a pseudo-pulmonary sling without any clinical or cardiac cross-sectional evidence of tracheal compression. The other case instead represents duplicated left pulmonary artery with pulmonary sling caused by the retro-tracheal course of the lower left pulmonary artery associated with "Christmas Tree" arrangement of the tracheo-bronchial system. In both patients with pseudo-pulmonary sling and Kabuki syndrome, the abnormal finding was incidental during echocardiographic examination and neither of the patients required surgical repair for the condition. To the best of our knowledge, they represent the third and fourth cases in which such an anomaly of the pulmonary artery branches not forming a sling is seen in association with Kabuki syndrome. Another case represents our second experience and the second case reported in literature with duplicated left pulmonary artery in the setting of a complex tracheal anatomy. In this symptomatic patient, surgical repair of atrial septal defect and relief of the vascular ring were indicated, and the surgical repair was performed successfully at the age of 3 years.

  3. 应用Swan-Ganz导管测定肺动脉高压犬模型肺循环阻力及心输出量的实验研究%Application of Swan-Ganz catheter to measure pulmonary vascular resistance and cardiac output of canine model with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    林约瑟; 李淑娟; 李轩狄; 李运泉; 王慧深

    2015-01-01

    ObjectiveTo explore the value of Swan-Ganz catheter to measure pulmonary vascular resistance (PVR) and cardiac output (CO) of canine model with pulmonary arterial hypertension (PAH).MethodsSixteen Beagle dogs were randomly divided into two groups, the control group(n=8) and the pulmonary arterial hypertension group (n=8). Arterial blood was obtained to test arterial oxygen saturation. A Swan-Ganz catheter was advanced through the the right jugular vein way to the pulmonary artery and the pulmonary arterial pressure (PAP) were measured. Blood was obtained to test the pulmonary arterial oxygen saturation and plasma concentration of brain natriuretic peptide (BNP). Cardiac output and pulmonary vascular resistance were then calculated according to formula. The pulmonary arterial hypertension group were injected dehydromonocrataline 2.5 mg/kgto set up pulmonary arterial hypertension model. Hemodynamic measure was repeated after eight weeks.ResultsEight weeks after injection of dehydromonocrotaline, the pulmonary arterial systolic pressure, mean pulmonary arterial pressure of the pulmonary arterial hypertension group were significantly increased from (20.33±1.86) mmHg to (50.10±3.72) mmHg, (10.42±1.48) mmHg to (34.30±2.35) mmHg, the pulmonary arterial resistance, pulmonary vascular resistance were significantly increased from (1.10±0.24) Wood to (12.60±0.29) Wood, (2.34±0.33) Wood to (15.68±0.68) Wood, respectively, cardiac output was significantly decreased from (4.60±0.64) L/min to (2.30±0.35) L/min (P<0.05).ConclusionIt is an accurate, stable and repeatable method to apply Swan-Ganz catheter for measuring pulmonary vascular resistance and cardiac output in Beagle models with pulmonary arterial hypertension.%目的:探讨Swan-Ganz导管在肺动脉高压犬模型肺循环阻力及心输出量测定中的应用价值。方法16只比格犬随机分为2组,正常对照组(n=8)、肺动脉高压组(n=8)。穿刺动脉取血检测血氧饱和度。

  4. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  5. Reversal of experimental pulmonary hypertension by PDGF inhibition

    OpenAIRE

    Schermuly, Ralph Theo; Dony, Eva; Ghofrani, Hossein Ardeschir; Pullamsetti, Soni; Savai, Rajkumar; Roth, Markus; Sydykov, Akylbek; Lai, Ying Ju; Weissmann, Norbert; Seeger, Werner; Grimminger, Friedrich

    2005-01-01

    Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the d...

  6. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  7. Ultrasound -- Vascular

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate the ... are the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces ...

  8. Treatment of Hantavirus Pulmonary Syndrome

    Science.gov (United States)

    2007-10-14

    Clinical syndrome Hantaviruses cause a spectrum of vascular-leak syndromes n humans ranging from proteinuria to pulmonary edema and rank hemorrhage...of fatal illness. The illness is haracterized by fever and vascular leakage resulting in noncar- iogenic pulmonary edema followed in severe cases by...cardiopulmonary syndrome (HCPS) o emphasize the important role of cardiogenic shock; among ospitalized patients, death almost invariably results from

  9. Update in pulmonary arterial hypertension.

    Science.gov (United States)

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.

  10. TRICKS Magnetic Resonance Angiography at 3-Tesla for Assessing Whole Lower Extremity Vascular Tree in Patients with High-Grade Critical Limb Ischemia: DSA and TASC II Guidelines Correlations

    Directory of Open Access Journals (Sweden)

    Sheung-Fat Ko

    2012-01-01

    Full Text Available The entire vascular tree of 58 lower extremities with high-grade critical limb ischemia (CLI was assessed with three-station time resolved imaging of contrast kinetics (TRICKS magnetic resonance angiography (T-MRA and correlated with digital subtraction angiography (DSA examinations and Trans-Atlantic Inter-Society Consensus II (TASC II guidelines. Kappa (κ statistics were utilized to evaluate the agreement of stenosis scores (5-point scale; 0 normal to 4 occlusion based on T-MRA and DSA. With DSA as the standard, significant stenosis instances (stenosis score ≥2 among vascular segments were compared. The κ-statistics of image quality (4-point scale; 1 nondiagnostic to 4 excellent of T-MRA and TASC II classification assessed by a radiologist and a vascular surgeon were also evaluated. Among 870 vascular segments, excellent agreement was observed between T-MRA and DSA (mean κ = 0.883 in revealing stenosis (mean stenosis score, 2.1  ±  1.3 versus 2.0  ±  1.3. T-MRA harbored overall high sensitivity (99.5%, specificity (93.6%, positive predictive value (95.4%, negative predictive value (99.6%, and accuracy (97.7% in depicting significant stenosis. Excellent interobserver agreement (mean κ = 0.818 of superb image quality (mean score = 3.5–3.6 of T-MRA and outstanding agreement of TASC II classification of aortoiliac and femoral-popliteal lesions (κ = 0.912–0.917 between two raters further verified the clinical feasibility of T-MRA for treatment planning.

  11. Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH)

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Ley-Zaporozhan, Julia [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Johannes Gutenberg University, Department of Diagnostic and Interventional Radiology; Universitaetsmedizin, Mainz (Germany); Pitton, Michael B.; Schneider, Jens; Wirth, Gesine M.; Dueber, Christoph; Kreitner, Karl-Friedrich [Johannes Gutenberg University, Department of Diagnostic and Interventional Radiology; Universitaetsmedizin, Mainz (Germany); Mayer, Eckhard [Kerckhoff-Hospital Bad Nauheim, Department of Thoracic Surgery, Bad Nauheim (Germany)

    2012-03-15

    To determine the most comprehensive imaging technique for the assessment of pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension (CTEPH). 24 patients with CTEPH were examined by ECG-gated multi-detector CT angiography (MD-CTA), contrast-enhanced MR angiography (ce-MRA) and selective digital subtraction angiography (DSA) within 3 days. Two readers in consensus separately evaluated each imaging technique (48 main, 144 lobar and 449 segmental arteries) for typical changes like complete obstructions, vessel cut-offs, intimal irregularities, incorporated thrombus formations, and bands and webs. A joint interpretation of all three techniques served as a reference standard. Based on image quality, there was no non-diagnostic examination by either imaging technique. DSA did not sufficiently display 1 main, 3 lobar and 4 segmental arteries. The pulmonary trunk was not assessable by DSA. One patient showed thrombotic material at this level only by MD-CTA and MRA. Sensitivity and specificity of MD-CTA regarding CTEPH-related changes at the main/lobar and at the segmental levels were 100%/100% and 100%/99%, of ce-MRA 83.1%/98.6% and 87.7%/98.1%, and of DSA 65.7%/100% and 75.8%/100%, respectively. ECG-gated MD-CTA proved the most adequate technique for assessment of the pulmonary arteries in the diagnostic work-up of CTEPH patients. (orig.)

  12. Tree-space statistics and approximations for large-scale analysis of anatomical trees

    DEFF Research Database (Denmark)

    Feragen, Aasa; Petersen, Jens; Winkler Wille, Mathilde Marie;

    2013-01-01

    parametrize the relevant parts of tree-space well. Using the developed approximate statistics, we illustrate how the structure and geometry of airway trees vary across a population and show that airway trees with Chronic Obstructive Pulmonary Disease come from a different distribution in tree-space than...

  13. Effect of Adrenomedullin on Pulmonary Vascular Structural Remodeling Induced by High Pulmonary Blood Flow in Rats%肾上腺髓质素对大鼠高肺血流性肺血管结构重构的干预作用

    Institute of Scientific and Technical Information of China (English)

    高扬; 齐建光; 李晓惠; 庞璐璐; 金红芳; 杜军保

    2012-01-01

    Objective To explore the effect of adrenomedullin ( ADM) on the pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by high pulmonary blood flow. Methods Twenty - one male 6 - week - old SD rats were randomly divided into control group (n = 7 ) , shunt group ( n = 7 ) and shunt with ADM group (n = 7). Aortocaval shunting was produced in rats of shunt group and shunt with ADM group. In control group,the inferior vena cava and abdominal aorta were only exposed,but shunting procedure was not performed. After 8 weeks,ADM (1. 5 μg · kg-1 · h-1) was subcutaneously administered into rats of shunt with ADM group by mini - osmotic pump for 2 weeks. Pulmonary artery pressures of each rat were evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass.[ RV/( LV + SP) ] was calculated after weighting. The pulmonary artery micro - and ultra - morphologic changes of rats were observed. Results Compared with the rats of control group,pulmonary artery systolic pressure,pulmonary artery diastolic pressure,pulmonary artery mean pressure and RV/( LV + SP) in rats of shunt group were significantly increased (Pa <0.01) ,the muscularization of small pulmonary vessels, relative medial thickness and relative medial area of the pulmonary arteries were also significantly increased (Pa <0. 01 ). Ultrastructural changes, including swelling of endothelial cells, irregularity of inner elastic lamina, and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells,were found in pulmonary arteries of shunting rats. Pulmonary artery pressure and RV/(LV +SP) in rats of shunt with ADM group were significantly decreased compared with those of shunt group (Pa <0.01) ,with the alleviation of pulmonary artery micro - and ultra - morphologic changes. Conclusions ADM subcutaneously administered by mimi - osmotic pump alleviated the development of pulmonary hypertension and

  14. Pulmonary edema

    Science.gov (United States)

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  15. A case of left main pulmonary artery aneurysm associated with valvular pulmonary stenosis in a child.

    Science.gov (United States)

    Lee, Ran; Son, Jae Sung; Park, Yong Mean

    2011-10-01

    Aneurysm of the main pulmonary artery is a rare clinical entity that can be congenital or acquired. Most cases occur in association with other congenital malformations, severe pulmonary hypertension, vasculitides, infectious agents, or collagen vascular disorders. We report here a pediatric case of left pulmonary artery aneurysm associated with valvular pulmonary stenosis and a hypoplastic right pulmonary artery, which we confirmed via multidetector computed tomography angiography.

  16. 重叠综合征患者肺动脉压力与血管内皮功能的研究%Pulmonary arterial pressure and vascular endothelial function in patients with overlap syndrome

    Institute of Scientific and Technical Information of China (English)

    陈文晖; 郝晴虹; 张海

    2012-01-01

    目的:探讨重叠综合征(OS)患者肺功能、睡眠呼吸参数和肺动脉压力的变化以及肺动脉压力与血管内皮功能的相关性.方法:收集2009年2月至2012年1月我院呼吸科诊断的慢性阻塞性肺疾病(COPD)、阻塞性睡眠呼吸暂停低通气综合征(OSAHS)和OS患者各60例,分别测定患者肺功能、睡眠呼吸参数、平均肺动脉压力(mPAP)、血清内皮素1(ET-1)、一氧化氮(NO)和血管内皮生长因子(VEGF)水平.结果:OS组与单纯COPD组和OSAHS组相比,第1秒用力呼气容积(FEV1)(%预测值)、FEV1/用力肺活量(FVC)和快速眼动相睡眠(REM)占总睡眠时间百分比(%)均明显降低(P<0.05);而睡眠呼吸暂停低通气指数(AHI、Epworth嗜睡量表(ESS)评分和mPAP明显增高(P<0.05); OS患者血清中ET-1和VEGF浓度明显高于单纯COPD和单纯OSAHS患者(P<0.05),并与其mPAP呈正相关,而NO浓度显著降低,与mPAP呈负相关.结论:OS患者较单纯的COPD和OSAHS患者更易合并肺动脉高压,外周血ET-1、VEGF和NO的浓度与肺动脉压力有一定的相关性.%Objective To explore the changes of pulmonary function and sleep respiratory parameters, and to analyze the correlation between mean pulmonary arterial pressure (mPAP) and vascular endothelial function in patients with overlap syndrome (OS). Methods Sixty OS patients, 60 chronic obstructive pulmonary disease (COPD) patients and 60 obstructive sleep apnea and hyperpnoea syndrome (OSAHS) patients from Feb 2009 to Jan 2012 were enrolled in this study. Pulmonary function, sleep respiratory parameter, mPAP, endothelin-1 (ET-1), nitric oxide (NO) and vascular endothelial growth factor (VECF) were assessed and analyzed. Results Forced expiaratory volume in 1 s (FEV,)(% predicted value), FEW forced vital capacity (FVC) and rapid eye movement sleep (REM) % were significantly lower in OS patients than those in COPD and OSAHS patients(P<0.05) .while apnea hypopnea index (AM), Epworth sleepiness scale

  17. Assessment of perfusion pattern and extent of perfusion defect on dual-energy CT angiography: Correlation between the causes of pulmonary hypertension and vascular parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young [Dept. of Radiology, Chonbuk National University Medical School and Hospital, Research Institute of Clinical Medicine, Jeonju (Korea, Republic of); Seo, Joon Beom; Oh, Sang Young; Lee, Choong Wook; Lee, Sang Min [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Hwang, Hye Jeon [Dept. of Radiology, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of); Lee, Young Kyung [Dept. of Radiology, Seoul Medical Center, Seoul (Korea, Republic of)

    2014-04-15

    To assess perfusion patterns on a dual-energy pulmonary CT angiography (DECTA) of pulmonary hypertension (PHT) with variable causes and to assess whether the extent of perfusion defect can be used in the severity assessment of PHT. Between March 2007 and February 2011, DECTA scans of 62 consecutive patients (24 men, 38 women; mean age, 58.5 ± 17.3 [standard deviation] years; range, 19-87 years) with PHT were retrospectively included with following inclusion criteria; 1) absence of acute pulmonary thromboembolism, 2) maximal velocity of tricuspid regurgitation jet (TR Vmax) above 3 m/s on echocardiography performed within one week of the DECTA study. Perfusion patterns of iodine map were divided into normal (NL), diffuse heterogeneously decreased (DH), multifocal geographic and multiple peripheral wedging patterns. The extent of perfusion defects (PD), the diameter of main pulmonary artery (MPA) and the ratio of ascending aorta diameter/MPA (aortopulmonary ratio, APR) were measured. Pearson correlation analysis was performed between TR Vmax on echocardiography and CT imaging parameters. Common perfusion patterns of primary PHT were DH (n = 15) and NL (n = 12). The perfusion patterns of secondary PHT were variable. On the correlation analysis, in primary PHT, TR Vmax significantly correlated with PD, MPA and APR (r = 0.52, r = 0.40, r = -0.50, respectively, all p < 0.05). In secondary PHT, TR Vmax significantly correlated with PD and MPA (r = 0.38, r = 0.53, respectively, all p < 0.05). Different perfusion patterns are observed on DECTA of PHT according to the causes. PD and MPA are significantly correlated with the TR Vmax.

  18. Differential Sensitivities of Pulmonary and Coronary Arteries to Hemoglobin-Based Oxygen Carriers and Nitrovasodilators: Study in a Bovine Ex Vivo Model of Vascular Strips

    Science.gov (United States)

    2010-01-01

    lsev ier.c omflocate/ vph Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators...preparation has been used extensively in multiple studies that led to the discovery of NO as endothelium-derived relaxing factor (lgnarro et al., 1984...G.M .• Wood, K.S., Chaudhuri, G., 1988a. Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use or pyrogallol and

  19. A method for quantitative characterization of growth in the 3-D structure of rat pulmonary arteries.

    Science.gov (United States)

    Razavi, Hedi; Dusch, Marie N; Zarafshar, Shahrzad Y; Taylor, Charles A; Feinstein, Jeffrey A

    2012-03-01

    Understanding mechanisms causing pulmonary vascular disease (PVD) frequently requires a thorough understanding of the underlying structural changes in the pulmonary circulation. Animal models have been used extensively to study different forms of PVD but conventional experimental techniques are limited in their ability to allow the study of the whole pulmonary vasculature at once. In this study, we introduce novel techniques of arterial casting, high-resolution imaging and tree analysis to study the pulmonary circulation in rodent models. Male Sprague-Dawley rats were used at 20, 36, 52, 100 and 160 days of age. A technique involving arterial casting with Microfil silicone polymer, high-resolution micro-computed tomography (micro-CT) at 12.5 μm resolution and image data analysis involving segmentation and skeletonization was developed to both qualitatively and quantitatively describe the changes in the pulmonary vasculature with increasing age. Parameters identified to affect the quality of pulmonary arterial casting included polymer flow rate, total injected volume, polymer viscosity and polymerization time. By optimizing these parameters, we successfully created arterial casts of the pulmonary circulation in rats of different ages and demonstrated the feasibility of quantitatively characterizing the changes in the number of vessels with postnatal growth. These preliminary data suggest that the number of vessels with lumen diameters of 50-200 μm increases rapidly in both lungs between 52 and 100 days of age. With this new technique, the pulmonary vasculature can now be studied in a whole lung animal model to better understand the global effects of disease on vascular structure.

  20. The pulmonary vascular blood supply in the pulmonary atresia with ventricular septal defect and its implications in surgical treatment O suprimento sangüíneo vascular pulmonar na atresia pulmonar com comunicação interventricular e suas implicações no tratamento cirúrgico

    Directory of Open Access Journals (Sweden)

    Ulisses Alexandre Croti

    2003-10-01

    Full Text Available OBJECTIVE: With base in the studies cineangiocardiography of pacients with pulmonary atresia (PA with ventricular septal defect (VSD, to identify in the groups proposed by BARBERO MARCIAL, subgroups with similar morphological characteristics, to measure their central pulmonary arteries (CPA and major aortopulmonary collateral arteries (MAPCA, thereby establishing their implications in surgical treatment. METHOD: Sixty three patients were classified in groups A (15, B (40 and C (8 between january 1990 and june 2001. Patients with complete cineangiocardiograms prior to the first surgical intervention were included in this study, being calculated the pulmonary arterial index (PAI, the major aortopulmonary collateral arterial index (MAPCAI and the total neopulmonary arterial index (TNPAI = PAI + MAPCAI. Surgical treatment was considered palliative (PT, definitively palliative (DPT and definitive (DT. RESULTS: Nine subgroups were identified, A (A1 and A2, B (B1, B2, B3, B4 and B5 and C (C1 and C2. In group A, the PAI of patients for DT was higher than for PT patients (p=0,0092. In group B, the TNPAI of DT patients was greater than for PT patients (p=0,0959. In group C, the MAPCAI in DPT patients was lower than in PT and DT patients. In the group A was not mortality, in the group B was of 17,5% and in the group C was of 12,5%. CONCLUSIONS:Among the groups A, B e C was possible to identifiy nine subgroups, the morphologic and morphometric characteristics allowed to suggest the surgical treatment in the patients of the group A had larger chance of TD, the group B of TP and the group C of TPD. The mortality presented larger correlation with the morphologic characteristics that with the morphometric.OBJETIVO: Com base nos estudos cineangiocardiográficos de pacientes portadores de atresia pulmonar (AP com comunicação interventricular (CIV, identificar nos grupos propostos pela classificação de BARBERO MARCIAL, subgrupos com suprimento sang

  1. Vascular Cures

    Science.gov (United States)

    ... is Possible EVERY DOLLAR SAVES LIVES. Donate Now Vascular Cures innovates patient-centered research, catalyzes breakthrough collaborations and empowers people in their vascular health journey. what is vascular disease PATIENTS see ...

  2. Vascular ring

    Science.gov (United States)

    ... subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... Vascular ring is rare. It accounts for less than 1% of all congenital heart problems. The condition ...

  3. Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    López Gude, María Jesús; Pérez de la Sota, Enrique; Pérez Vela, Jose Luís; Centeno Rodríguez, Jorge; Muñoz Guijosa, Christian; Velázquez, María Teresa; Alonso Chaterina, Sergio; Hernández González, Ignacio; Escribano Subías, Pilar; Cortina Romero, José María

    2017-07-07

    Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm(-5), and group 2, which included the remaining 120 patients. Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. The expression and significance of PPARγand MMP-9 in pulmonary vascular endothelial cells with chronic obstructive pulmonary disease%PPARγ和MMP-9在慢性阻塞性肺疾病肺血管内皮细胞的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李海燕; 成炜; 丛金鹏; 于文成

    2013-01-01

    Objective In order to investigate the effect of peroxisome proliferators activated receptor gamma and matrix metalloproteinase-9 in pulmonary vascular inflammation and remodeling in patients with chronic obstructive pulmonary disease(COPD) by detecting the expression of PPARγand MMP-9 of pulmonary vascular endothelial cells. Methods Lung specimens were collected from the male patients who with lung carcinoma and smoking history and need to be operated in thoracic surgery, 30 patients were divided into 2 groups, control group:patients with normal pulmonary function (non-COPD group) and patients with COPD(COPD group), each of 15 cases, matched with age. Air flow obstruction was determined by pulmonary function test and pulmonary artery pressure were examined by continuous wave Doppler echocardiographic measurement of the tricuspid regurgitant jet, and the smoking index were recorded in all patients before the operations. The remodeling of pulmonary artery remodeling was observed with HE staining under microscope and triple strains, lumen area, arteries walls, intimal area, muscular arteries, partial muscular arteries, non partial muscular arteries were measured, the expression of PPARγ and MMP-9 of pulmonary vascular endothelial cells were measured by means of immunohisto-chemistry, analysis were made. Results (1)Compared with control group, arteries walls of COPD group congested and swelled, inflammation cells increased, the thickness of intimal layer, walls of intra-acinar pulmonary muscular arteries was significantly higher, the area of its lumen was narrow and the proportion of their muscular arteries was higher, the area of collagen fibrils was increased. (2)The expression of PPARγin control group was higher than that in COPD group (P<0.01), and the expression of MMP-9 in COPD group was higher than that in control group. (3)Correlation analysis:An negative correlations were showed with the expression of PPARγand MMP-9(r=-0.85, P<0.01). The expression of

  5. Effects of pravastatin on pulmonary arteries and aorta reactivity in monocrotalin-induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    PGUERARD; 0BARTHEZ; FGOIRAND; LROCHETTE; MBARDOU; MDUMAS

    2004-01-01

    AIM: Vascular injury caused by monocrotalin (MC) can affect endothelial regulation and induces pulmonary hypertension and heart failure. We showed previously that pravastatin prevented the development of MC-induced pulmonary hypertension by improving pulmonary arteries (PA) endothelium dependent vasodilation. The aims of this study were to compare the protective

  6. Extensive pulmonary sarcoid reaction in a patient with BMPR-2 associated idiopathic pulmonary arterial hypertension

    NARCIS (Netherlands)

    Braam, Evelien A J E; Quanjel, Marian J R; Van Haren-Willems, Jolanda H G M; Van Oosterhout, Matthijs F M; Vink, Aryan; Heijdra, Yvonne F; Kwakkel-van Erp, Johanna M

    2016-01-01

    Pulmonary arterial hypertension is a progressive life-threatening disease characterized by vascular remodeling. There is evidence that varied immune mechanism play an important role in progression of pulmonary hypertension. We describe a case of a 35-year-old woman with idiopathic pulmonary arterial

  7. The role of increased pulmonary blood flow in pulmonary arterial hypertension

    NARCIS (Netherlands)

    van Albada, ME; Schoemaker, RG; Kemna, MS; Cromme - Dijkhuis, A; van Veghel, R; Berger, RMF

    2005-01-01

    Chronic increased pulmonary blood flow is considered a pre-requisite for the induction of advanced vascular lesions in pulmonary arterial hypertension in congenital heart defects. The aim of the present study was to characterise the effects of increased pulmonary flow induced by an aortocaval shunt

  8. [Pathophysiology and classification of pulmonary hypertension].

    Science.gov (United States)

    Sládková, H; Jansa, P; Susa, Z; Aschermann, M

    2004-09-01

    Pulmonary hypertension is present when the mean pulmonary pressure is increased above 25 mm Hg in a rest or above 30 mm Hg during exercise. It is possible to divide it from different point of view. Well known is pathophysiologic classification and Venice classification suggested by WHO symposium 2003. The rise of arterial pulmonary pressure is caused by three essential abnormalities, these are elevated pulmonary vascular resistance, blood flow and pulmonary artery wedge pressure. Vasoconstriction, remodeling of vessels and in situ trombosis are pathogenetic mechanism which contribute to rise of pulmonary hypertension.

  9. Varicosity of the pulmonary veins

    Energy Technology Data Exchange (ETDEWEB)

    Leicher-Dueber, A.; Lindner, P.; Schild, H.; Plewe, G.

    1986-04-01

    Varicosity of the pulmonary veins is a rare anomaly of the pulmonary vascular system. The varices do not usually change in size over years, do not cause symptoms and need no therapy. However, raised left atrial pressure can cause increase in the diameter of pulmonary vein varices. A case of lung vein varicosity in the right middle and upper lobe associated with coarctation of the aorta and an anomalous upper-middle lobe vein was observed over a period of 10 years. Increase in left atrial pressure (aortic and relative mitral regurgitation) led to enlargement of the pulmonary veins.

  10. Fator von Willebrand e disfunção endotelial pulmonar. Implicações prognósticas von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

    Directory of Open Access Journals (Sweden)

    Antonio Augusto B. Lopes

    1998-03-01

    Full Text Available OBJETIVO: Avaliar alterações quantitativas e estruturais do fator von Willebrand (fvW circulante em 40 pacientes com hipertensão pulmonar pré-capilar e verificar possíveis implicações prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS: A atividade antigênica plasmática do fator von Willebrand (vWF:Ag foi analisada por imunoeletroforese. A concentração de multímeros de baixo peso molecular em relação ao total de multímeros do fvW (MBPM% e o grau de fragmentação de sua subunidade principal foram analisados por Western immunoblotting. RESULTADOS: Em 40 pacientes, observamos aumento significativo de vWF:Ag em relação aos controles (pPURPOSE: To analyze quantitative and structural changes in circulating von Willebrand factor (vWF in 40 precapillary pulmonary hypertensive patients, as an attempt to identify possible correlations between endothelial cell dysfunction and patient short-term (one year survival. METHODS: Plasma antigenic activity of vWF (vWF:Ag was analyzed by immunoelectrophoresis. The relative concentration of vWF low molecular weight multimers (LMWM% and the composition of vWF subunit were determined by densitometric analysis of Western blots. RESULTS: vWF:Ag was importantly increased in patients in comparison with normals (p<0.001. Patients also had increased LMWM% (p<0.001 and increased degradation of vWF main subunit (p<0.05. At the beginning of the study, nonsurvivors (N=11 had higher vWF:Ag (p<0.001 and LMWM% (p<0.005 values in comparison with survivors. LMWM% was selected by logistic regression analysis as a predictor of death during the first year of follow-up (p<0.05. CONCLUSION: Marked changes in circulating vWF likely reflect extensive pulmonary vascular endothelial cell dysfunction and are associated with poor short-term prognosis in pulmonary hypertension.

  11. 先心病肺高压与血管内皮受损%Pulmonary Hypertension Secondary to Congenital Heart Diseases and Vascular Endot helial Damage

    Institute of Scientific and Technical Information of China (English)

    周文斌; 陈绍军

    2001-01-01

    @@  1 血管内皮细胞(Vascular endothelial cell VEC)的结构与功能 血管内皮细胞是位于循环的血液与血管壁内皮下组织之间的单层细胞,血管内细胞的管腔面上有突起的微绒毛。血管内皮细胞有一个特殊的细胞器即Weibel-Palade小体,目前仅发现血管内皮细胞有此小体,故被视为血管内皮细胞特异形态学标志,而此小体是vWF(von Willebrand Fator血管性血友病因子)贮存和加工的部位。

  12. VESGEN Software for Mapping and Quantification of Vascular Regulators

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

    2012-01-01

    VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

  13. Acute pulmonary vasodilatory properties of amlodipine in humans with pulmonary hypertension.

    OpenAIRE

    Woodmansey, P. A.; O'Toole, L.; Channer, K S; Morice, A H

    1996-01-01

    OBJECTIVE: Calcium antagonists are the only oral vasodilators shown to influence mortality in primary pulmonary hypertension, but the high doses required are often poorly tolerated. Amlodipine is a novel, relatively well tolerated, calcium antagonist. It has not been previously tested in humans with pulmonary hypertension. DESIGN: Calcium antagonists are claimed to be of benefit in the 20-30% of patients who respond--that is, whose mean pulmonary artery pressure and pulmonary vascular resista...

  14. Pulmonary embolus

    Science.gov (United States)

    ... Blood clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... area). This type of clot is called a deep vein thrombosis (DVT) . The blood clot breaks off and travels ...

  15. Clasificación funcional de la hipertensión pulmonar en niños: informe del task force pediátrico del Pulmonary Vascular Research Institute (PVRI, Panamá 2011 Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011

    Directory of Open Access Journals (Sweden)

    Astrid E Lammers

    2012-12-01

    Full Text Available Los miembros del Task Force pediátrico del Pulmonary Vascular Research Institute (PVRI, su sigla en Inglés fueron conscientes de la necesidad de desarrollar una clasificación funcional de la hipertensión pulmonar en niños. La clasificación que se propone sigue el mismo patrón y utiliza los mismos criterios de la clasificación de la hipertensión pulmonar específica para adultos de Dana Point. Fue necesario incluir modificaciones para los niños, teniendo en cuenta que la edad, el crecimiento físico y la madurez influyen en la expresión funcional de la enfermedad. Es necesario definir el estado clínico del niño, pues ello facilita revisar la evolución del mismo en una forma consistente y objetiva a medida que él/ella crecen. Particularmente en los niños más jóvenes, se trató de incluir indicadores objetivos como el crecimiento, la necesidad de alimentos suplementarios y los registros de asistencia al colegio y a la guardería. Esto ayuda a monitorear la evolución clínica y la respuesta al tratamiento a través de los años y facilita el desarrollo de algoritmos de tratamiento en estos pacientes. Se presenta un artículo de consenso sobre una clasificación aplicable a los niños con hipertensión pulmonar que se discutió en la reunión anual del PVRI que se llevó a cabo en Panamá en febrero de 2011.The members of the Pediatric Task Force of the Pulmonary Vascular Research Institute (PVRI were aware of the need to develop a functional classification of pulmonary hypertension in children. The proposed classification follows the same pattern and uses the same criteria as the Dana Point pulmonary hypertension specific classification for adults. Modifications were necessary for children, since age, physical growth and maturation influences the way in which the functional effects of a disease are expressed. It is essential to encapsulate a child's clinical status, to make it possible to review progress with time as he/she grows

  16. Related risk factors for pulmonary infections in cerebral vascular disease patients%脑血管疾病患者合并肺部感染的相关危险因素调查

    Institute of Scientific and Technical Information of China (English)

    黄贞

    2013-01-01

    OBJECTIVE To explore the related risk factors for the pulmonary infections in the patients with cerebral vascular diseases so as to perform the targeted prevention. METHODS The medical records of 176 cases with cerebral vascular diseases were retrospectively analyzed, the related risk factors for the combined pulmonary infections were analyzed as well. RESULTS There were 36 cases with pulmonary infections, and the incidence rate was 20. 46%. The incidence rates of the pulmonary infections were as follows:the people whose age was less than 70 years 11. 98% , the people whose age was more than 70 years 4. 38% , the male 23. 91 % , the female 16. 67% , the people with disorder of consciousness 51. 72%, the people without consciousness disorder 14. 29%, the hemorrhagic patients 31. 96%, the ischemic patients 6. 33%, the people with invasive operation 37. 50%, the people without the invasive operation 10. 71%, the people complicated with diabetes mellitus 60. 00%, the people without complicated diabetes mellitus 10. 64% , the people combined with chronic bronchitis 76. 92%, the people without chronic bronchitis 10. 67%, the people with intracranial hypertension 55. 56%, the people without intracranial hypertension 16. 46% , the people with the bedridden duration less than 10 days 6. 67% ,and the people with the bedridden duration more than 10 days 25. 19%. The difference in the incidence of pulmonary infections between the patients with different age, consciousness disorders, cerebrovascular disease types, invasive operations, diabetes, chronic bronchitis, intracranial hypertension, and bedridden duration was statistically significant(P< 0. 05). Multivariate logistic analysis revealed that the age, impaired consciousness, cerebrovascular disease types, invasive operation, diabetes, chronic bronchitis, and bedridden time were the independent risk factors(P<0. 01). CONCLUSION The incidence rate of the pulmonary infections is relatively high in the patients with the

  17. Avaliação semiquantitativa ecocardiográfica de dilatações vasculares intrapulmonares em candidatos a transplante hepático: correlação com avaliação de shunt e parâmetros funcionais pulmonares Semiquantitative echocardiographic evaluation of intrapulmonary vascular dilatations: correlation with evaluation of shunt levels and pulmonary function parameters

    Directory of Open Access Journals (Sweden)

    Maria Angélica Pires Ferreira

    2009-02-01

    Full Text Available OBJETIVO: Verificar a relação entre a avaliação semiquantitativa de dilatações vasculares intrapulmonares (DVIP e a avaliação quantitativa de shunt, e descrever achados clínicos e funcionais pulmonares em uma amostra de hepatopatas com DVIP. MÉTODOS: Pacientes com ecocardiografia transtorácica (ETT positiva para DVIP foram submetidos à avaliação clínica e de função pulmonar assim como à quantificação de shunt intrapulmonar (cintilografia com macroagregados de albumina marcados com tecnécio-99m e por gasometria com oxigênio a 100%. RESULTADOS: Foram estudados 28 pacientes cirróticos (média de idade, 47,5 anos; 60,7% dos casos classificados como Child-Pugh B. Uma escala de 4 pontos, em ordem ascendente, foi utilizada para medir a intensidade das DVIP, classificada de 1 a 4, respectivamente, em 13 (46,4%, 9 (32,1%, 2 (7,1% e 4 (14,3% dos pacientes. A amostra foi dividida em grupo baixa intensidade (escores 1 e 2 e grupo alta intensidade (escores 3 e 4. A média de shunt por cintilografia foi 14,9% na amostra total, sendo menor no grupo baixa intensidade (11,7% vs. 26,3%; p = 0,01. O grupo alta intensidade teve maiores valores de shunt através de gasometria (8,3% vs. 16,3%; p OBJECTIVE: To correlate semiquantitative evaluation of intrapulmonary vascular dilatations (IPVD with quantitative evaluation of shunt levels, as well as to describe clinical and pulmonary function findings in a sample of liver disease patients with IPVD. METHODS: Patients presenting transthoracic echocardiography (TTE positivity for IPVD underwent clinical evaluation, pulmonary function tests and pulmonary shunt quantification (scintigraphy with technetium-99m-labeled albumin macroaggregates and blood gas analysis after pure oxygen breathing. RESULTS: A total of 28 liver cirrhosis patients were studied (mean age, 47.5 years; 60.7% were Child-Pugh class B. A 4-point, ascending scale was used as a measure of IPVD intensity, which was scored as 1, 2, 3

  18. 64-MDCT imaging of the coronary arteries and systemic arterial vascular tree in a single examination: optimisation of the scan protocol and contrast-agent administration.

    Science.gov (United States)

    Napoli, A; Anzidei, M; Francone, M; Cavallo Marincola, B; Carbone, I; Geiger, D; Zaccagna, F; Di Paolo, P L; Zini, C; Catalano, C; Passariello, R

    2008-09-01

    The aim of this study was to validate a 64-row multidetector computed tomography (64-MDCT) acquisition protocol with biphasic administration of contrast medium for comprehensive assessment of the coronary and systemic arterial tree in a single examination. The scanning protocol comprised two acquisitions: an electrocardiograph (ECG)-gated scan at the level of the heart, followed by a total-body, low-dose scan of the systemic arterial circulation. Twenty patients were evaluated using two different strategies for contrast administration. In ten patients, the delay between the two acquisitions was set at 40 s, whereas in the remaining patients, it varied between 45 s and 65 s. For both strategies, the degree of systemic arterial opacification and the attenuation gradient between arterial and venous structures were quantitatively assessed at six extracoronary locations. Two observers evaluated in consensus the presence or absence of atherosclerosis and the degree of stenosis of arterial segments. Three hundred coronary segments were analysed. Arterial-wall changes were depicted in 155 (51%) segments, and in 35 (23%), the degree of stenosis was > 50%. Of the 640 extracoronary arterial segments, 250 (39%) presented atherosclerotic wall alterations, in 50 (20%), the degree of stenosis was > 50% and five were affected by aneurysmal dilatation. The magnitude of arterial opacification values and attenuation gradients between arterial and venous structures were significantly higher in patients scanned with the 40-s fixed-delay strategy. Whole-body CT angiography with biphasic administration of contrast agent and fixed scan delay has been shown to be a feasible and reproducible technique. Comprehensive data on the global atherosclerotic burden potentially offer important therapeutic options for subclinical, high-risk segments.

  19. Vascular Diseases

    Science.gov (United States)

    The vascular system is the body's network of blood vessels. It includes the arteries, veins and capillaries that carry ... to and from the heart. Problems of the vascular system are common and can be serious. Arteries ...

  20. Vascular Vertigo

    OpenAIRE

    Mazyar Hashemilar; Masoud Nikanfar; Dariush Savadi Oskoui

    2017-01-01

    Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vert...

  1. Sildenafil in the treatment of pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Christopher F Barnett

    2006-12-01

    Full Text Available Christopher F Barnett1,2, Roberto F Machado1,21Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAAbstract: The therapy of pulmonary hypertension has evolved rapidly in the last 10 years from the use of non-selective vasodilators to drugs that specifically target pulmonary vasodilation, endothelial function, and vascular remodeling. Sildenafil is a phosphodiesterase type 5 inhibitor that has an expanding role in the treatment of pulmonary hypertension. Case series and small studies, as well as the first large randomized controlled trial, have  demonstrated the safety and efficacy of sildenafil in improving mean pulmonary artery pressure, pulmonary vascular resistance, cardiac index, and exercise tolerance in pulmonary arterial hypertension. It may be useful in adults, children, and neonates after cardiac surgery, with left heart failure, in fibrotic pulmonary disease, high altitude exposure, and thromboembolic disease, and in combination with other therapies for pulmonary hypertension, such as inhaled iloprost. The oral formulation and favorable adverse effect profile make sildenafil an attractive alternative in the treatment of selected patients with pulmonary hypertension. Keywords: sildenafil, phosphodiesterase inhibitor, pulmonary hypertension, right heart failure

  2. Heart Failure and Pulmonary Hypertension

    OpenAIRE

    Shin, Jordan T.; Semigran, Marc J.

    2010-01-01

    When PH and RV dysfunction accompany HF, the impact on functional capacity and prognosis are ominous. Newer clinical strategies to preferentially lower pulmonary pressures and pulmonary vascular tone improve functional performance and symptoms of heart failure by targeting the NO signal transduction pathways as with PDE5 inhibition. Additional studies are needed to delineate if these therapies will impact long-term patient outcomes and to elucidate the specific mechanisms whereby these treatm...

  3. A novel multiscale topo-morphometric approach for separating arteries and veins via pulmonary CT imaging

    Science.gov (United States)

    Saha, Punam K.; Gao, Zhiyun; Alford, Sara; Sonka, Milan; Hoffman, Eric

    2009-02-01

    Distinguishing arterial and venous trees in pulmonary multiple-detector X-ray computed tomography (MDCT) images (contrast-enhanced or unenhanced) is a critical first step in the quantification of vascular geometry for purposes of determining, for instance, pulmonary hypertension, using vascular dimensions as a comparator for assessment of airway size, detection of pulmonary emboli and more. Here, a novel method is reported for separating arteries and veins in MDCT pulmonary images. Arteries and veins are modeled as two iso-intensity objects closely entwined with each other at different locations at various scales. The method starts with two sets of seeds -- one for arteries and another for veins. Initialized with seeds, arteries and veins grow iteratively while maintaining their spatial separation and eventually forming two disjoint objects at convergence. The method combines fuzzy distance transform, a morphologic feature, with a topologic connectivity property to iteratively separate finer and finer details starting at a large scale and progressing towards smaller scales. The method has been validated in mathematically generated tubular objects with different levels of fuzziness, scale and noise. Also, it has been successfully applied to clinical CT pulmonary data. The accuracy of the method has been quantitatively evaluated by comparing its results with manual outlining. For arteries, the method has yielded correctness of 81.7% at the cost of 6.7% false positives and 11.6% false negatives. Our method is very promising for automated separation of arteries and veins in MDCT pulmonary images even when there is no mark of intensity variation at conjoining locations.

  4. Study on the pulmonary mean transit time and the pulmonary blood volume by RI-cardiogram

    Energy Technology Data Exchange (ETDEWEB)

    Ushio, N.

    1987-03-01

    The pulmonary mean transit time and the pulmonary blood volume in cases of cardio-pulmonary disease were measured using Giuntini's method which is considered the most appropriate among radiocardiographic methods. The errors in this method were confirmed to be almost negligible. The results obtained were as follows: 1) The pulmonary mean transit time was related to the systemic mean transit time and markedly prolonged in left heart failure. On the other hand, it was markedly shortened in some cases of chronic pulmonary disease, particularly pulmonary emphysema. 2) The pulmonary blood volume tended to increase in left heart disorders and mitral valve disease and tended to decrease in the chronic pulmonary disease. The decrease was conspicuous particularly in some cases of pulmonary emphysema. 3) A structural change of the pulmonary vascular system in the chronic pulmonary disease appeared to bring about shortening of the pulmonary mean transit time and a decrease in the pulmonary blood volume. The pathophysiology of cardio-pulmonary disease can be more clarified by the RI-cardiogram used in this study, in which the pulmonary mean transit time and the pulmonary blood volume are used as the indicator.

  5. Congenital diaphragmatic hernia-associated pulmonary hypertension.

    Science.gov (United States)

    Harting, Matthew T

    2017-06-01

    Congenital diaphragmatic hernia (CDH) is a complex entity wherein a diaphragmatic defect allows intrathoracic herniation of intra-abdominal contents and both pulmonary parenchymal and vascular development are stifled. Pulmonary pathology and pathophysiology, including pulmonary hypoplasia and pulmonary hypertension, are hallmarks of CDH and are associated with disease severity. Pulmonary hypertension (PH) is sustained, supranormal pulmonary arterial pressure, and among patients with CDH (CDH-PH), is driven by hypoplastic pulmonary vasculature, including alterations at the molecular, cellular, and tissue levels, along with pathophysiologic pulmonary vasoreactivity. This review addresses the basic mechanisms, altered anatomy, definition, diagnosis, and management of CDH-PH. Further, emerging therapies targeting CDH-PH and PH are explored. Published by Elsevier Inc.

  6. Pulmonary Thromboendarterectomy for Pulmonary Hypertension Before Considering Transplant

    Science.gov (United States)

    Kooperkamp, Hannah; Mehta, Inder; Fary, David; Bates, Michael

    2017-01-01

    Background: In cases of chronic thromboembolic pulmonary hypertension (CTEPH), referral for possible surgical intervention is important because surgery can be curative. Surgery necessitates cardiopulmonary bypass and deep circulatory arrest with pulmonary thrombectomy and bilateral endarterectomy (PTE). If surgery fails, lung transplant is the next best surgical option. Medical treatment is also an important adjunct. Case Report: A 35-year-old female presented 3 months after a pulmonary embolus was found to be completely occluding her left pulmonary artery. She was found to have pulmonary hypertension with a pulmonary artery pressure of 81/33 mmHg, with a mean pressure of 52 mmHg. The right atrial pressure was also severely elevated at 29 mmHg, and her echocardiogram revealed severe tricuspid regurgitation and severe right ventricular dysfunction. She underwent PTE and postoperatively was followed by the heart failure team. Her 6-minute walk distance improved from 396 meters at 1 month to 670 meters at 7 months, and her pulmonary artery pressure improved significantly to 55/17 mmHg with a mean pressure of 31 mmHg. The patient's right atrial pressure also improved significantly from 29 mmHg to 13 mmHg. Conclusion: CTEPH is likely underrecognized, and patients with pulmonary hypertension or a history of pulmonary embolism should be screened for CTEPH. This case illustrates the surgical treatment for CTEPH and discusses alternative and adjunctive treatments. Residual pulmonary hypertension after PTE occurs in approximately 35% of patients. Overall, 4-year mortality rates after surgery appear to be approximately 15%, and mortality rates correlate with the postoperative pulmonary vascular resistance. Recognition of chronic pulmonary thromboembolic disease as the etiology of pulmonary hypertension warrants evaluation for surgery.

  7. Pulmonary artery haemodynamic properties in patients with pulmonary hypertension secondary to rheumatic mitral stenosis.

    Science.gov (United States)

    Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin

    2012-12-01

    We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.

  8. pulmonary performance in asymptomatic young nigerian population ...

    African Journals Online (AJOL)

    Bioline

    Ascorbic acid was given orally at a dose of 1.50 mg /kg body weight; and salbutamol at a dose of 70 ... vascular resistance in the pulmonary bed. The ... forces supporting and moving the lungs with ... Analysis of static pressure – volume data ... exercise (Aggarwal et al, 2000). ... effects of ascorbic acid on pulmonary function.

  9. Pulmonary langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Suri Harpreet S

    2012-03-01

    Full Text Available Abstract Pulmonary Langerhans Cell Histiocytosis (PLCH is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

  10. Anesthetic Management of Pediatric Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Mediha Turktan

    2015-06-01

    Full Text Available Pulmonary arterial hypertension is the most important cause of morbidity and mortality associated with congenital heart disease. Patients in this group have a greater peroperative cardiovascular risks including cardiac arrest, pulmonary hypertensive crisis and death compared the normal population. The main purpose of anesthesia is to avoid increased pulmonary vascular resistance and myocardial depression. [Archives Medical Review Journal 2015; 24(2.000: 149-158

  11. Iron deficiency in patients with idiopathic pulmonary arterial hypertension

    NARCIS (Netherlands)

    van Empel, Vanessa P M; Lee, Joy; Williams, Trevor J; Kaye, David M

    2014-01-01

    BACKGROUND: Iron deficiency has been reported to be highly prevalent in idiopathic pulmonary arterial hypertension (iPAH) patients, with the potential to influence cardiac performance, pulmonary artery pressures and the pulmonary vascular response to hypoxia. METHODS: Iron status was evaluated in 29

  12. Clasificación funcional de la hipertensión pulmonar en niños: Informe del task force pediátrico del Pulmonary Vascular Research Institute (PVRI, Panamá 2011

    Directory of Open Access Journals (Sweden)

    Astrid E. Lammers

    2012-11-01

    Full Text Available Los miembros del Task Force pediátrico del Pulmonary Vascular Research Institute (PVRI, su sigla en Inglés fueron conscientes de la necesidad de desarrollar una clasificación funcional de la hipertensión pulmonar en niños. La clasificación que se propone sigue el mismo patrón y utiliza los mismos criterios de la clasificación de la hipertensión pulmonar específica para adultos de Dana Point. Fue necesario incluir modificaciones para los niños, teniendo en cuenta que la edad, el crecimiento físico y la madurez influyen en la expresión funcional de la enfermedad. Es necesario definir el estado clínico del niño, pues ello facilita revisar la evolución del mismo en una forma consistente y objetiva a medida que él/ella crecen. Particularmente en los niños más jóvenes, se trató de incluir indicadores objetivos como el crecimiento, la necesidad de alimentos suplementarios y los registros de asistencia al colegio y a la guardería. Esto ayuda a monitorear la evolución clínica y la respuesta al tratamiento a través de los años y facilita el desarrollo de algoritmos de tratamiento en estos pacientes. Se presenta un artículo de consenso sobre una clasificación aplicable a los niños con hipertensión pulmonar que se discutió en la reunión anual del PVRI que se llevó a cabo en Panamá en febrero de 2011.

  13. The association of genetic polymorphisms of hypoxia inducible factor-1 alpha and vascular endothelial growth factor with increased risk of chronic obstructive pulmonary disease: A case-control study.

    Science.gov (United States)

    Yu, Zhen-Gang; Wang, Bing-Zhe; Cheng, Zhao-Zhong

    2017-09-01

    Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV1/predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV1/FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV1/FVC and FEV1/pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk. Copyright © 2017. Published by Elsevier Taiwan.

  14. Sclerosing haemangioma arising within extralobar pulmonary sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Ahmetoglu, Ali; Kosucu, Polat; Guemele, Halit Resit [Department of Radiology, Farabi Hospital, Karadeniz Technical University, 61080 Trabzon (Turkey); Imamoglu, Mustafa; Cay, Ali [Department of Paediatric Surgery, Farabi Hospital, Karadeniz Technical University, Trabzon (Turkey); Reis, Abdulkadir [Department of Pathology, Farabi Hospital, Karadeniz Technical University, Trabzon (Turkey)

    2003-09-01

    Extralobar pulmonary sequestration is a rare anomaly of abnormal pulmonary tissue without any communication to the bronchial tree. Sclerosing haemangioma is a rare lung tumour, generally seen in middle-aged women. The combination of these two rare pathologies has not been previously reported. We describe the CT and CT angiographic findings of sclerosing haemangioma arising within an extralobar pulmonary sequestration in a 2-year-old girl. (orig.)

  15. Functional diversity of photosynthetic light use of sixteen vascular epiphyte species under fluctuating irradiance in the canopy of a giant Virola michelii (Myristicaceae tree in the tropical lowland forest of French Guyana

    Directory of Open Access Journals (Sweden)

    Uwe eRascher

    2012-01-01

    Full Text Available Here we present the first study, in which a large number of different vascular epiphyte species were measured for their photosynthetic performance in the natural environment of their phorophyte in the lowland rainforest of French Guyana. More than 70 epiphyte species covered the host tree in a dense cover. Of these, the photosynthesis of 16 abundant species was analyzed intensely over several months. Moreover, the light environment was characterized with newly developed light sensors that recorded continuously and with high temporal resolution light intensity next to the epiphytes. Light intensity was highly fluctuating and showed great site specific spatio-temporal variations of photosynthetic photon flux. Using a novel computer routine we quantified the integrated light intensity the epiphytes were exposed to in a 3-hour window and we related this light intensity to measurements of the actual photosynthetic status. It could be shown that the photosynthetic apparatus of the epiphytes was well adapted to the quickly changing light conditions. Some of the epiphytes were chronically photoinhibited at pre-dawn and significant acute photoinhibition, expressed by a reduction of potential quantum efficiency (Fv/Fm30’, was observed during the day. By correlating (Fv/Fm30’ to the integrated and weighted light intensity perceived during the previous 3 hours, it became clear that acute photoinhibition was related to light environment prior to the measurements. Additionally photosynthetic performance was not determined by rain events, with the exception of an Aechmea species. This holds true for all the other 15 species of this study and we thus conclude that actual photosynthesis of these tropical epiphytes was determined by the specific and fluctuating light conditions of their microhabitat and cannot be simply attributed to light adapted ancestors.

  16. Functional Diversity of Photosynthetic Light Use of 16 Vascular Epiphyte Species Under Fluctuating Irradiance in the Canopy of a Giant Virola michelii (Myristicaceae) Tree in the Tropical Lowland Forest of French Guyana.

    Science.gov (United States)

    Rascher, Uwe; Freiberg, Martin; Lüttge, Ulrich

    2011-01-01

    Here we present the first study, in which a large number of different vascular epiphyte species were measured for their photosynthetic performance in the natural environment of their phorophyte in the lowland rainforest of French Guyana. More than 70 epiphyte species covered the host tree in a dense cover. Of these, the photosynthesis of 16 abundant species was analyzed intensely over several months. Moreover, the light environment was characterized with newly developed light sensors that recorded continuously and with high temporal resolution light intensity next to the epiphytes. Light intensity was highly fluctuating and showed great site specific spatio-temporal variations of photosynthetic photon flux. Using a novel computer routine we quantified the integrated light intensity the epiphytes were exposed to in a 3 h window and we related this light intensity to measurements of the actual photosynthetic status. It could be shown that the photosynthetic apparatus of the epiphytes was well adapted to the quickly changing light conditions. Some of the epiphytes were chronically photoinhibited at predawn and significant acute photoinhibition, expressed by a reduction of potential quantum efficiency (F(v)/F(m))(30'), was observed during the day. By correlating (F(v)/F(m))(30') to the integrated and weighted light intensity perceived during the previous 3 h, it became clear that acute photoinhibition was related to light environment prior to the measurements. Additionally photosynthetic performance was not determined by rain events, with the exception of an Aechmea species. This holds true for all the other 15 species of this study and we thus conclude that actual photosynthesis of these tropical epiphytes was determined by the specific and fluctuating light conditions of their microhabitat and cannot be simply attributed to light-adapted ancestors.

  17. Pulmonary edema: radiographic differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Dong Soo; Choi, Young Hi; Kim, Seung Cheol; An, Ji Hyun; Lee, Jee Young; Park, Hee Hong [Dankook Univ. College of Medicine, Chonan (Korea, Republic of)

    1997-04-01

    To evaluate the feasibility of using chest radiography to differentiate between three different etiologies of pulmonary edema. Plain chest radiographs of 77 patients, who were clinically confirmed as having pulmonary edema, were retrospectively reviewed. The patients were classified into three groups : group 1 (cardiogenic edema : n = 35), group 2 (renal pulmonary edema : n = 16) and group 3 (permeability edema : n = 26). We analyzed the radiologic findings of air bronchogram, heart size, peribronchial cuffing, septal line, pleural effusion, vascular pedicle width, pulmonary blood flow distribution and distribution of pulmonary edema. In a search for radiologic findings which would help in the differentiation of these three etiologies, each finding was assessed. Cardiogenic and renal pulmonary edema showed overlapping radiologic findings, except for pulmonary blood flow distribution. In cardiogenic pulmonary edema (n=35), cardiomegaly (n=29), peribronchial cuffing (n=29), inverted pulmonary blood flow distribution (n=21) and basal distribution of edema (n=20) were common. In renal pulmonary edema (n=16), cardiomegaly (n=15), balanced blood flow distribution (n=12), and central (n=9) or basal distribution of edema (n=7) were common. Permeability edema (n=26) showed different findings. Air bronchogram (n=25), normal blood flow distribution (n=14) and peripheral distribution of edema (n=21) were frequent findings, while cardiomegaly (n=7), peribronchial cuffing (n=7) and septal line (n=5) were observed in only a few cases. On plain chest radiograph, permeability edema can be differentiated from cardiogenic or renal pulmonary edema. The radiographic findings which most reliably differentiated these two etiologies were air bronchogram, distribution of pulmonary edema, peribronchial cuffing and heart size. Only blood flow distribution was useful for radiographic differentiation of cardiogenic and renal edema.

  18. What Is Vascular Disease?

    Science.gov (United States)

    ... Donors Corporate Sponsors Donor Privacy Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of ... steps to prevent vascular disease here. Understanding the Vascular System Your vascular system – the highways of the ...

  19. Pulmonary thromboembolism in children

    Energy Technology Data Exchange (ETDEWEB)

    Babyn, Paul S.; Gahunia, Harpal K. [Hospital for Sick Children, Department of Pediatric Diagnostic Imaging, Toronto, ON (Canada); Massicotte, Patricia [Stollery Children' s Hospital and University of Alberta, Departments of Pediatric Hematology and Cardiology, Edmonton, AB (Canada)

    2005-03-01

    Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions, malignancy, renal disease, foreign bodies or, uncommonly, intracranial venous sinus thrombosis, burns, or nonbacterial thrombotic endocarditis. Other types of embolism can occur uncommonly in childhood and need to be recognized, as the required treatment will vary. These include pulmonary cytolytic thrombi, foreign bodies, tumor and septic emboli, and post-traumatic fat emboli. No single noninvasive test for pulmonary embolism is both sensitive and specific. A combination of diagnostic procedures must be used to identify suspect or confirmed cases of PTE. This article reviews the risk factors, clinical presentation and treatment of pulmonary embolism in children. It also highlights the current diagnostic tools and protocols used to evaluate pulmonary embolism in pediatric patients. (orig.)

  20. Hematological disorders and pulmonary hypertension

    Science.gov (United States)

    Mathew, Rajamma; Huang, Jing; Wu, Joseph M; Fallon, John T; Gewitz, Michael H

    2016-01-01

    Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH. PMID:28070238

  1. 内皮抑制素对慢性阻塞性肺疾病肺血管重塑的影响%Effect of Endostar on pulmonary vascular remodeling in animal model of chronic obstructive pulmonarv disease

    Institute of Scientific and Technical Information of China (English)

    王昌明; 蒋明; 吕倩; 梁荣感; 李运千

    2011-01-01

    Objective To investigate the effect of Endostar on pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD). Methods 64 male SD rats were divided into healthy control, group A, chronic bronchitis group B, COPD group C,low oxygen with COPD group D. Intervention group included; Al (normal group) , Bl (chronic bronchitis intervented group) , Cl (COPD inter-vented group) , Dl (low oxygen with COPD intervented group). Animal models wwere made in the above intervention groups as the same as that in corresponding groups. Endostar 7. 5 mg ? M~ ? D ' ( 1. 25 mg/kg) was injected into the rats in each drug group from the third week. The saline water same dose of Endosta r was injected into the rat in Al group from the third week. The airway resistance and pulmonary he-modynamics were detected. HE staining was used to observe lung tissue pathological changes and VG + Victoria blue triple staining was used to observe the airway inflammation and pulmonary vascular remodeling in pathological changes. Immunohistochemistry was used to detect VEGF expression in rat lung tissue. ELISA was detected of VEGF expression in serum and RT-PCR was used to detect VEGF mRNA in lung tissue. Results Compared to the group A, the airway resistance, mean pulmonary arterial pressure (mPAP) in group C and D were higher than those of group A (P <0. 05) ; After Endostar intervention, the airway resistance, mPAP in group Cl , Dl were decreased than those of group C, D ( P < 0. 05). WT% , WA% value in group C, D were higher than those of group A, and WT% , WA% value were declined in these two groups after using Endostar. Serum VEGF level in group C and D were significantly higher than that of group A, and the VEGF concentration was significantly decreased in C, D groups than that of corresponding experimental group after using Endostar. VEGF mRNA of group B, C, D was gradually increased. The VEGF mRNA was gradually decreased in these three groups after using Endostar. Expression of

  2. Pulmonary hypertension

    Science.gov (United States)

    ... clots in the lung ( pulmonary embolism ) Heart failure Heart valve disease HIV infection Low oxygen levels in the blood for a long time (chronic) Lung disease, such as COPD or pulmonary fibrosis Medicines (for example, certain diet drugs) Obstructive sleep ...

  3. Pulmonary Edema

    Science.gov (United States)

    ... Accessed March 13, 2014. Pinto DS, et al. Pathophysiology of cardiogenic pulmonary edema. http://www.uptodate.com/ ... hvd/. Accessed March 10, 2014. What is pulmonary hypertension? National Heart, Lung, and Blood Institute. http://www. ...

  4. Pulmonary Fibrosis

    Science.gov (United States)

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This ... blood may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  5. Pulmonary Rehabilitation

    Science.gov (United States)

    ... shortness of breath and increase your ability to exercise. You may have heard that pulmonary rehabilitation is only for people with COPD (chronic obstructive pulmonary disease). We now know that ...

  6. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  7. The evolution of development of vascular cambia and secondary growth

    Science.gov (United States)

    Andrew Groover; Rachel Spicer

    2010-01-01

    Secondary growth from vascular cambia results in radial, woody growth of stems. The innovation of secondary vascular development during plant evolution allowed the production of novel plant forms ranging from massive forest trees to flexible, woody lianas. We present examples of the extensive phylogenetic variation in secondary vascular growth and discuss current...

  8. Treatment of pediatric pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Amy Hawkins

    2009-06-01

    Full Text Available Amy Hawkins, Robert TullohDepartment of Congenital Heart Disease, Bristol Royal Hospital for Children, Bristol UKAbstract: Pulmonary hypertension was once thought to be a rare condition and only managed in specialized centers. Now however, with the advent of echocardiography, it is found in many clinical scenarios, in the neonate with chronic lung disease, in the acute setting in the intensive care unit, in connective tissue disease and in cardiology pre- and postoperatively. We have a better understanding of the pathological process and have a range of medication which is starting to be able to palliate this previously fatal condition. This review describes the areas that are known in this condition and those that are less familiar. The basic physiology behind pulmonary hypertension and pulmonary vascular disease is explained. The histopathologic process and the various diagnostic tools are described and are followed by the current and future therapy at our disposal.Keywords: pulmonary hypertension, congenital heart disease, pulmonary vascular resistance, pulmonary vasodilators

  9. Pulmonary hypertension in dialysis patients.

    Science.gov (United States)

    Kosmadakis, George; Aguilera, Didier; Carceles, Odette; Da Costa Correia, Enrique; Boletis, Ioannis

    2013-01-01

    Pulmonary hypertension in end-stage renal disease patients is associated with significantly increased morbidity and mortality. The prevalence of pulmonary hypertension in dialysis patients is relatively high and varies in different studies from 17% to 49.53% depending on the mode of dialysis and other selection factors, such as the presence of other cardiovascular comorbidities. The etiopathogenic mechanisms that have been studied in relatively small studies mainly include arteriovenous fistula-induced increased cardiac output, which cannot be accomodated by, the spacious under normal conditions pulmonary circulation. Additionally, pulmonary vessels show signs of endothelial dysfunction, dysregulation of vascular tone due to an imbalance in vasoactive substances, and local as well as systemic inflammation. It is also believed that microbubbles escaping from the dialysis circuit can trigger vasoconstriction and vascular sclerosis. The non-specific therapeutic options that proved to be beneficial in pulmonary artery pressure reduction are endothelin inhibitors, phosphodiesterase inhibitor sildenafil, and vasodilatory prostaglandins in various forms. The specific modes of treatment are renal transplantation, size reduction or closure of high-flow arteriovenous fistulas, and transfer from hemodialysis to peritoneal dialysis-a modality that is associated with a lesser prevalence of pulmonary hypertension.

  10. Combined effect of aerosolized iloprost and oxygen on assessment of pulmonary vasoreactivity in children with pulmonary hypertension.

    Science.gov (United States)

    Elkiran, Ozlem; Karakurt, Cemşit; Koçak, Gülendam

    2014-06-01

    The evaluation of pulmonary vascular reactivity plays a significant role in the management of patients with pulmonary hypertension. Inhaled nitric oxide in combination with oxygen (O2) has become widely used as an agent for pulmonary vasodilator testing. However, inhaled nitric oxide is not available in many developing countries. Recently, aerosolized iloprost was suggested as an alternative to nitric oxide for this purpose. In the present study, aerosolized iloprost was used together with O2 in the pulmonary vasoreactivity test of children with severe pulmonary hypertension. Thus, the synergistic effect of both vasodilators was utilized without extending the duration of cardiac catheterization. The prospective cohort study registered a total of 16 children with severe pulmonary hypertension whose median age was 4.5 years. Hemodynamic parameters were quantified before and after the vasoreactivity test. Increased left-to-right shunt, pulmonary vascular resistance of 10% in the pulmonary vascular resistance and pulmonary-systemic vascular resistance ratio after the vasoreactivity test were accepted as a positive response. The data were analyzed using Wilcoxon signed-rank and the Mann-Whitney U tests. Eleven children gave a positive response to the vasoreactivity test, while 5 children did not respond. Pulmonary vascular resistance dropped from 9.98 ± 1.39 WU/m(2) to 5.08 ± 1.05 WU/m(2) (p=0.013) and the pulmonary-systemic vascular resistance ratio fell from 0.68 ± 0.08 to 0.32 ± 0.05 (p=0.003) in the children who were responsive. No side effects were observed related to iloprost administration. Administration of inhaled iloprost in combination with O2 for pulmonary vasoreactivity testing can be useful for correctly identifying pulmonary vasoreactivity without extending the duration of cardiac catheterization.

  11. [Physiopathology of pulmonary arterial hypertension. Cellular and molecular aspects].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc

    2005-02-12

    The combined effects of vasoconstriction, remodelling of the pulmonary vessel walls and in situ thrombosis contribute to the increase in pulmonary vascular resistance during pulmonary arterial hypertension. Vascular remodelling involves all the sheaths of the vessel wall and all the cell types of which it is composed (endothelial cells, smooth muscle cells, fibroblasts, inflammatory cells and platelets). Excessive vasoconstriction has been related to a defect in the function of expression of the potassium channels and endothelial dysfunction. This leads to chronic insufficiency in the production of vasodilators, notably nitrogen monoxide and prostacyclin and the excessive production of vasoconstrictors such as endotheline-1. These defects contribute to the increase in vascular tonus and pulmonary vascular remodelling and represent pertinent pharmacological targets. Certain growth factors, including those of the super-family of transforming growth factor beta, angiopoietine-1 and serotonin, may play a part in the pathogenesis of pulmonary arterial hypertension.

  12. Pulmonary vasculitis.

    Science.gov (United States)

    Lally, Lindsay; Spiera, Robert F

    2015-05-01

    Pulmonary vasculitis encompasses inflammation in the pulmonary vasculature with involved vessels varying in caliber from large elastic arteries to capillaries. Small pulmonary capillaries are the vessels most commonly involved in vasculitis affecting the lung. The antineutrophil cytoplasmic antibody-associated vasculitides, which include granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), are the small vessel vasculitides in which pulmonary vasculitis is most frequently observed and are the major focus of this review. Vasculitic involvement of the large pulmonary vessels as may occur in Behçet syndrome and Takayasu arteritis is also discussed.

  13. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    Science.gov (United States)

    Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen

    2016-10-01

    Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.

  14. Hemoptysis and pulmonary artery agenesis: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Majano, V.; Sobti, P.

    1985-08-01

    The combination of a pulmonary scintigram using radioactively labeled albumin macroaggregates (MAA) and a study of the circulation in the bronchial artery was performed in one patient. This noninvasive methodology showed that there was increased circulation to the vascular territory of the lung in which the pulmonary artery was missing. This could have resulted from abnormal communications between the bronchial artery and the pulmonary vessels or an increased blood supply to the right lung from bronchial arteries arising from the aorta. The absence of pulmonary circulation in the right lung was proved by the absence of radioactivity in the right lung after an intravenous injection of labeled albumin MAA.

  15. Fetal and postnatal pulmonary circulation in the Alto Andino.

    Science.gov (United States)

    Llanos, A J; Ebensperger, G; Herrera, E A; Reyes, R V; Pulgar, V M; Serón-Ferré, M; Díaz, M; Parer, J T; Giussani, D A; Moraga, F A; Riquelme, R A

    2011-03-01

    Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.

  16. Tree rings and the local environment

    Science.gov (United States)

    Kevin T. Smith

    2011-01-01

    The amount of wood produced by a tree each year depends on tree condition, genetic programming, and growing conditions. Wood is mature xylem, the result of inward cell divisions by the vascular cambium, the new cell generator located between the wood and the inner bark (phloem). In temperate climatic zones, where a spring and summer growing season alternates with...

  17. Enumerating Trees

    CERN Document Server

    Kucharczyk, Robert A

    2012-01-01

    In this note we discuss trees similar to the Calkin-Wilf tree, a binary tree that enumerates all positive rational numbers in a simple way. The original construction of Calkin and Wilf is reformulated in a more algebraic language, and an elementary application of methods from analytic number theory gives restrictions on possible analogues.

  18. VASCULAR SURGERY

    African Journals Online (AJOL)

    Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are linked to an increased risk of PE.2 .... tool for DVT in hospitalised patients, where higher scores.

  19. Vascular Dementia

    Science.gov (United States)

    ... that includes enjoyable activities well within the comfort zone of the person with vascular dementia. New situations, ... your cholesterol in check. A healthy, low-fat diet and cholesterol-lowering medications if you need them ...

  20. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  1. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  2. Diagnosing chronic thromboembolic pulmonary hypertension: current perspectives

    Directory of Open Access Journals (Sweden)

    Hadinnapola C

    2014-09-01

    Full Text Available Charaka Hadinnapola, Deepa Gopalan, David P Jenkins Papworth Hospital National Health Service Foundation Trust, Papworth Everard, Cambridge, United Kingdom Abstract: Chronic thromboembolic pulmonary hypertension is a rare and relatively poorly understood disease. It remains underdiagnosed and is often not recognized in primary and secondary care, as its symptoms are nonspecific and there are few clinical signs until late in the disease process. However, pulmonary endarterectomy (PEA offers a potential cure for patients with this type of pulmonary hypertension; therefore, it is important that they are identified and diagnosed in a timely manner. PEA is associated with a 2.2%–5% risk of significant morbidity and mortality, even in experienced PEA centers. Therefore, once chronic thromboembolic pulmonary hypertension is diagnosed, further assessment of operability and patient selection is crucial. Assessment of operability involves determining the distribution and burden of chronic thromboembolic disease, assessing pulmonary hemodynamics, and assessing the functional impairment of the patient. Ventilation perfusion scintigraphy is of value in screening for the presence of chronic thromboembolic disease. However, computer tomography pulmonary angiography and magnetic resonance pulmonary angiography are now increasingly used to image the vascular occlusions directly. This allows assessment of the surgically accessible disease burden. Some centers still advocate conventional selective pulmonary angiography for the latter. Right-heart catheterization remains the gold standard for assessing pulmonary hemodynamics. Higher pulmonary vascular resistances are associated with poorer outcomes as well as increased risks at the time of surgery. This is in part because of the presence of more distal chronic thromboembolic material and distal pulmonary artery remodeling. However, in experienced centers, these patients are being operated on safely and with good

  3. [Pulmonary involvements of sarcoidosis].

    Science.gov (United States)

    Ohmichi, M; Hiraga, Y; Hirasawa, M

    1990-01-01

    We reported about intrathoracic changes and prognosis of 686 patients with sarcoidosis diagnosed in our hospital between 1963 and 1988. We evaluated CT findings in 135 patients with sarcoidosis and found pulmonary involvements in 81. We analyzed CT findings according to the classification by Tuengerthal which classified radiographic findings combining ILO classification of pneumoconiosis and characteristic findings of bronchovascular sheath with sarcoidosis. The CT findings were as follows: small opacities (44 out of 81 cases, 54.3%), large opacities (37 cases, 46.7%). Additional findings were as follows: peribronchial marking (42 cases, 51.9%), contraction (17 cases, 21.0%), pleural involvement (9 cases, 11.1%), bulla (5 cases, 6.2%). The characteristic CT findings of serious sarcoidosis were extasis of bronchus, thickening of the bronchial wall, unclearness of vascular shadow, atelectasis and thickening of pleura. Concerning the prognosis of pulmonary involvement, according to age, patients younger than 30 years old at initial diagnosis were better than those of 30 years and over in terms of disappearance of pulmonary involvements. According to stage, patients of stage I and stage II were better than those of stage III. Among the patients we were able to observe chest X-ray findings during five years according to the character of shadow, ill-defined shadow of small opacities and rounded shadows of large opacities had a higher disappearance rate of pulmonary involvements than irregular shadows of large opacities, atelectasis and contraction.

  4. Tree compression with top trees

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Landau, Gad M.;

    2015-01-01

    We introduce a new compression scheme for labeled trees based on top trees. Our compression scheme is the first to simultaneously take advantage of internal repeats in the tree (as opposed to the classical DAG compression that only exploits rooted subtree repeats) while also supporting fast...

  5. Tree compression with top trees

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Landau, Gad M.

    2013-01-01

    We introduce a new compression scheme for labeled trees based on top trees [3]. Our compression scheme is the first to simultaneously take advantage of internal repeats in the tree (as opposed to the classical DAG compression that only exploits rooted subtree repeats) while also supporting fast...

  6. Tree compression with top trees

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Landau, Gad M.

    2015-01-01

    We introduce a new compression scheme for labeled trees based on top trees. Our compression scheme is the first to simultaneously take advantage of internal repeats in the tree (as opposed to the classical DAG compression that only exploits rooted subtree repeats) while also supporting fast...

  7. Pulmonary Hypertension in Pregnancy: Critical Care Management

    Directory of Open Access Journals (Sweden)

    Adel M. Bassily-Marcus

    2012-01-01

    Full Text Available Pulmonary hypertension is common in critical care settings and in presence of right ventricular failure is challenging to manage. Pulmonary hypertension in pregnant patients carries a high mortality rates between 30–56%. In the past decade, new treatments for pulmonary hypertension have emerged. Their application in pregnant women with pulmonary hypertension may hold promise in reducing morbidity and mortality. Signs and symptoms of pulmonary hypertension are nonspecific in pregnant women. Imaging workup may have undesirable radiation exposure. Pulmonary artery catheter remains the gold standard for diagnosing pulmonary hypertension, although its use in the intensive care unit for other conditions has slowly fallen out of favor. Goal-directed bedside echocardiogram and lung ultrasonography provide attractive alternatives. Basic principles of managing pulmonary hypertension with right ventricular failure are maintaining right ventricular function and reducing pulmonary vascular resistance. Fluid resuscitation and various vasopressors are used with caution. Pulmonary-hypertension-targeted therapies have been utilized in pregnant women with understanding of their safety profile. Mainstay therapy for pulmonary embolism is anticoagulation, and the treatment for amniotic fluid embolism remains supportive care. Multidisciplinary team approach is crucial to achieving successful outcomes in these difficult cases.

  8. 分类决策树辅助CT诊断孤立性肺结节的方法学研究%Classification decision tree in CT imaging:application to the differential diagnosis of solitary pulmonary nodules

    Institute of Scientific and Technical Information of China (English)

    马红霞; 郭玉林; 王秋萍; 刘敏; 强永乾; 郭晓娟; 郭佑民; 陈起航

    2008-01-01

    目的 应用分类与回归决策树(CART)算法构建CT显像鉴别良恶性孤立性肺结节(SPN)预测模型,探讨数据挖掘技术在SPN影像诊断中的应用价值.方法 分别提取12个临床指标和22个CT征象指标作为CART预测SPN良恶性的输入指标.连续性纳入自2003年7月至2006年7月间经病理证实的SPN,且术前行CT检查的患者116例,其中良性结节62例,恶性结节54例.采用CART建立用于预测良恶性SPN的分类决策树模型,并通过交互印证的方法计算该模型的诊断准确性.同时设低年资医师诊断组和高年资医师诊断组,采用盲法进行独立阅片判断SPN的良恶性.采用受试者操作特征(ROC)曲线比较3组间的诊断效能.结果 (1)成功建立了能够判断SPN良恶性的CART诊断模型,其中含有8条诊断规则,最低相对错误代价为0.199,CART对SPN具有决策意义的最重要的前3位决策指标为结节的毛刺征、患者年龄和病灶部位.(2)CART、高年资医师和低年资医师对SPN良恶性诊断的ROC曲线下面积分别为0.910±0.029、0.827±0.038、0.612±0.052.CART与低年资医师ROC曲线下面积差(DBF)=0.297,P<0.01;与高年资医师DBF=0.083,P<0.05;高年资医师与低年资医师DBF=0.214,P<0.01.CART诊断效能高于高年资医师和低年资医师,高年资医师高于低年资医师.结论 CART是具有强大学习能力的数据挖掘工具,可以对SPN的良恶性进行正确判断,为实现人工智能在影像诊断中的应甩提供重要的方法学依据.%Objective To establish classification and regression tree (CART) for differentiating benign from malignant solitary pulmonary nudules (SPN).Methods One hundred and sixteen consecutive cases with 116 solitary pulmonary nodules,which finally were pathologically proven 54 malignant nodules and 62 benign nodules,were prospectively registered in this research.Twelve clinical presentations and 22 CT findings were collected as predictors.A classification tree

  9. Fundamentals of management of acute postoperative pulmonary hypertension.

    Science.gov (United States)

    Taylor, Mary B; Laussen, Peter C

    2010-03-01

    In the last several years, there have been numerous advancements in the field of pulmonary hypertension as a whole, but there have been few changes in the management of children with pulmonary hypertension after cardiac surgery. Patients at particular risk for postoperative pulmonary hypertension can be identified preoperatively based on their cardiac disease and can be grouped into four broad categories based on the mechanisms responsible for pulmonary hypertension: 1) increased pulmonary vascular resistance; 2) increased pulmonary blood flow with normal pulmonary vascular resistance; 3) a combination of increased pulmonary vascular resistance and increased blood flow; and 4) increased pulmonary venous pressure. In this review of the immediate postoperative management of pulmonary hypertension, various strategies are discussed including medical therapies, monitoring, ventilatory strategies, and weaning from these supports. With early recognition of patients at particular risk for severe pulmonary hypertension, management strategies can be directed at preventing or minimizing hemodynamic instability and thereby prevent the development of ventricular dysfunction and a low output state.

  10. Pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Lauro Martins Júnior

    2014-12-01

    Full Text Available Pulmonary hypertension is a pathological condition associated with various diseases, which must be remembered by the physicians, since early diagnosis may anticipate and avoid dangerous complications and even death if appropriate measures were not taken. The relationship with chronic obstructive pulmonary disease (COPD, important pathological process that is in increasing prevalence in developing countries, and leading position as cause of death, emphasizes its importance. Here are presented the classifications, pathophysiology, and general rules of treatment of pulmonary hypertension.

  11. [Pulmonary artery sling and single ventricle treated with a simultaneous operation of slide tracheoplasty, left pulmonary artery reimplantation, and bidirectional cavo-pulmonary shunt].

    Science.gov (United States)

    Kawahito, Tomohisa; Takano, Shinji; Egawa, Yoshiyasu; Iwamura, Yoshinobu; Nakahara, Yasuo; Nii, Akira; Ohnishi, Tatsuya; Miyagi, Yuhichi; Terada, Kazuya; Ohta, Akira

    2013-07-01

    Pulmonary artery sling is frequently combined with tracheal stenosis, and occasionally combined with congenital heart defects. However, there are few reports of successfully treated cases that were combined with single ventricle. In this article, we report a successfully treated case of pulmonary artery sling combined with tracheal stenosis, single ventricle, pulmonary atresia, vascular ring, and bilateral superior vena cava. A male infant was referred to our hospital for central cyanosis, and was diagnosed with single ventricle (tricuspid stenosis, multiple ventricular septal defect, and hypoplastic right ventricle)with pulmonary atresia by echocardiogram. Tracheal stenosis was shown at cardiac catheterization. Pulmonary artery sling and tracheal diverticulum were diagnosed by computed tomography (CT) and magnetic resonance imaging(MRI)examination. Furthermore, the patient was complicated by vascular ring, which consisted of right aortic arch, an aberrant left subclavian artery, and patent ductus arteriosus, and this ductus arteriosus was connected to the left subclavian artery and pulmonary arterial trunk. After 6 months of medical treatment, including continuous infusion of prostaglandin, re-evaluation was performed by cardiac catheterization. We considered that bidirectional cavo-pulmonary shunt was appropriate for the patient since his pulmonary vasculature had matured well. An operation was performed under the use of cardio-pulmonary bypass. Release of vascular ring by division of the ductus, bilateral bidirectional cavo-pulmonary shunt, and a slide tracheoplasty for tracheal stenosis were performed simultaneously. His recovery was uneventful, and he is currently waiting to receive a Fontan-type operation.

  12. Vessel tree extraction using locally optimal paths

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; van Ginneken, Bram; de Bruijne, Marleen

    2010-01-01

    This paper proposes a method to extract vessel trees by continually extending detected branches with locally optimal paths. Our approach uses a cost function from a multi scale vessel enhancement filter. Optimal paths are selected based on rules that take into account the geometric characteristics...... of the vessel tree. Experiments were performed on 10 low dose chest CT scans for which the pulmonary vessel trees were extracted. The proposed method is shown to extract a better connected vessel tree and extract more of the small peripheral vessels in comparison to applying a threshold on the output...

  13. Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients

    Directory of Open Access Journals (Sweden)

    Quarck Rozenn

    2012-03-01

    Full Text Available Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH is associated with proximal pulmonary artery obstruction and vascular remodeling. We hypothesized that pulmonary arterial smooth muscle (PASMC and endothelial cells (PAEC may actively contribute to remodeling of the proximal pulmonary vascular wall in CTEPH. Our present objective was to characterize PASMC and PAEC from large arteries of CTEPH patients and investigate their potential involvement in vascular remodeling. Methods Primary cultures of proximal PAEC and PASMC from patients with CTEPH, with non-thromboembolic pulmonary hypertension (PH and lung donors have been established. PAEC and PASMC have been characterized by immunofluorescence using specific markers. Expression of smooth muscle specific markers within the pulmonary vascular wall has been studied by immunofluorescence and Western blotting. Mitogenic activity and migratory capacity of PASMC and PAEC have been investigated in vitro. Results PAEC express CD31 on their surface, von Willebrand factor in Weibel-Palade bodies and take up acetylated LDL. PASMC express various differentiation markers including α-smooth muscle actin (α-SMA, desmin and smooth muscle myosin heavy chain (SMMHC. In vascular tissue from CTEPH and non-thromboembolic PH patients, expression of α-SMA and desmin is down-regulated compared to lung donors; desmin expression is also down-regulated in vascular tissue from CTEPH compared to non-thromboembolic PH patients. A low proportion of α-SMA positive cells express desmin and SMMHC in the neointima of proximal pulmonary arteries from CTEPH patients. Serum-induced mitogenic activity of PAEC and PASMC, as well as migratory capacity of PASMC, were increased in CTEPH only. Conclusions Modified proliferative and/or migratory responses of PASMC and PAEC in vitro, associated to a proliferative phenotype of PASMC suggest that PASMC and PAEC could contribute to proximal vascular remodeling in CTEPH.

  14. Thoracic exploration for the diagnosis of multiple pulmonary vein varices: case report

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xun; HAN Hong-li; SHI Zhen-liang

    2007-01-01

    @@ Pulmonary vein varix, congenital or acquired dilation of the pulmonary vein, is a rare vascular abnormality.This disease often presents as a pulmonary mass on chest roentgenography, and pulmonary angiography, computed tomography (CT), or magnetic resonance imaging (MRI)is considered necessary for diagnosis.1 The diagnosis of the disease by thoracic exploration is rare because the present case was diagnosed as a pulmonary arteriovenous fistula before operation.

  15. Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis

    NARCIS (Netherlands)

    White, Kevin; Dempsie, Yvonne; Caruso, Paola; Wallace, Emma; McDonald, Robert A; Stevens, Hannah; Hatley, Mark E; Van Rooij, Eva; Morrell, Nicholas W; MacLean, Margaret R; Baker, Andrew H

    2014-01-01

    Pulmonary endothelial cell apoptosis is a transient, yet defining pathogenic event integral to the onset of many pulmonary vascular diseases such as pulmonary hypertension (PH). However, there is a paucity of information concerning the molecular pathway(s) that control pulmonary arterial endothelial

  16. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Intensive care management of pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    M. Ali Al-Azem

    2014-01-01

    Full Text Available Pulmonary hypertension (PH in the Intensive Care Unit (ICU may be due to preexisting pulmonary vascular lung disease, liver disease, or cardiac diseases. PH also may be caused by critical illnesses, such as acute respiratory distress syndrome (ARDS, acute left ventricular dysfunction and pulmonary embolism, or may occur after cardiac or thoracic surgery. Regardless of the underlying cause of PH, the final common pathway for hemodynamic deterioration and death is RV failure, which is the most challenging aspect of patient management. Therapy is thus aimed at acutely relieving RV overload by decreasing PVR and reversing RV failure with pulmonary vasodilators and inotropes.

  17. Endothelial follistatin-like 1 regulates the maturation of the pulmonary vasculature by modulating BMP/SMAD signaling

    NARCIS (Netherlands)

    Tania, Navessa Padma; Maarsingh, Harm; Bos, Sophie T.; Mattiotti, Andrea; Prakash, Stuti; Timens, Wim; Schmidt, Martina; Van Den Hoff, Maurice; Gosens, Reinoud

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that is characterized by vascular remodeling and sustained vasoconstriction which consequently lead to high blood pressure in the pulmonary vasculature and right ventricle remodeling. Altered bone morphogenetic protein (BMP) signaling ha

  18. 西地那非抑制高肺血流肺动脉高压大鼠肺血管重构和上调肺血管Kv1.5mRNA表达%Sildenafil inhibits pulmonary vascular remodeling and up-regulates voltage-gated potassium channel Kv1.5 mRNA expression in secondary pulmonary hypertension due to left-to-right shunt in rats

    Institute of Scientific and Technical Information of China (English)

    胡蕾; 谈林华; 林隆; 何小军; 范佳杰

    2010-01-01

    Objective To investigate the effects of sildenafil on pulmonary vascular remodeling and voltage-gated potassium channeI Kv1.5 mRNA expression of pulmonary vasculature in secondary pulmonary hypertension due to left-to-right shunt in rats.Methods Male twenty-seven SD rats were randomly divided into sham group(n=9),shunt group(n=9)and shunt+sildenafil group(n=9).A left-to-right shunt was established on shunt group and shunt+sildenafil group rats by making fistula between abdominal aorta and inferior vena cava.Rats of the shunt+sildenafil group were administered sildenafil by gastric gavage at a dose of 10 mg·kg-1·d-1;whereas the rats of the sham group and the shunt group were fed with the same amount of saline. Eleven weeks later,mean pulmonary artery pressure(mPAP)and systolic pulmonary artery pressure(sPAP)were measured.The ratio of right ventricular mass to left ventricular plus septal mass[Rv/(LV+S)]was alao calculated and taken as a marker of the severity of right ventricular hypertrophy.The pathological changes of pulmonary vasculature were evaluated by calculating the relative medial thickness(RMT) of middle and small pulmonary muscularized arteries.The voltage-gated potassium channel Kv1.5 mRNA expression of pulmonary vasculature was qnantifieel using real-time PCIL Results Compared with the rats of sham grouD.the rats of shunt group had higher mPAP,sPAP,RV/(LV+S)ratio,and RMT of middie and small pulmonary muscularized(P0.05).Conclusions Sidenafil inhibits pulmonary vascular remodeling and up-regulates Kv1.5 mRNA expression in rats with secondary pulmonary hypertension due to left-to-right shunt.%目的 观察高肺血流肺动脉高压大鼠肺血管结构重建和肺血管电压依从钾通道Kv1.5mRNA表达变化,探讨口服西地那非对高肺血流肺动脉高压大鼠肺血管重构及肺血管电压依从钾通道Kv1.5mRNA表达的影响.方法 将27只雄性SD大鼠随机分为对照组(n=9)、分流组(n=9)、分流+西地那非组(n=9).后两

  19. Context trees

    OpenAIRE

    Ganzinger, Harald; Nieuwenhuis, Robert; Nivela, Pilar

    2001-01-01

    Indexing data structures are well-known to be crucial for the efficiency of the current state-of-the-art theorem provers. Examples are \\emph{discrimination trees}, which are like tries where terms are seen as strings and common prefixes are shared, and \\emph{substitution trees}, where terms keep their tree structure and all common \\emph{contexts} can be shared. Here we describe a new indexing data structure, \\emph{context trees}, where, by means of a limited kind of conte...

  20. Two Trees

    OpenAIRE

    Cochrane, John. H.; Longstaff, Francis A.; Santa-Clara, Pedro

    2004-01-01

    We solve a model with two “Lucas trees.†Each tree has i.i.d. dividend growth. The investor has log utility and consumes the sum of the two trees’ dividends. This model produces interesting asset-pricing dynamics, despite its simple ingredients. Investors want to rebalance their portfolios after any change in value. Since the size of the trees is fixed, however, prices must adjust to offset this desire. As a result, expected returns, excess returns, and return volatility all vary throug...

  1. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  2. HIF2α–arginase axis is essential for the development of pulmonary hypertension

    Science.gov (United States)

    Cowburn, Andrew S.; Crosby, Alexi; Macias, David; Branco, Cristina; Colaço, Renato D. D. R.; Southwood, Mark; Toshner, Mark; Crotty Alexander, Laura E.; Morrell, Nicholas W.; Chilvers, Edwin R.; Johnson, Randall S.

    2016-01-01

    Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. The rise in right ventricular systolic pressure (RVSP) normally observed following chronic hypoxic exposure was absent in mice with pulmonary endothelial HIF-2α deletion. The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia. PMID:27432976

  3. Vascular Disease Foundation

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  4. What Is Vascular Disease?

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  5. Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    David Jenkins

    2017-03-01

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a type of pulmonary hypertension, resulting from fibrotic transformation of pulmonary artery clots causing chronic obstruction in macroscopic pulmonary arteries and associated vascular remodelling in the microvasculature. Pulmonary endarterectomy (PEA offers the best chance of symptomatic and prognostic improvement in eligible patients; in expert centres, it has excellent results. Current in-hospital mortality rates are 90% at 1 year and >70% at 10 years. However, PEA, is a complex procedure and relies on a multidisciplinary CTEPH team led by an experienced surgeon to decide on an individual's operability, which is determined primarily by lesion location and the haemodynamic parameters. Therefore, treatment of patients with CTEPH depends largely on subjective judgements of eligibility for surgery by the CTEPH team. Other controversies discussed in this article include eligibility for PEA versus balloon pulmonary angioplasty, the new treatment algorithm in the European Society of Cardiology/European Respiratory Society guidelines and the definition of an “expert centre” for the management of this condition.

  6. Pulmonary gangrene as a complication of mucormycosis

    Energy Technology Data Exchange (ETDEWEB)

    Zagoria, R.J.; Choplin, R.H.; Karstaedt, N.

    1985-06-01

    Pulmonary gangrene, a rare complication of pneumonia occurs when vascular thrombosis leads to necrosis of a large portion of lung. The devitalized lung is then sloughed into a cavity, resulting in a characteristic radiographic appearance. The previously reported cases of pulmonary gangrene have been associated with either bacterial or tuberculous pneumonia; the authors describe a case resulting from mucormycosis. In addition to the plain-film findings, the computed tomographic (CT) appearance is described.

  7. Epistatic interactions in idiopathic pulmonary arterial hypertension

    OpenAIRE

    Shivani Vadapalli; M.L Satyanarayana; Chaitra, K.L.; H Surekh Rani; Sastry, B.K.S.; Pratibha Nallari

    2012-01-01

    Background : Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensiona...

  8. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Adel Boueiz

    2014-01-01

    In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection.

  9. Chronic Thromboembolic Pulmonary Hypertension: Treat the Patient Not the Haemodynamics

    Directory of Open Access Journals (Sweden)

    Ben Dunne

    2012-01-01

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a disabling condition that is being increasingly recognised. It is unique as a cause of pulmonary hypertension in that it is surgically curable. We wish to highlight the importance of recognition and early referral of any patient who may have CTEPH even in the absence of resting pulmonary hypertension as excellent results can be achieved by restoring pulmonary vascular anatomy, reducing exercise-induced pulmonary hypertension, and reducing dead-space ventilation. We present a case that illustrates these points and discuss our experience as a referral centre for CTEPH.

  10. The arterial load in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    A. Vonk-Noordegraaf

    2010-09-01

    Full Text Available The anatomical differences between the pulmonary and systemic arterial system are the main cause of the difference in distribution of compliance. In the pulmonary arterial system compliance is distributed over the entire arterial system, and stands at the basis of the constancy of the RC-time. This distribution depends on the number of peripheral vessels, which is ∼8–10 times more in the pulmonary system than the systemic tree. In the systemic arterial tree the compliance is mainly located in the aorta (80% of total compliance in thoracic-abdominal aorta. The constant RC-time in the pulmonary bed results in proportionality of systolic and diastolic pressure with mean pressure and, in turn, in the constant ratio of oscillatory and mean power.

  11. Modulation of pulmonary vasomotor tone in the fetus and neonate

    OpenAIRE

    2001-01-01

    Abstract The high pulmonary vascular resistance (PVR) of atelectatic, hypoxic, fetal lungs limits intrauterine pulmonary blood flow (PBF) to less than 10% of combined right and left ventricular output. At birth, PVR decreases precipitously to accommodate the entire cardiac output. The present review focuses on the role of endothelium-derived nitric oxide (NO), prostacyclin, and vascular smooth muscle potassium channels in mediating the decrease in PVR that occurs at birth, and in maintaining ...

  12. Pulmonary considerations in the immunocompromised patient.

    Science.gov (United States)

    Belleza, Walter G; Browne, Brian

    2003-05-01

    The compromised patient who presents to the emergency department with pulmonary complaints is becoming a common occurrence. An immunocompromised state can result from a disease process such as HIV or from medications used to prevent graft rejection in solid organ recipients or to treat conditions such as collagen vascular disease. The emergency department physician should be familiar with the more common complications that can afflict this unique patient group. This article addresses the presentation, evaluation, and treatment of the more common pulmonary complications that can occur in solid organ transplant recipients, cancer patients, patients suffering from collagen vascular disease, and patients with HIV disease.

  13. Talking Trees

    Science.gov (United States)

    Tolman, Marvin

    2005-01-01

    Students love outdoor activities and will love them even more when they build confidence in their tree identification and measurement skills. Through these activities, students will learn to identify the major characteristics of trees and discover how the pace--a nonstandard measuring unit--can be used to estimate not only distances but also the…

  14. Recent trends in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Rajagopalan Natarajan

    2011-01-01

    Full Text Available Pulmonary hypertension is a serious and unrelenting pulmonary vascular disorder that affects the functional quality of patients and significantly decreases their life span. If diagnosed early, with the number of new therapeutic options that are available, a better quality of life can be provided for a protracted length of time. It is likely that the available treatment will change the natural course of the disease and perhaps prolong survival. As symptoms are often subtle in the early stages of the disease it is imperative that physicians are aware of the manifestations of this condition. A thorough investigation of patients suspected of this condition is essential so that appropriate treatment can be initiated promptly. The routine workup of a patient suspected to have pulmonary hypertension could easily be carried out in any well-equipped peripheral hospital in many affluent and advanced countries. However, it must be mentioned that in some less advanced countries the necessary work up can only be done in major teaching hospitals. Both pulmonologists and cardiologists should be aware of the pathophysiology of pulmonary arterial hypertension, the workup and the treatment options that are available. Patients with refractory pulmonary hypertension should be referred to these research centers for enrolment into any ongoing drug trials as well as for evaluation for heart−lung, single lung, or double lung transplantation. This paper is primarily aimed at pulmonologists and cardiologists taking care of these patients. Unless indicated otherwise this paper mainly deals with WHO group 1 pulmonary hypertension which is designated pulmonary arterial hypertension. Extensive review of the literature spanning the last 30 years was made through Medline using titles such as primary pulmonary hypertension, pulmonary arterial hypertension, secondary pulmonary hypertension, and pulmonary vascular diseases.

  15. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)

    1998-06-02

    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  16. Agents Which Mediate Pulmonary Edema

    Science.gov (United States)

    1990-12-01

    directly the effect of mediators in the lavage on pulmonary vascular endothelium using endothelial cell line methods, as well as isolated perfused lungs...inte;wvention and/or protection from pathological chang6s. 8 1 MATERIALS AND METHODS Bronchoalveolar Lavage: The lavage procedure was performed through...have changed our 14 I technique to the following: 1 ) animals are lightly anesthetized with 30 mg/kg sodium arnytal and a #7.5 - 8 F polyvinyl

  17. Apoptosis-based therapy to treat pulmonary arterial hypertension

    Science.gov (United States)

    Suzuki, Yuichiro J.; Ibrahim, Yasmine F.; Shults, Nataliia V.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is rare, but patients who are diagnosed with this disease still suffer from a lack of satisfactory treatment strategies to prolong survival. While currently approved drugs for PAH have some benefits, these vasodilators only have limited efficacy for eliminating pulmonary vascular remodeling and reducing mortality. Thus, our laboratory has been exploring the use of aggressive drugs, which are capable of causing apoptotic cell death, to treat PAH. We have so far found that three classes of anti-tumor agents, including anthracyclines, taxanes, and proteasome inhibitors, are capable of reducing pulmonary vascular thickness in rats with PAH. These drugs kill cells in remodeled pulmonary vessels without affecting the normal, healthy pulmonary vasculature, revealing that proliferating vascular cells in PAH patients are more sensitive to drug-induced apoptosis compared to the differentiated phenotype that is physiologically important for smooth muscle contraction. Since many apoptosis-inducing drugs cause cardiotoxicity in cancer patients, and because PAH patients already have a weakened heart, we focus on finding biological mechanisms that may reverse pulmonary vascular remodeling without promoting cardiotoxicity. We found two agents, dexrazoxane and pifithrin-α, that selectively inhibit cardiac muscle apoptosis without affecting the drug-induced apoptosis of the proliferating pulmonary vascular cells. Thus, we propose that the addition of apoptosis-inducing drugs and cardioprotectants to PAH therapies may be effective in treating patients and preventing right heart failure.

  18. Advances in the management of pediatric pulmonary hypertension.

    Science.gov (United States)

    Oishi, Peter; Datar, Sanjeev A; Fineman, Jeffrey R

    2011-09-01

    Pulmonary hypertension is a rare disease in neonates, infants, and children, and is associated with substantial morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority of research is focused specifically on neonatal and pediatric populations. Although therapeutic options have increased over the past several decades, they remain limited. In advanced pulmonary hypertension, progressive pulmonary vascular functional and structural changes ultimately cause increased pulmonary vascular impedance, right-ventricular failure, and death. Management includes the prevention and/or treatment of active pulmonary vasoconstriction, the support of right-ventricle function, treatment of the underlying disease (if possible), and the promotion of regressive remodeling of structural pulmonary vascular changes. Most currently available therapies augment or inhibit factors, or mediators of their downstream signaling cascades, that originate in the pulmonary vascular endothelium. These pathways include nitric-oxide/cyclic guanosine monophosphate (cGMP), prostacyclin, and endothelin-1. The ability to reverse advanced structural changes remains an as yet unattained goal. This paper reviews the epidemiology, pathophysiology, current treatments, and emerging therapies related to neonatal and pediatric pulmonary hypertension.

  19. Lung Aplasia with Pulmonary Artery Sling Like Anomaly

    Directory of Open Access Journals (Sweden)

    Onur Isik

    2016-04-01

    Full Text Available Unilateraly pulmonary agenesis is an extremely rare documented congenital anomaly. It may be defined as total absence of the pulmonary parencilyma, its vascular supporting structure, and bronchi beyond the bifurcation. The present case with reconstructed images is one of the different cases of agenesis reported in the literature.

  20. HIF-1α和VEGF在大鼠COPD中的表达及与肺血管重构的关系研究%Correlation between the expression of HIF-1α,VEGF and the pulmonary vascular remodeling in rats with COPD

    Institute of Scientific and Technical Information of China (English)

    吕倩; 王昌明; 蒋明; 梁荣感; 李运千

    2012-01-01

    目的 探讨HIF-1α、VEGF在COPD各阶段的表达情况及其与肺血管重构的关系.方法 24只♂SD大鼠随机分为3个组,每组8只.正常对照组(A):d 1、14气道内注入生理盐水,4 周后检测;慢支组(B):d 1、14经气道内注入脂多糖(LPS),200 μg/次,4周后检测;COPD组(C):d 1、14气道内注入LPS,200 μg/次,香烟烟雾暴露 1 h·d-1,共4周.各组测定气道阻力及平均肺动脉压力(mPAP).HE染色观察肺组织病理改变,VG+维多利亚蓝特殊染色检测肺血管重构指标:肺小动脉血管壁厚度与血管外径比(WT%)、血管壁面积与血管总面积比(WA%).RT-PCR、Western blot分别检测各组肺组织匀浆中HIF-1α、VEGF mRNA及蛋白表达情况.分析HIF-1α、VEGF的表达情况与肺血管重构指标的相关性.结果 ① 与A组相比,C组气道阻力、mPAP增加 (P<0.05).② VG+维多利亚蓝特殊染色显示C组WT%、WA%值高于A组.③ RT-PCR、Western blot结果显示,C组HIF-1α mRNA及蛋白表达较A组明显增加,B、C组VEGF mRNA表达逐渐增强,C组VEGF蛋白表达较A组明显增加.HIF-1α、VEGF表达情况均与肺血管重构指标WT%、WA%呈正相关,(P<0.05).结论 HIF-1α、VEGF与COPD的发病密切相关,其通过促进肺血管重构加重COPD的病情.改善缺氧状态及拮抗HIF-1α、VEGF的表达,尤其是在早期对VEGF的干预,可以减轻COPD的肺血管重构,减缓其到肺动脉高压的进展.%Aim To investigate the correlation between the expression of HIF-lα, VEGF in every stage of COPD and the pulmonary vascular remodeling in COPD. Methods 24 male SD rats were divided into 3 groups randomly. Healthy control group (group A): 0. 2 ml saline water was installed intratracheally once at Dayl and Dayl4 in all rats to prepare them for the test 4 weeks later. Chronic bronchitis group (group B):200 μg lipopolysaccharide(LPS) was installed intratracheally once at Dayl and Dayl4 in all rats to prepare them for the test 4 weeks later. COPD group (group C

  1. Rare Presentation of Left Lower Lobe Pulmonary Artery Dissection

    Directory of Open Access Journals (Sweden)

    René Hako

    2017-01-01

    Full Text Available Background. Pulmonary arterial dissection with chronic pulmonary arterial hypertension as its major cause is a very rare but life-threatening condition. In most cases the main pulmonary trunk is the affected site usually without involvement of its branches. Segmental or lobar pulmonary artery dissection is extremely rare. Case Presentation. We report a unique case of left lower lobe pulmonary artery dissection in a 70-year-old male, with confirmed chronic pulmonary hypertension. To confirm dissection MDCT pulmonary angiography was used. Multiplanar reformation (MPR images in sagittal, coronal, oblique sagittal, and curved projections were generated. This case report presents morphologic CT features of rare chronic left lobar pulmonary artery dissection associated with chronic pulmonary hypertension at a place of localised pulmonary artery calcification. CT pulmonary angiography excluded signs of thromboembolism and potential motion or flow artefacts. Conclusion. To the best of our knowledge, no case of lower lobe pulmonary artery dissection with flap calcification has been reported yet. CT imaging of the chest is a key diagnostic tool that is able to detect an intimal flap and a false lumen within the pulmonary arterial tree and is preferred in differential diagnosis of rare complications of sustained pulmonary arterial hypertension.

  2. World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology.

    Science.gov (United States)

    Prins, Kurt W; Thenappan, Thenappan

    2016-08-01

    Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by pathologic remodeling of the resistance pulmonary arteries, ultimately leading to right ventricular (RV) failure and death. In this article we discuss the definition of PAH, the initial epidemiology based on the National Institutes of Health Registry, and the updated epidemiology gleaned from contemporary registries, pathogenesis of pulmonary vascular dysfunction and proliferation, and RV failure in PAH. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pulmonary aspergilloma

    Science.gov (United States)

    ... grows on dead leaves, stored grain, bird droppings, compost piles, and other decaying vegetation. Cavities in the ... Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 8/31/2014 Updated by: Jatin M. ...

  4. Pulmonary tuberculosis

    Science.gov (United States)

    ... ray Pulmonary nodule, solitary - CT scan Miliary tuberculosis Tuberculosis of the lungs Erythema nodosum associated with sarcoidosis Respiratory system Tuberculin skin test References Fitzgerald DW, Sterling TR, Haas DW. ...

  5. Phylogenetic trees

    OpenAIRE

    Baños, Hector; Bushek, Nathaniel; Davidson, Ruth; Gross, Elizabeth; Harris, Pamela E.; Krone, Robert; Long, Colby; Stewart, Allen; WALKER, Robert

    2016-01-01

    We introduce the package PhylogeneticTrees for Macaulay2 which allows users to compute phylogenetic invariants for group-based tree models. We provide some background information on phylogenetic algebraic geometry and show how the package PhylogeneticTrees can be used to calculate a generating set for a phylogenetic ideal as well as a lower bound for its dimension. Finally, we show how methods within the package can be used to compute a generating set for the join of any two ideals.

  6. Potassium channels in pulmonary arterial hypertension.

    Science.gov (United States)

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.

  7. Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Hadinnapola, Charaka; Pepke-Zaba, Joanna

    2015-10-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.

  8. HIF2α–arginase axis is essential for the development of pulmonary hypertension

    OpenAIRE

    Cowburn, Andrew S.; Crosby, Alexi; Macias, David; Branco, Cristina; Colaço, Renato D. D. R.; Southwood, Mark; Toshner, Mark; Crotty Alexander, Laura E.; Morrell, Nicholas W.; Chilvers, Edwin R.; Johnson, Randall S.

    2016-01-01

    The expression of hypoxia-inducible factor (HIF)-2α in pulmonary endothelium of mice influences pulmonary vascular resistance and development of hypoxic pulmonary hypertension (PH) via an arginase-1–dependent mechanism. The HIF-2α:arginase-1 axis influences the homeostatic regulation of nitric oxide synthesis in the lung. Impaired generation of this vasoactive agent contributes to the initial development and vascular remodeling process of PH.

  9. Pulmonary hypertension

    OpenAIRE

    2016-01-01

    In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summaris...

  10. Pulmonary Agenesis.

    Science.gov (United States)

    Chawla, Rakesh K; Madan, Arun; Chawla, Aditya; Arora, Harsh Nandini; Chawla, Kiran

    2015-01-01

    Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.

  11. Pulmonary Edema

    OpenAIRE

    Tanser, Paul H.

    1981-01-01

    The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients.

  12. Reversal of experimental pulmonary hypertension by PDGF inhibition

    Science.gov (United States)

    Schermuly, Ralph Theo; Dony, Eva; Ghofrani, Hossein Ardeschir; Pullamsetti, Soni; Savai, Rajkumar; Roth, Markus; Sydykov, Akylbek; Lai, Ying Ju; Weissmann, Norbert; Seeger, Werner; Grimminger, Friedrich

    2005-01-01

    Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the disease. A 2-week treatment resulted in 100% survival, compared with only 50% in sham-treated rats. The changes in RV pressure, measured continuously by telemetry, and right heart hypertrophy were reversed to near-normal levels. STI571 prevented phosphorylation of the PDGF receptor and suppressed activation of downstream signaling pathways. Similar results were obtained in chronically hypoxic mice, which were treated with STI571 after full establishment of pulmonary hypertension. Moreover, expression of the PDGF receptor was found to be significantly increased in lung tissue from pulmonary arterial hypertension patients compared with healthy donor lung tissue. We conclude that STI571 reverses vascular remodeling and cor pulmonale in severe experimental pulmonary hypertension regardless of the initiating stimulus. This regimen offers a unique novel approach for antiremodeling therapy in progressed pulmonary hypertension. PMID:16200212

  13. Game tree algorithms and solution trees

    NARCIS (Netherlands)

    W.H.L.M. Pijls (Wim); A. de Bruin (Arie)

    1998-01-01

    textabstractIn this paper, a theory of game tree algorithms is presented, entirely based upon the concept of solution tree. Two types of solution trees are distinguished: max and min trees. Every game tree algorithm tries to prune nodes as many as possible from the game tree. A cut-off criterion in

  14. Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure

    Institute of Scientific and Technical Information of China (English)

    GAN Hui-li; ZHANG Jian-qun; LU Jia-kai; DONG Xiu-hua; HOU Xiao-tong; GAO Yuan-ming; ZHU Guang-fa

    2013-01-01

    Background Pulmonary thromboendarterectomy (PTE) has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH).This study aimed to characterize if pulmonary oligemia maneuver (POM) can alleviate pulmonary artery injury during PTE procedure.Methods A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure.They were retrospectively classified as non-POM group (group A,n=55) or POM group (group B,n=57).Members from group B received POM during rewarming period,whereas members from group A did not.Results There were three (5.45%) early deaths in group A,no death in group B (0) (Fisher's exact test,P=-0.118).Six patients in group A needed extracorporeal membrane oxygenation (ECMO) as life support after the PTE procedure,no patients in group B needed ECMO (Fisher's exact test,P=0.013).The patients in group B had a shorter intubation and ICU stay,lower mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR),higher partial pressure of oxygen in artery (PaO2) and arterial oxygen saturation (SaO2) and less medical expenditure than patients in group A.With a mean follow-up time of (58.3 ± 30.6) months,two patients in group A and one patient in group B died.The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance.Three months post the PTE procedure,the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance (P=-0.393).Conclusion POM can alleviate pulmonary artery injury,shorten ICU stay and intubation time,and lower down the rate of ECMO after PTE procedure.

  15. Electron Tree

    DEFF Research Database (Denmark)

    Appelt, Ane L; Rønde, Heidi S

    2013-01-01

    The photo shows a close-up of a Lichtenberg figure – popularly called an “electron tree” – produced in a cylinder of polymethyl methacrylate (PMMA). Electron trees are created by irradiating a suitable insulating material, in this case PMMA, with an intense high energy electron beam. Upon discharge......, during dielectric breakdown in the material, the electrons generate branching chains of fractures on leaving the PMMA, producing the tree pattern seen. To be able to create electron trees with a clinical linear accelerator, one needs to access the primary electron beam used for photon treatments. We...... appropriated a linac that was being decommissioned in our department and dismantled the head to circumvent the target and ion chambers. This is one of 24 electron trees produced before we had to stop the fun and allow the rest of the accelerator to be disassembled....

  16. Electron Tree

    DEFF Research Database (Denmark)

    Appelt, Ane L; Rønde, Heidi S

    2013-01-01

    The photo shows a close-up of a Lichtenberg figure – popularly called an “electron tree” – produced in a cylinder of polymethyl methacrylate (PMMA). Electron trees are created by irradiating a suitable insulating material, in this case PMMA, with an intense high energy electron beam. Upon discharge......, during dielectric breakdown in the material, the electrons generate branching chains of fractures on leaving the PMMA, producing the tree pattern seen. To be able to create electron trees with a clinical linear accelerator, one needs to access the primary electron beam used for photon treatments. We...... appropriated a linac that was being decommissioned in our department and dismantled the head to circumvent the target and ion chambers. This is one of 24 electron trees produced before we had to stop the fun and allow the rest of the accelerator to be disassembled....

  17. Torsed pulmonary sequestration presenting as a painful chest mass

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Ricki [University of Missouri-Kansas City, School of Medicine, Kansas City, MO (United States); Carver, Terrence W. [University of Missouri-Kansas City, School of Medicine, Kansas City, MO (United States); Children' s Mercy Hospital and Clinics, Department of Pulmonology, Kansas City, MO (United States); Rivard, Douglas C. [University of Missouri-Kansas City, School of Medicine, Kansas City, MO (United States); Children' s Mercy Hospital and Clinics, Department of Radiology, Kansas City, MO (United States)

    2010-08-15

    Pulmonary sequestration is a congenital abnormality that can be divided into intralobar or extralobar types. Both types are characterized by pulmonary tissue that does not communicate with the bronchial tree or pulmonary arteries and typically has its arterial supply arising from the descending aorta. We report a case of an 11-year-old girl with extralobar sequestration who presented with torsion causing abdominal pain and pleuritic chest pain. (orig.)

  18. Value of intravascular ultrasound in the assessment of pulmonary vascular properties and mortality in patients with pulmonary artery hypertension associated with connective tissue diseases%血管内超声评估结缔组织病相关性肺动脉高压患者肺血管性能和病死率

    Institute of Scientific and Technical Information of China (English)

    蔡宗烨; 李剑; 孙灵跃; 杨程德; 沈节艳; 何奔

    2015-01-01

    血管性能恶化,而其中PAH-CTD患者较其他类型的PAH患者好.PAH-CTD患者与其他类型的PAH患者的生存曲线未见明显差异,而在PAH患者中肺血管远端重塑型病死率较近端重塑型高.%Objective To investigate the value of intravascular ultrasound (IVUS) on assessing pulmonary vascular properties (PVPs) and its relationship with hemodynamics,and mortality rate in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD).Methods Patients (n =51) with highly suspected PAH-CTD were prospectively enrolled in our department between July 2011 and March 2014.All patients underwent right heart catheterization (RHC) and IVUS,and were divided into 3 groups:PAH-CTD (n =25),PAH due to other reasons (n =15),and non-PAH control group (n=11).Based on IVUS,PAH patients were divided into distal (n =22) and proximal (n =18) remodeling subtypes.A total of 408 pulmonary segments were detected by IVUS,and all patients were followed up to (19 ± 10) months.Results IVUS evidenced higher mean wall thickness (MWT) ((0.30 ± 0.02) mm and (0.33 ± 0.02) mm vs.(0.21 ± 0.02) rmm) and percentage of MWT (WTP) ((13.62 ± 0.59)% and (14.39 0.77)% vs.(9.57 ±0.97)%) values in PAH patients compared to control patients (all P < 0.01).Pulmonary vascular mechanical properties (PVMPs) including compliance ((8.85 ± 0.82) × 10 2-mm2/mmHg(1 mmHg =0.133 kPa) and (6.28 ± 0.65) × 10--2 mm2/mmHg vs.(41.59 ± 5.02) × 10-2 mm2-/mmHg,all P < 0.01),distensibility ((0.83 ± 0.09)%/mmHg and (0.55 ±0.06)%/mmHg vs.(3.16 ±0.38) %/mmHg,all P <0.01),elastic modulus ((169.25 ± 15.10) mmHg and (253.00 ± 22.11) mmHg vs.(43.78 ± 4.27) mmHg,all P < 0.01) and stiffness index 3 (4.19 ±0.41 and 5.18 ±0.34 vs.2.39 ±0.27,P <0.05 or 0.01) in PAH groups were all significantly worse than in control group (all P <0.01).An inverse exponential association was found between PVMPs and hemodynamics with R2 ranging from 0.544 to 0

  19. 血管外肺水指数和肺血管通透性指数与急性呼吸窘迫综合征严重程度的相关性%Correlation of severity classification of acute respiratory distress syndrome by the Berlin definition with extra vascular lung water index and pulmonary vascular permeability index

    Institute of Scientific and Technical Information of China (English)

    朱金源; 王晓红; 杨晓军; 王晓麒; 马希刚

    2015-01-01

    目的 探讨血管外肺水指数(EVLWI)和肺血管通透性指数(PVPI)与急性呼吸窘迫综合征(ARDS)柏林定义严重程度分级的关系.方法 对2012年7月至2014年7月收住宁夏医科大学总医院ICU符合ARDS柏林定义的患者70例,依据ARDS柏林定义分为轻度组(20例)、中度组(30例)和重度组(20例).记录患者入院24 h内急性生理和慢性健康状况(APACHEⅡ)评分和序贯器官衰竭(SOFA)评分,脉搏指示剂持续心排血量监测技术(PiCCO)监测3组患者入院1~4dEVLWI和PVPI,并绘制受试者工作特征曲线(ROC曲线),比较ROC曲线下面积(AUC).同步行血气分析并计算氧合指数(OI),分析EVLWI和PVPI与OI的相关性.结果 轻、中和重度组ARDS患者不同时相点EVLWI、PVPI及OI的组间比较:随着ARDS严重程度的分级加重,3组患者任一时相点EVLWI和PVPI均明显升高,OI明显降低(均P<0.05).轻、中和重度组ARDS患者EVLWI、PVPI及OI动态变化趋势的组内比较:轻度组1~4 d EVLWI和PVPI随时间逐渐下降(均P<0.05),中度组仅PVPI下降,EVLWI无明显下降(P>0.05),重度组EVLWI和PVPI均无明显下降趋势(均P>0.05),而3组1~4 d OI随时间变化均有升高(均P<0.01).3组ARDS患者1~4 d PVPI对预后评价的AUC分别为0.594、0.643、0.723和0.816,以入院第4天PVPI>2.95作为判断预后的最佳临界值,其敏感度为70%,特异度为92%.3组所有ARDS患者1~4 d EVLWI和PVPI与OI呈现明显的负相关[(r=-0.685,P=0.000)和(r=-0.631,P=0.000)].结论 EVLWI和PVPI能够良好的反映ARDS柏林定义严重程度分级,且PVPI的动态变化趋势优于EVLWI.%Objective To explore the correlation of severity classification of acute respiratory distress syndrome (ARDS) by the Berlin definition with extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI).Methods A total of 70 cases with ARDS at intensive care unit of our hospital from July 2012 to July 2014 were divided into three

  20. Computer-aided detection of pulmonary embolism in computed tomographic pulmonary angiography (CTPA): Performance evaluation with independent data sets

    OpenAIRE

    Zhou, Chuan; Chan, Heang-Ping; Sahiner, Berkman; Hadjiiski, Lubomir M.; Chughtai, Aamer; Patel, Smita; Wei, Jun; Cascade, Philip N.; Kazerooni, Ella A.

    2009-01-01

    The authors are developing a computer-aided detection system for pulmonary emboli (PE) in computed tomographic pulmonary angiography (CTPA) scans. The pulmonary vessel tree is extracted using a 3D expectation-maximization segmentation method based on the analysis of eigenvalues of Hessian matrices at multiple scales. A parallel multiprescreening method is applied to the segmented vessels to identify volume of interests (VOIs) that contained suspicious PE. A linear discriminant analysis (LDA) ...

  1. Toward a theory of statistical tree-shape analysis

    DEFF Research Database (Denmark)

    Feragen, Aasa; Lo, Pechin Chien Pau; de Bruijne, Marleen

    2013-01-01

    these advantages. Along with the theoretical framework we provide experimental proof-of-concept results on synthetic data trees as well as small airway trees from pulmonary CT scans. This way, we illustrate that our framework has promising theoretical and qualitative properties necessary to build a theory...

  2. Types of Pulmonary Hypertension

    Science.gov (United States)

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  3. Hydrogen sulfide and vascular relaxation

    Institute of Scientific and Technical Information of China (English)

    SUN Yan; TANG Chao-shu; DU Jun-bao; JIN Hong-fang

    2011-01-01

    Objective To review the vasorelaxant effects of hydrogen sulfide (H2S) in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved.Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms "hydrogen sulfide" and ""vascular relaxation".Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected.Results H2S plays an important role in the regulation of cardiovascular tone.The vasomodulatory effects of H2S depend on factors including concentration,species and tissue type.The H2S donor,sodium hydrosulfide (NarS),causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner.This effect was more pronounced than that observed in pulmonary arterial rings.The expression of KATP channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings.H2S is involved in the pathogenesis of a variety of cardiovascular diseases.Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases.The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the CI/HCO3 exchanger.It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation.Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.

  4. Dissimilarity-based classification of anatomical tree structures

    DEFF Research Database (Denmark)

    Sørensen, Lauge Emil Borch Laurs; Lo, Pechin Chien Pau; Dirksen, Asger

    2011-01-01

    A novel method for classification of abnormality in anatomical tree structures is presented. A tree is classified based on direct comparisons with other trees in a dissimilarity-based classification scheme. The pair-wise dissimilarity measure between two trees is based on a linear assignment...... by including anatomical features in the branch feature vectors. The proposed approach is applied to classify airway trees in computed tomography images of subjects with and without chronic obstructive pulmonary disease (COPD). Using the wall area percentage (WA%), a common measure of airway abnormality in COPD...

  5. Pulmonary Atresia

    Science.gov (United States)

    ... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocardial Bridge Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden ...

  6. Pregnancy in women with pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, P. G.; Hoendermis, E. S.

    2011-01-01

    Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced

  7. Pregnancy in women with pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, P. G.; Hoendermis, E. S.

    2011-01-01

    Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced

  8. Caution is recommended prior to sildenafil use in vascular anomalies.

    Science.gov (United States)

    Rankin, Hannah; Zwicker, Kelley; Trenor, Cameron C

    2015-11-01

    Since publication of a single case report of lymphatic malformation improvement during sildenafil therapy for pulmonary hypertension, sildenafil use has propagated across multiple vascular anomalies diagnoses. Vascular anomalies are rare conditions, often with poor long-term outcomes from available therapies, making these patients vulnerable to novel therapy use. We have retrospectively reviewed 14 children with vascular anomalies treated with sildenafil. None of these patients reported improvement of disease while on treatment and some reported side effects including infections and bleeding. Pending more convincing prospective data, we recommend caution prior to sildenafil use for vascular anomalies.

  9. Interpreting Tree Ensembles with inTrees

    OpenAIRE

    Deng, Houtao

    2014-01-01

    Tree ensembles such as random forests and boosted trees are accurate but difficult to understand, debug and deploy. In this work, we provide the inTrees (interpretable trees) framework that extracts, measures, prunes and selects rules from a tree ensemble, and calculates frequent variable interactions. An rule-based learner, referred to as the simplified tree ensemble learner (STEL), can also be formed and used for future prediction. The inTrees framework can applied to both classification an...

  10. Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options

    Directory of Open Access Journals (Sweden)

    I. M. Lang

    2009-03-01

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk. Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a "dual" pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension. Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met. More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.

  11. Pulmonary complications of transcatheter arterial chemoembolization for hepatocellular carcinoma

    Science.gov (United States)

    Nhu, Quan M; Knowles, Harry; Pockros, Paul J; Frenette, Catherine T

    2016-01-01

    Transarterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery. PMID:27904836

  12. [Novel immunopathological approaches to pulmonary arterial hypertension].

    Science.gov (United States)

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.

  13. Tree-space statistics and approximations for large-scale analysis of anatomical trees.

    Science.gov (United States)

    Feragen, Aasa; Owen, Megan; Petersen, Jens; Wille, Mathilde M W; Thomsen, Laura H; Dirksen, Asger; de Bruijne, Marleen

    2013-01-01

    Statistical analysis of anatomical trees is hard to perform due to differences in the topological structure of the trees. In this paper we define statistical properties of leaf-labeled anatomical trees with geometric edge attributes by considering the anatomical trees as points in the geometric space of leaf-labeled trees. This tree-space is a geodesic metric space where any two trees are connected by a unique shortest path, which corresponds to a tree deformation. However, tree-space is not a manifold, and the usual strategy of performing statistical analysis in a tangent space and projecting onto tree-space is not available. Using tree-space and its shortest paths, a variety of statistical properties, such as mean, principal component, hypothesis testing and linear discriminant analysis can be defined. For some of these properties it is still an open problem how to compute them; others (like the mean) can be computed, but efficient alternatives are helpful in speeding up algorithms that use means iteratively, like hypothesis testing. In this paper, we take advantage of a very large dataset (N = 8016) to obtain computable approximations, under the assumption that the data trees parametrize the relevant parts of tree-space well. Using the developed approximate statistics, we illustrate how the structure and geometry of airway trees vary across a population and show that airway trees with Chronic Obstructive Pulmonary Disease come from a different distribution in tree-space than healthy ones. Software is available from http://image.diku.dk/aasa/software.php.

  14. The relationship between atherosclerosis and pulmonary emphysema

    Directory of Open Access Journals (Sweden)

    Vučević Danijela

    2014-01-01

    Full Text Available Introduction. The etiopathogenesis of atherosclerosis and subsequent pulmonary emphysema has not been fully elucidated. Experimental Studies Foam cells are of great importance in the development of these diseases. It is known that local cytokine secretion and modification of native lipoprotein particles, which are internalized by the vascular and alveolar macrophages via the scavenger receptors on the surfaces of these cells, lead to the formation of foam cells. Thus, the exacerbation of local inflammatory process in the vascular and lung tissue ensues due to a generation of reactive oxygen species, resulting in further lipoprotein modification and cytokine production. Accumulating evidence suggests that oxidants may facilitate the inflammatory response by impairing antiprotease function, directly attacking vascular and lung matrix proteins and by inactivating enzymes involved in elastin synthesis and vascular and lung repair. Clinical Studies Cigarette smoke is recognized as a rich source of oxidants. Nearly 90% of all patients with chronic obstructive pulmonary disease are smokers. The process of atherogenesis is also influenced by tobacco smoke. Conclusion The role of vascular and alveolar macrophages has become increasingly important in understanding the development of atherosclerosis and resulting pulmonary emphysema.[Projekat Ministarstva nauke Republike Srbije, br. 175015

  15. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension

    OpenAIRE

    Monaco TJ; Davila CD

    2016-01-01

    Thomas J Monaco,1 Carlos D Davila2 1Division of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, 2Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA Abstract: Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary ar...

  16. Clinical characteristics and epidemiology of pulmonary pseudallescheriasis

    NARCIS (Netherlands)

    Kantarcioglu, A.S.; de Hoog, G.S.; Guarro, J.

    2012-01-01

    Background: Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections.

  17. Clinical characteristics and epidemiology of pulmonary pseudallescheriasis

    NARCIS (Netherlands)

    Kantarcioglu, A.S.; de Hoog, G.S.; Guarro, J.

    2012-01-01

    Background: Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections.

  18. Reactive oxygen species as therapeutic targets in pulmonary hypertension.

    Science.gov (United States)

    Freund-Michel, Véronique; Guibert, Christelle; Dubois, Mathilde; Courtois, Arnaud; Marthan, Roger; Savineau, Jean-Pierre; Muller, Bernard

    2013-06-01

    Pulmonary hypertension (PH) is characterized by a progressive elevation of pulmonary arterial pressure due to alterations of both pulmonary vascular structure and function. This disease is rare but life-threatening, leading to the development of right heart failure. Current PH treatments, designed to target altered pulmonary vascular reactivity, include vasodilating prostanoids, phosphodiesterase-5 inhibitors and endothelin-1 receptor antagonists. Although managing to slow the progression of the disease, these molecules still do not cure PH. More effective treatments need to be developed, and novel therapeutic strategies, targeting in particular vascular remodelling, are currently under investigation. Reactive oxygen species (ROS) are important physiological messengers in vascular cells. In addition to atherosclerosis and other systemic vascular diseases, emerging evidence also support a role of ROS in PH pathogenesis. ROS production is increased in animal models of PH, associated with NADPH oxidases increased expression, in particular of several Nox enzymes thought to be the major source of ROS in the pulmonary vasculature. These increases have also been observed in vitro and in vivo in humans. Moreover, several studies have shown either the deleterious effect of agents promoting ROS generation on pulmonary vasculature or, conversely, the beneficial effect of antioxidant agents in animal models of PH. In these studies, ROS production has been directly linked to pulmonary vascular remodelling, endothelial dysfunction, altered vasoconstrictive responses, inflammation and modifications of the extracellular matrix, all important features of PH pathophysiology. Altogether, these findings indicate that ROS are interesting therapeutic targets in PH. Blockade of ROS-dependent signalling pathways, or disruption of sources of ROS in the pulmonary vasculature, targeting in particular Nox enzymes, represent promising new therapeutic strategies in this disease.

  19. Comparison of zero-stress state of ascending aorta and pulmonary trunk between human and swine in vascular tissue reconstruction%血管组织重建中人与猪升主动脉、肺动脉干零应力状态的比较

    Institute of Scientific and Technical Information of China (English)

    余明华; 黄铁柱; 李文春; 王配军

    2006-01-01

    干各区段与猪肺动脉干近侧端(第1,2区段)的张开角相近.②不同月龄猪升主动脉、肺动脉干零应力状态张开角的测定结果比较:猪升主动脉、肺动脉干的张开角不随年龄增加而发生变化(P=0.063>0.05).结论:在某些区段人和猪升主动脉、肺动脉干的零应力状态张开角相近,提示猪→人异种心脏移植中相应升主动脉和肺动脉干在某些区段可以相互吻接,而且年龄因素在血管重建过程中的作用并不显著.%BACKGROUND: Due to the source of conspecific heart transplanted organ is limited and it becomes more and more deficient, and porcine cardiovascular system and haemodynamics are very similar to that of human being, therefore, domestic and foreign scholars have paid more attention on the heterogeneic heart transplantation from swine to human, and there are more and more basic studies about it.OBJECTIVE: To compare the zero-stress state of ascending aorta and pulmonary artery trunk between swine of different months and healthy persons, which provides necessary vascular tissue reconstruction basis for anastomosing vessel of heterogeneic heart transplantation from swine to human being.DESIGN: Open experiment.SETTING: Laboratory of Biomechanics, Yunyang Medical College.MATERIALS: This experiment was carried out at the Laboratory of Biomechanics, Yunyang Medical College from October 2001 to September 2002. Human heart specimens were chosen from 6 male adult corpses who had no visible manifestation of cardiovascular diseases, aged 18 to 30 years. Informed consents were obtained from all the relatives. Totally 42 conspecific swine, aged one month, were also chosen and divided into 7 groups, named as 1,2,3,4,5,6 and > 6 months groups respectively, with 6 in each group. Swine were anesthetized at 1,2,3,4,5,6,> 6 months respectively and sacrificed in each group.METHODS: The corresponding ascending aorta and pulmonary artery trunk were dissected and isolated. Each arterial anterior wall was

  20. Audubon Tree Study Program.

    Science.gov (United States)

    National Audubon Society, New York, NY.

    Included are an illustrated student reader, "The Story of Trees," a leaders' guide, and a large tree chart with 37 colored pictures. The student reader reviews several aspects of trees: a definition of a tree; where and how trees grow; flowers, pollination and seed production; how trees make their food; how to recognize trees; seasonal changes;…

  1. Kemampuan Cendawan Endofit dari KIon Kakao Tahan Penyakit Vascular Streak Dieback dalam Menekan Patogen Fusarium sp.

    OpenAIRE

    Asman; Nur, Amin; Tamrin, Abdullah

    2011-01-01

    Vascular Streak Dieback (VSD) is caused by Ceratobasidium theobromae and Ceratobasidium ramicola fungus, causes losses in seedling and young trees, kill branches in mature trees. It is a vascular pathogen difficult to growth on sintetic mediurn, because infects the vascular tissue, so that its control is difficult, the use of endophytic microorganism might be able to control this disease. Endophytic fungi is one of antagonist agent to control phytopathogen both bacterial or fungal. The resear...

  2. Interstitial Pulmonary Edema Following Bromocarbamide Intoxication

    Science.gov (United States)

    Sugihara, H.; Hagedorn, M.; Bōttcher, D.; Neuhof, H.; Mittermayer, Ch.

    1974-01-01

    Bromocarbamides are sleep-inducing drugs which can lead, in man, to intoxication and death due to respiratory failure. To prove whether hemodynamic factors or the changed endothelial permeability induce pulmonary edema, animal experiments were performed. The fine structural changes in pulmonary edema in rabbits were observed at 60, 90 and 120 minutes after oral administration. The major findings were a) large blebs between capillary endothelium and alveolar epithelium and b) interstitial edema of the vessel wall. The bleb contents were much less electron dense than the blood contents in the capillary. Colloidal carbon did not enter the bleb or the edematous interstitial tissue. Exogenous peroxidase uptake in pinocytotie vesicles increased in pathologic cases. The hemodynamic measurements in animal receiving artificial respiration which maintained the blood pO2 at a steady state showed similar blebs in the pulmonary vessels, indicating that anoxia is not the major cause of the vascular lesion. Moreover, pulmonary arterial pressure and pulmonary vascular resistance could be held in the normal range in artificially respirated animals under bromocarbamide intoxication. Thus, hemodynamic factors are not likely to play a pathogenetic role in bringing about pulmonary edema. The chief, early factor is the increased endothelial permeability due to increased cytoplasmic transport. From this a practical suggestion for treating patients with bromocarbamide intoxication is derived: the usual fluid replacement in shock patients should be handled with great care to avoid fluid overload of the lung. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4835993

  3. Current insights on the pathogenesis of pulmonary arterial hypertension.

    Science.gov (United States)

    Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc

    2005-08-01

    Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.

  4. Proximal pulmonary arterial obstruction decreases the time constant of the pulmonary circulation and increases right ventricular afterload.

    Science.gov (United States)

    Pagnamenta, Alberto; Vanderpool, Rebecca; Brimioulle, Serge; Naeije, Robert

    2013-06-01

    The time constant of the pulmonary circulation, or product of pulmonary vascular resistance (PVR) and compliance (Ca), called the RC-time, has been reported to remain constant over a wide range of pressures, etiologies of pulmonary hypertension, and treatments. We wondered if increased wave reflection on proximal pulmonary vascular obstruction, like in operable chronic thromboembolic pulmonary hypertension, might also decrease the RC-time and thereby increase pulse pressure and right ventricular afterload. Pulmonary hypertension of variable severity was induced either by proximal obstruction (pulmonary arterial ensnarement) or distal obstruction (microembolism) eight anesthetized dogs. Pulmonary arterial pressures (Ppa) were measured with high-fidelity micromanometer-tipped catheters, and pulmonary flow with transonic technology. Pulmonary ensnarement increased mean Ppa, PVR, and characteristic impedance, decreased Ca and the RC-time (from 0.46 ± 0.07 to 0.30 ± 0.03 s), and increased the oscillatory component of hydraulic load (Wosc/Wtot) from 25 ± 2 to 29 ± 2%. Pulmonary microembolism increased mean Ppa and PVR, with no significant change in Ca and characteristic impedance, increased RC-time from 0.53 ± 0.09 to 0.74 ± 0.05 s, and decreased Wosc/Wtot from 26 ± 2 to 13 ± 2%. Pulse pressure increased more after pulmonary ensnarement than after microembolism. Concomitant measurements with fluid-filled catheters showed the same functional differences between the two types of pulmonary hypertension, with, however, an underestimation of Wosc. We conclude that pulmonary hypertension caused by proximal vs. distal obstruction is associated with a decreased RC-time and increased pulsatile component of right ventricular hydraulic load.

  5. Vascular instruction of pancreas development.

    Science.gov (United States)

    Cleaver, Ondine; Dor, Yuval

    2012-08-01

    Blood vessels course through organs, providing them with essential nutrient and gaseous exchange. However, the vasculature has also been shown to provide non-nutritional signals that play key roles in the control of organ growth, morphogenesis and homeostasis. Here, we examine a decade of work on the contribution of vascular paracrine signals to developing tissues, with a focus on pancreatic β-cells. During the early stages of embryonic development, blood vessels are required for pancreas specification. Later, the vasculature constrains pancreas branching, differentiation and growth. During adult life, capillaries provide a vascular niche for the maintenance of β-cell function and survival. We explore the possibility that the vasculature constitutes a dynamic and regionalized signaling system that carries out multiple and changing functions as it coordinately grows with the pancreatic epithelial tree.

  6. Aspen Trees.

    Science.gov (United States)

    Canfield, Elaine

    2002-01-01

    Describes a fifth-grade art activity that offers a new approach to creating pictures of Aspen trees. Explains that the students learned about art concepts, such as line and balance, in this lesson. Discusses the process in detail for creating the pictures. (CMK)

  7. Clinical worsening after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B; Snijder, R; Morshuis, W; Saouti, N; Plokker, T; Post, M

    2011-12-01

    Pulmonary endarterectomy (PEA) is the most effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study is to evaluate long-term survival and freedom from clinical worsening after PEA. All patients who underwent PEA in our hospital between May 2000 and August 2009 were included. Follow-up parameters were all-cause mortality and time to clinical worsening, defined as a combination of death, need for pulmonary hypertension-specific medication or 15% decrease in six-minute walk distance without improvement in functional class. The Cox proportional hazard regression was used to identify predictors. Seventy-four consecutive patients (mean age 55.9 ± 13.8 years, 51% female) underwent PEA. Prior to surgery, 55 patients were in NYHA functional class III or higher. The mean pulmonary artery pressure was 41.3 ± 11.9 mmHg with a mean pulmonary vascular resistance of 521 ± 264 dyn·s·cm(-5) (range 279-1331 dyn·s·cm(-5)). Five patients (6.8%) died in-hospital. Out of hospital, 5 out of 69 patients (7.2%) died during a median follow-up of 3.7 ± 2.2 years [range 0.1-8.5 years]). The one- and five-year survival rates were 93% and 89%, respectively. During follow-up, clinical worsening occurred in 13 out of 69 patients (18.8%). The one- and five-year rates of freedom from clinical worsening were 94% and 72%, respectively. The baseline NT-pro BNP level tended to be a predictor for occurrence of clinical worsening. Pulmonary endarterectomy is associated with good long-term survival in patients with CTEPH. However, clinical worsening occurred in a substantial number of patients at long-term follow-up.

  8. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  9. Arterial pulmonary hypertension in noncardiac intensive care unit

    Directory of Open Access Journals (Sweden)

    Mykola V Tsapenko

    2008-10-01

    Full Text Available Mykola V Tsapenko1,5, Arseniy V Tsapenko2, Thomas BO Comfere3,5, Girish K Mour1,5, Sunil V Mankad4, Ognjen Gajic1,51Division of Pulmonary and Critical Care Medicine; 3Division of Critical Care Medicine; 4Division of Cardiovascular Diseases, Mayo Epidemiology and Translational Research in Intensive Care (M.E.T.R.I.C, Mayo Clinic, Rochester, MN, USA; 2Division of Pulmonary and Critical Care Medicine, Brown University, Miriam Hospital, Providence, RI, USAAbstract: Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in

  10. Pulmonary hypertension complicating pulmonary sarcoidosis

    NARCIS (Netherlands)

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should

  11. Pulmonary hypertension complicating pulmonary sarcoidosis

    NARCIS (Netherlands)

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    2016-01-01

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should

  12. Inflammation and pulmonary hypertension.

    Science.gov (United States)

    Mathew, Rajamma

    2010-01-01

    Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. Evidence is accumulating to suggest that inflammation plays a significant role in the pathogenesis of PH. Endothelial cells play an important role in inflammation and immune reactions, and inflammatory cytokines cause endothelial dysfunction. Endothelial dysfunction is a hallmark of PH, consisting of reduced availability of vasodilators and antiproliferative factors and increased production of vasoconstrictors and vascular proliferative factors. Up-regulation of inflammatory cytokines and perivascular inflammatory cell infiltration have been detected in the lungs of patients with idiopathic PH. Prevalence of PH in patients with systemic inflammatory diseases is well documented. Interestingly, a significant loss of endothelial caveolin-1, a potent immunomodulator and an inhibitor of cell proliferation, has been reported in human and experimental forms of PH. Reduction in the expression of caveolin-1 is known to result in the removal of antiproliferative activities, thus, leading to deregulated vascular cell proliferation. This article summarizes the roles of inflammation and endothelial caveolin-1 and their possible interrelationship in PH.

  13. Unimodular trees versus Einstein trees

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Enrique; Gonzalez-Martin, Sergio [Universidad Autonoma, Instituto de Fisica Teorica, IFT-UAM/CSIC, Madrid (Spain); Universidad Autonoma de Madrid, Departamento de Fisica Teorica, Madrid (Spain); Martin, Carmelo P. [Universidad Complutense de Madrid (UCM), Departamento de Fisica Teorica I Facultad de Ciencias Fisicas, Madrid (Spain)

    2016-10-15

    The maximally helicity violating tree-level scattering amplitudes involving three, four or five gravitons are worked out in Unimodular Gravity. They are found to coincide with the corresponding amplitudes in General Relativity. This a remarkable result, insofar as both the propagators and the vertices are quite different in the two theories. (orig.)

  14. Unimodular Trees versus Einstein Trees

    CERN Document Server

    Alvarez, Enrique; Martin, Carmelo P

    2016-01-01

    The maximally helicity violating (MHV) tree level scattering amplitudes involving three, four or five gravitons are worked out in Unimodular Gravity. They are found to coincide with the corresponding amplitudes in General Relativity. This a remarkable result, insofar as both the propagators and the vertices are quite different in both theories.

  15. Unimodular trees versus Einstein trees

    Science.gov (United States)

    Álvarez, Enrique; González-Martín, Sergio; Martín, Carmelo P.

    2016-10-01

    The maximally helicity violating tree-level scattering amplitudes involving three, four or five gravitons are worked out in Unimodular Gravity. They are found to coincide with the corresponding amplitudes in General Relativity. This a remarkable result, insofar as both the propagators and the vertices are quite different in the two theories.

  16. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease.

    Science.gov (United States)

    Montgomery, Gregory S; Sagel, Scott D; Taylor, Amy L; Abman, Steven H

    2006-04-01

    Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

  17. Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as Novel Therapeutic Targets

    Science.gov (United States)

    2015-10-01

    enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs). The underlying idea of this project is that the currently limited...Pulmonary arterial hypertension (PAH) is associated with increased vascular resistance, sustained contraction, and enhanced proliferation of pulmonary... CRISPR /Cas9) to knock down receptor expression in cells of interest and then to assess the impact of receptor knock down on functional activity

  18. Effects of platelet-derived growth factor on the function of smooth muscle cells from different orders of pulmonary artery

    Institute of Scientific and Technical Information of China (English)

    国桓

    2014-01-01

    Objective To explore the functional responses of normal rat pulmonary artery smooth muscle cells(PASMCs)from different orders of pulmonary artery to the platelet-derived growth factor(PDGF).Methods The pulmonary artery branches were gently isolated from Sprague-Dawley rats(250-350 g)and eventually cut into three groups according to the vascular grading:the

  19. Functional vascularized lung grafts for lung bioengineering

    Science.gov (United States)

    Dorrello, N. Valerio; Guenthart, Brandon A.; O’Neill, John D.; Kim, Jinho; Cunningham, Katherine; Chen, Ya-Wen; Biscotti, Mauer; Swayne, Theresa; Wobma, Holly M.; Huang, Sarah X. L.; Snoeck, Hans-Willem; Bacchetta, Matthew; Vunjak-Novakovic, Gordana

    2017-01-01

    End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell–derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation. PMID:28875163

  20. Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy: Is schistosomiasis hypertension an important confounding factor?

    Directory of Open Access Journals (Sweden)

    Mario Terra-Filho

    2010-01-01

    Full Text Available INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male. The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001. Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for

  1. Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy. Is schistosomiasis hypertension an important confounding factor?

    Science.gov (United States)

    Terra‐Filho, Mario; Mello, Marcos Figueiredo; Lapa, Mônica Silveira; Teixeira, Ricardo Henrique Oliveira Braga; Jatene, Fábio Biscegli

    2010-01-01

    INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty‐five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm‐5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p = 0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary

  2. Fruit load governs transpiration of olive trees.

    Science.gov (United States)

    Bustan, Amnon; Dag, Arnon; Yermiyahu, Uri; Erel, Ran; Presnov, Eugene; Agam, Nurit; Kool, Dilia; Iwema, Joost; Zipori, Isaac; Ben-Gal, Alon

    2016-03-01

    We tested the hypothesis that whole-tree water consumption of olives (Olea europaea L.) is fruit load-dependent and investigated the driving physiological mechanisms. Fruit load was manipulated in mature olives grown in weighing-drainage lysimeters. Fruit was thinned or entirely removed from trees at three separate stages of growth: early, mid and late in the season. Tree-scale transpiration, calculated from lysimeter water balance, was found to be a function of fruit load, canopy size and weather conditions. Fruit removal caused an immediate decline in water consumption, measured as whole-plant transpiration normalized to tree size, which persisted until the end of the season. The later the execution of fruit removal, the greater was the response. The amount of water transpired by a fruit-loaded tree was found to be roughly 30% greater than that of an equivalent low- or nonyielding tree. The tree-scale response to fruit was reflected in stem water potential but was not mirrored in leaf-scale physiological measurements of stomatal conductance or photosynthesis. Trees with low or no fruit load had higher vegetative growth rates. However, no significant difference was observed in the overall aboveground dry biomass among groups, when fruit was included. This case, where carbon sources and sinks were both not limiting, suggests that the role of fruit on water consumption involves signaling and alterations in hydraulic properties of vascular tissues and tree organs.

  3. H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension.

    Science.gov (United States)

    Feng, Shasha; Chen, Siyao; Yu, Wen; Zhang, Da; Zhang, Chunyu; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2017-03-01

    This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.

  4. Measurement of pulmonary flow reserve and pulmonary index of microcirculatory resistance for detection of pulmonary microvascular obstruction.

    Directory of Open Access Journals (Sweden)

    Rahn Ilsar

    Full Text Available BACKGROUND: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic/(basal flow] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressurex(maximum hyperemic T(mn]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. METHODS AND RESULTS: Temperature- and pressure-sensor guidewires (TPSG were placed in segmental pulmonary arteries (SPA of 13 baboons and intravascular temperature measured. T(mn and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min and papaverine (3-24 mg. Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1, supporting T(mn use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min & papaverine (to 24 mg induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn reductions v baseline, respectively; p<0.0001. PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4, 10(5 & 10(6 microspheres; p

  5. Management of blunt pulmonary injury.

    Science.gov (United States)

    Gallagher, John J

    2014-01-01

    Thoracic injuries account for 25% of all civilian deaths. Blunt force injuries are a subset of thoracic injuries and include injuries of the tracheobronchial tree, pleural space, and lung parenchyma. Early identification of these injuries during initial assessment and resuscitation is essential to reduce associated morbidity and mortality rates. Management of airway injuries includes definitive airway control with identification and repair of tracheobronchial injuries. Management of pneumothorax and hemothorax includes pleural space drainage and control of ongoing hemorrhage, along with monitoring for complications such as empyema and chylothorax. Injuries of the lung parenchyma, such as pulmonary contusion, may require support of oxygenation and ventilation through both conventional and nonconventional mechanical ventilation strategies. General strategies to improve pulmonary function and gas exchange include balanced fluid resuscitation to targeted volume-based resuscitation end points, positioning therapy, and pain management.

  6. Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Abdul Q. Sheikh

    2014-03-01

    Full Text Available Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.

  7. Vascular development in Arabidopsis.

    Science.gov (United States)

    Ye, Zheng-Hua; Freshour, Glenn; Hahn, Michael G; Burk, David H; Zhong, Ruiqin

    2002-01-01

    Vascular tissues, xylem and phloem, form a continuous network throughout the plant body for transport of water, minerals, and food. Characterization of Arabidopsis mutants defective in various aspects of vascular formation has demonstrated that Arabidopsis is an ideal system for investigating the molecular mechanisms controlling vascular development. The processes affected in these mutants include initiation or division of procambium or vascular cambium, formation of continuous vascular cell files, differentiation of procambium or vascular cambium into vascular tissues, cell elongation, patterned secondary wall thickening, and biosynthesis of secondary walls. Identification of the genes affected by some of these mutations has revealed essential roles in vascular development for a cytokinin receptor and several factors mediating auxin transport or signaling. Mutational studies have also identified a number of Arabidopsis mutants defective in leaf venation pattern or vascular tissue organization in stems. Genetic evidence suggests that the vascular tissue organization is regulated by the same positional information that determines organ polarity.

  8. Pulmonary Arterial Hypertension

    Science.gov (United States)

    Pulmonary Arterial Hypertension What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout your body. While the heart is one organ, it ...

  9. An Emerging Pulmonary Haemorrhagic Syndrome in Dogs: Similar to the Human Leptospiral Pulmonary Haemorrhagic Syndrome?

    Directory of Open Access Journals (Sweden)

    R. Klopfleisch

    2010-01-01

    Full Text Available Severe pulmonary haemorrhage is a rare necropsy finding in dogs but the leptospiral pulmonary haemorrhagic syndrome (LPHS is a well recognized disease in humans. Here we report a pulmonary haemorrhagic syndrome in dogs that closely resembles the human disease. All 15 dogs had massive, pulmonary haemorrhage affecting all lung lobes while haemorrhage in other organs was minimal. Histologically, pulmonary lesions were characterized by acute, alveolar haemorrhage without identifiable vascular lesions. Seven dogs had mild alveolar wall necrosis with hyaline membranes and minimal intraalveolar fibrin. In addition, eight dogs had acute renal tubular necrosis. Six dogs had a clinical diagnosis of leptospirosis based on renal and hepatic failure, positive microscopic agglutination test (MAT and/or positive blood/urine Leptospira-specific PCR. Leptospira could not be cultured post mortem from the lungs or kidneys. However, Leptospira-specific PCR was positive in lung, liver or kidneys of three dogs. In summary, a novel pulmonary haemorrhagic syndrome was identified in dogs but the mechanism of the massive pulmonary erythrocyte extravasation remains elusive. The lack of a consistent post mortem identification of Leptospira spp. in dogs with pulmonary haemorrhage raise questions as to whether additional factors besides Leptospira may cause this as yet unrecognized entity in dogs.

  10. The effects of oxygen induced pulmonary vasoconstriction on bedside measurement of pulmonary gas exchange.

    Science.gov (United States)

    Weinreich, Ulla M; Thomsen, Lars P; Rees, Stephen E; Rasmussen, Bodil S

    2016-04-01

    In patients with respiratory failure measurements of pulmonary gas exchange are of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary gas exchange is based on changes in inspired oxygen (FiO2) assuming that these changes do not affect pulmonary circulation. This assumption is investigated in this study. Forty-two out of 65 patients undergoing coronary artery bypass grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP), cardiac output and pulmonary capillary wedge pressure thus enabling the calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20 and ultimately returned towards baseline values, allowing 6-8 min' steady state period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2 reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of 4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately reversed on returning FiO2 towards baseline. In this study changes in MPAP and PVR are small and immediately reversible consistent with small changes in pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary vasoconstriction does not have significant influences on the ALPE parameters in patients after CABG.

  11. Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension.

    Science.gov (United States)

    Hetzel, M; Kochs, M; Marx, N; Woehrle, H; Mobarak, I; Hombach, V; Hetzel, J

    2003-01-01

    The association between nocturnal apneas and transient pulmonary hypertension (PHT) has been well documented. However, there is controversy over the frequency and pathophysiological mechanisms of daytime pulmonary hypertension in patients with obstructive sleep apnea (OSAS). The present study sought to evaluate frequency and mechanisms of pulmonary hypertension in patients with OSAS. It included 49 consecutive patients with polysomnographically proven OSAS without pathological lung function testing. All patients performed daytime measurements of pulmonary hemodynamics at rest and during exercise (50-75W). Six patients (12%) had resting PHT mean pulmonary of artery pressure (PAPM) of >20 mmHg), whereas 39 patients (80%) showed PHT during exercise (PAPM >30 mmHg). Multiple regression analysis revealed 3 independent contributing factors for mean pulmonary artery pressure during exercise (PAPMmax): body mass index, age and total lung capacity % of predicted. Twenty-five of the 39 patients with pathologically high PAPMmax (64%) showed elevated pulmonary capillary wedge pressures (PCWPmax > 20 mmHg), whereas no patient had elevated pulmonary vascular resistance (PVRmax > 120 dynes x s x cm(-5)). In conclusion, daytime PHT during exercise is frequently seen in patients with OSAS and normal lung function testing and is mainly caused by abnormally high PCWP, whereas PVR seems to play a minor role.

  12. Sarcoidosis with Major Airway, Vascular and Nerve Compromise

    Directory of Open Access Journals (Sweden)

    Hiroshi Sekiguchi

    2013-01-01

    Full Text Available The present report describes a 60-year-old Caucasian woman who presented with progressive dyspnea, cough and wheeze. A computed tomography scan of the chest showed innumerable bilateral inflammatory pulmonary nodules with bronchovascular distribution and a mediastinal and hilar infiltrative process with calcified lymphadenopathy leading to narrowing of lobar bronchi and pulmonary arteries. An echocardiogram revealed pulmonary hypertension. Bronchoscopy showed left vocal cord paralysis and significant narrowing of the bilateral bronchi with mucosal thickening and multiple nodules. Transbronchial biopsy was compatible with sarcoidosis. Despite balloon angioplasty of the left lower lobe and pulmonary artery, and medical therapy with oral corticosteroids, her symptoms did not significantly improve. To the authors’ knowledge, the present report describes the first case of pulmonary sarcoidosis resulting in major airway, vascular and nerve compromise due to compressive lymphadenopathy and suspected concurrent granulomatous infiltration. Its presentation mimicked idiopathic mediastinal fibrosis.

  13. Secuestro pulmonar Pulmonary sequestration

    Directory of Open Access Journals (Sweden)

    José Antonio Hernández Varea

    2010-06-01

    Full Text Available El secuestro pulmonar es una afección congénita que consiste en la presencia de una masa quística de tejido pulmonar afuncional que puede carecer de una obvia comunicación con el árbol traqueobronquial y recibe toda o la mayor parte de su irrigación sanguínea de vasos anómalos provenientes de la circulación sistémica. Teniendo en cuenta que la presentación de esta afección resulta rara comparada con otras afecciones pulmonares (entre 1 y 2 % de todas las resecciones pulmonares y que además lo más frecuente resulta su tratamiento definitivo antes de la edad adulta, se presenta el caso de un hombre de 44 años que acudió a consulta por presentar episodios frecuentes de neumonías desde hacía más de 10 años, que fueron diagnosticados como «bronquiectasias». Se discuten los hechos más significativos del origen embriológico de esta afección, características anatomopatológicas, clasificación, diagnóstico imaginológico, detalles del tratamiento quirúrgico y evolución posoperatoria.Pulmonary sequestration is a congenital affection consisting in the presence of a cystic mass of no-functional pulmonary tissue without an obvious communication with tracheobronchial tree and that receives all or most of its bloodstream of the anomalous vessels from systemic circulation. Taking into account that presentation of this affection is rare compared to other pulmonary affections (between the 1% and the 2% of all pulmonary resections and that also the more usual is its definitive treatment before adulthood. The case of man aged 44 is presented coming to consultation due to frequent episodes of pneumonias from more 10 years ago diagnosed as a bronchiectasis. The more significant facts of embryology origin of this affection including: anatomical and pathological features, imaging diagnosis, surgical treatment details, and postoperative course.

  14. [From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: Pathobiology and pathophysiology].

    Science.gov (United States)

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    Chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subtype of pulmonary hypertension characterized by the presence of mechanical obstruction of the major pulmonary vessels caused by venous thromboembolism. CTEPH is a progressive and devastating disease if not treated, and is the only subset of PH potentially curable by a surgical procedure known as pulmonary endarterectomy. The clot burden and pulmonary embolism recurrence may contribute to the development of CTEPH however only few thrombophilic factors have been found to be associated. A current hypothesis is that CTEPH results from the incomplete resolution and organization of thrombus modified by inflammatory, immunologic and genetic mechanisms, leading to the development of fibrotic stenosis and adaptive vascular remodeling of resistance vessels. The causes of thrombus non-resolution have yet to be fully clarified. CTEPH patients often display severe PH that cannot be fully explained by the degree of pulmonary vascular obstruction apparent on imaging studies. In such cases, the small vessel disease and distal obstructive thrombotic lesions beyond the sub-segmental level may contribute for out of proportion elevated PVR. The processes implicated in the development of arteriopathy and micro-vascular changes might explain the progressive nature of PH and gradual clinical deterioration with poor prognosis, as well as lack of correlation between measurable hemodynamic parameters and vascular obstruction even in the absence of recurrent venous thromboembolism. This review summarizes the most relevant up-to-date aspects on pathobiology and pathophysiology of CTEPH. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. How Is Pulmonary Hypertension Treated?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Treated? Pulmonary hypertension (PH) has no cure. However, ... Types of Pulmonary Hypertension." ) Group 1 Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension (PAH) includes PH ...

  16. Simple pulmonary eosinophilia

    Science.gov (United States)

    Pulmonary infiltrates with eosinophilia; Loffler syndrome; Eosinophilic pneumonia; Pneumonia - eosinophilic ... A rare complication of simple pulmonary eosinophilia is a severe type of pneumonia called acute idiopathic eosinophilic pneumonia.

  17. Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Adriana M Zimnicka

    Full Text Available Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX, a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2 also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC. In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness.

  18. Finite Sholander Trees, Trees, and their Betweenness

    CERN Document Server

    Chvátal, Vašek; Schäfer, Philipp Matthias

    2011-01-01

    We provide a proof of Sholander's claim (Trees, lattices, order, and betweenness, Proc. Amer. Math. Soc. 3, 369-381 (1952)) concerning the representability of collections of so-called segments by trees, which yields a characterization of the interval function of a tree. Furthermore, we streamline Burigana's characterization (Tree representations of betweenness relations defined by intersection and inclusion, Mathematics and Social Sciences 185, 5-36 (2009)) of tree betweenness and provide a relatively short proof.

  19. [Pulmonary hypertension in pediatric heart surgery].

    Science.gov (United States)

    Falcone, N

    2001-12-01

    Congenital heart disease can increase or decrease pulmonary blood flow, pulmonary vascular resistance (PVR) or pulmonary artery pressure (PAP). PAP is the product of PVR and pulmonary minute volume (Qp), such that pulmonary hypertension (PHT) may develop as a result of an increase in either PVR or Qp or both. Given that the pulmonary vascular bed is a low pressure system with high flow, any increase in resistance would generate PHT. The normal value of PVR is 2 Woods units (mm Hg/l/min). Increased PAP is due to hypoxic lesions of the endothelium, which release proteolytic enzymes that alter the balance of metabolites of arachidonic acid, regulators of pulmonary vasomotor tone. Hypoxia and acidosis cause intense pulmonary vasoconstriction (hypoxic vasoconstrictor reflex). An increase of PVR is due to a combination of vasoconstrictive processes and remodeling, with hypertrophy of the pulmonary artery. Structural lesions are related to hypertrophy of the endothelium, the transformation of fibroblasts to myocytes and the decrease of the alveolar/arteriolar ratio with the formation of new vessels.PHT may be primary or secondary to another disease. Primary PHT is a rare genetic disease. The most common secondary forms of PHT in pediatrics are due to persistence of neonatal anatomy (neonatal PHT), to heart diseases with left-right shunt (CIV, DAP, etc.), to diseases of the pulmonary parenchyma (interstitial viral infection, mucoviscidosis), and complications of heart surgery. All congenital heart diseases can lead to PHT if not treated promptly. Clinical signs of PHT are highly non-specific: dyspnea, fatigue, syncopes, exercise intolerance, precordialgia, cyanosis and edema. The best approaches to diagnosis and prognosis are echocardiography and cardiac catheterization with vasodilators. Anesthetics that do not alter PVR should be used in such patients, who are sensitive to changes in pulmonary ventilation, to changes in cardiac output and to anesthetics. The treatment of

  20. [Pulmonary strongyloidiasis].

    Science.gov (United States)

    Lozada, Heiler; Daza, Jorge E

    2016-10-01

    Strongyloidiasis is an infection caused by the parasite Strongyloides stercoralis, which can be asymptomatic and means a high morbidity and mortality in immunocompromised hosts, severe malnutrition and coinfection with HTLV-1 virus. The parasite has the potential to produce and multiply internal autoinfection in humans, thus an hyperinfection can be developed. A case of pulmonary infection by this parasite is presented in this study, infection which advanced into a respiratory failure and required mechanical ventilation and hemodynamic support in an intensive care unit. The standard treatment combined with ivermectin and albendazole was provided, achieving an appropriate response.

  1. Pathogenic Mechanisms of Pulmonary Arterial Hypertension

    Science.gov (United States)

    Chan, Stephen Y.; Loscalzo, Joseph

    2008-01-01

    Pulmonary arterial hypertension (PAH)1 is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease. PMID:17950310

  2. Branding of vascular surgery.

    Science.gov (United States)

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  3. Diagnostic Evaluation of Chronic Thromboembolic Pulmonary Hypertension.

    Science.gov (United States)

    Gopalan, Deepa; Blanchard, Daniel; Auger, William R

    2016-07-01

    Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 25 mm Hg. Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as pulmonary hypertension in the presence of an organized thrombus within the pulmonary vascular bed that persists at least 3 months after the onset of anticoagulant therapy. Because CTEPH is potentially curable by surgical endarterectomy, correct identification of patients with this form of pulmonary hypertension and an accurate assessment of surgical candidacy are essential to provide optimal care. Patients most commonly present with symptoms of exertional dyspnea and otherwise unexplained decline in exercise capacity. Atypical chest pain, a nonproductive cough, and episodic hemoptysis are observed less frequently. With more advanced disease, patients often develop symptoms suggestive of right ventricular compromise. Physical examination findings are minimal early in the course of this disease, but as pulmonary hypertension progresses, may include nonspecific finding of right ventricular failure, such as a tricuspid regurgitation murmur, pedal edema, and jugular venous distention. Chest radiographs may suggest pulmonary hypertension, but are neither sensitive nor specific for the diagnosis. Radioisotopic ventilation-perfusion scanning is sensitive for detecting CTEPH, making it a valuable screening study. Conventional catheter-based pulmonary angiography retains an important role in establishing the presence and extent of chronic thromboembolic disease. However, computed tomographic and magnetic resonance imaging are playing a growing diagnostic role. Innovative technologies such as dual-energy computed tomography, dynamic contrast-enhanced magnetic resonance imaging, and optical coherence tomography show promise for contributing diagnostic information and assisting in the preoperative characterization of patients with CTEPH.

  4. 慢性阻塞性肺疾病患者颅内血管的CT表现%CT Manifestation of Intracranial Vascular in Chronic Obstructive Pulmonary Disease Patients

    Institute of Scientific and Technical Information of China (English)

    丁永正

    2013-01-01

    目的:探讨CT对COPD患者颅内血管改变的诊断意义。方法:采用MSCT行脑CTP检查,对生成的CBF、CBV、MTT3种参数与对照组进行对比;并行脑CTA检查,观察脑内大血管分支狭窄及闭塞情况,并分析该情况的高发部位。结果:在研究中我们发现,Ⅲ级、Ⅳ级COPD患者CBF、CBV、MTT3种参数与正常组相比,有明显差异(P<0.05);脑CTA检查发现随着COPD程度的加重,颅内动脉狭窄发生率越高,并好发于大脑中动脉、颈内动脉、大脑后动脉、基底动脉、大脑前动脉。结论:目的:探讨CT对COPD患者颅内血管改变的诊断意义。方法:采用MSCT行脑CTP检查,对生成的CBF、CBV、MTT3种参数与对照组进行对比;并行脑CTA检查,观察脑内大血管分支狭窄及闭塞情况,并分析该情况的高发部位。结果:在研究中我们发现,Ⅲ级、Ⅳ级COPD患者CBF、CBV、MTT3种参数与正常组相比,有明显差异(P<0.05);脑CTA检查发现随着COPD程度的加重,颅内动脉狭窄发生率越高,并好发于大脑中动脉、颈内动脉、大脑后动脉、基底动脉、大脑前动脉。结论:COPD患者可合并颅内血管及血液灌注的改变,CT检查能够早期快速、准确反映颅内血管病变的程度及部位,对该病的预防和治疗有重要意义。%Objective:Approached the meaning of CT diagnosis in COPD patients with intracranial vascular changes .Methods:Checked the brain CTP in MSCT ,Generated three parameters ( CBF,CBV,MTT) ,and compared with the control group;And checked the brain CTA,observed the information of stenosis and occlusion in brain vascular branch ,and analyzed the the high incidence parts .Re-sults:In the study, we found that compared with the normal group ,Ⅲand IV grade COPD patients had significant difference (P <0.05) in CBF, CBV, MTT three parameters;we also found that the more serious in COPD , the higher incident in the

  5. Office-based vascular lab: is it worth the effort?

    Science.gov (United States)

    Mansour, M Ashraf; Zwolak, Robert M

    2009-03-01

    The vascular laboratory is an essential part of any contemporary clinical vascular practice. The prototype of the vascular laboratory consisted mainly of instruments designed to understand the hemodynamics of the vascular tree. Earlier versions also played important roles in clinical research. Currently, sophisticated imaging equipments enable clinicians to evaluate the whole range of arterial and venous diseases in the outpatient setting. Both patients and physicians have found this to be very practical and convenient. Furthermore, income generated from performing diagnostic tests in the vascular laboratory helps support a variety of clinical activities and research. However, recent cost-cutting measures by medical insurance carriers are threatening the viability of office-based vascular laboratories

  6. Clinical and radiological evolution in patients with pulmonary Langerhans' cell histiocytosis

    NARCIS (Netherlands)

    Westerlaan, HE; van der Valk, PDLPM

    2002-01-01

    Background: Pulmonary Langerhans' cell histiocytosis (LCH) is a diffuse, smoking-related lung disease characterised pathologically by proliferation of abnormal Langerhans' cells, cyst formation and vascular abnormalities, and physiologically by a decreased diffusing capacity. The aim of this study w

  7. [Idiopathic pulmonary hemosiderosis with dendriform pulmonary ossification].

    Science.gov (United States)

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

    Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.

  8. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina

    2006-01-01

    There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current l

  9. Pulmonary chondroid hamartoma with nontuberculous mycobacterial infection: two case reports.

    Science.gov (United States)

    Lee, Yong Chul; Moon, Jin Chang; Gang, Su Jin; Park, Seung Yong; Kim, So Ri

    2015-04-01

    Solitary pulmonary nodules (SPNs) can be manifested in a variety of disorders including neoplasms, infection, inflammation, and vascular or congenital abnormalities. In addition, they are often accompanied with other pulmonary pathologic lesions such as consolidations and several pulmonary disorders present as similar pulmonary nodular lesions simultaneously. Diagnostic workup is important for these SPNs; however, many physicians often miss the second diagnosis for multiple pulmonary lesions with SPNs due to lack of clinical suspicion that each pulmonary nodule or pathologic lesion can have each other's diagnosis. Herein, we report 2 cases of coexistence of pulmonary chondroid hamartoma with nontuberculous mycobacterial (NTM) infection presenting as pulmonary nodules and multiple consolidative lesions. A 60-year-old man was admitted for the evaluation of multifocal pulmonary lesions including SPN with chronic exertional dyspnea. Multiple lung tissues were obtained from each lesion through percutaneous transthoracic needle biopsy (PTNB). At the same time, bacteriologic examination was performed using respiratory samples obtained by bronchoscopy. Based on pathologic and microbiologic results, the patient diagnosed as pulmonary chondroid hamartoma with pulmonary NTM infectious disease. In addition, a 56-year-old woman visited for the evaluation of a small SPN. The SPN was resected surgically for the pathologic examination and turned out to be pulmonary chondroid hamartoma. Interestingly, the diagnostic workup revealed that the patient had Lady Windermere syndrome which is one of features for Mycobacterium avium complex (MAC) pulmonary disease. Both patients were treated with the standard antibiotics against MAC as recommended by the ATS/IDSA guideline. This is the first report of 2 patients, as far as we know, that chondroid hamartoma and NTM disease develop simultaneously in the lung. This report emphasizes that physicians should endeavor to confirm the individual

  10. Smooth muscle myosin inhibition: a novel therapeutic approach for pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    David Ho

    Full Text Available OBJECTIVE: Pulmonary hypertension remains a major clinical problem despite current therapies. In this study, we examine for the first time a novel pharmacological target, smooth muscle myosin, and determine if the smooth muscle myosin inhibitor, CK-2019165 (CK-165 ameliorates pulmonary hypertension. MATERIALS AND METHODS: Six domestic female pigs were surgically instrumented to measure pulmonary blood flow and systemic and pulmonary vascular dynamics. Pulmonary hypertension was induced by hypoxia, or infusion of the thromboxane analog (U-46619, 0.1 µg/kg/min, i.v.. In rats, chronic pulmonary hypertension was induced by monocrotaline. RESULTS: CK-165 (4 mg/kg, i.v. reduced pulmonary vascular resistance by 22±3 and 28±6% from baseline in hypoxia and thromboxane pig models, respectively (p<0.01 and 0.01, while mean arterial pressure also fell and heart rate rose slightly. When CK-165 was delivered via inhalation in the hypoxia model, pulmonary vascular resistance fell by 17±6% (p<0.05 while mean arterial pressure and heart rate were unchanged. In the monocrotaline model of chronic pulmonary hypertension, inhaled CK-165 resulted in a similar (18.0±3.8% reduction in right ventricular systolic pressure as compared with sildenafil (20.3±4.5%. CONCLUSION: Inhibition of smooth muscle myosin may be a novel therapeutic target for treatment of pulmonary hypertension.

  11. Modular Tree Automata

    DEFF Research Database (Denmark)

    Bahr, Patrick

    2012-01-01

    Tree automata are traditionally used to study properties of tree languages and tree transformations. In this paper, we consider tree automata as the basis for modular and extensible recursion schemes. We show, using well-known techniques, how to derive from standard tree automata highly modular r...

  12. Simple street tree sampling

    Science.gov (United States)

    David J. Nowak; Jeffrey T. Walton; James Baldwin; Jerry. Bond

    2015-01-01

    Information on street trees is critical for management of this important resource. Sampling of street tree populations provides an efficient means to obtain street tree population information. Long-term repeat measures of street tree samples supply additional information on street tree changes and can be used to report damages from catastrophic events. Analyses of...

  13. Modular tree automata

    DEFF Research Database (Denmark)

    Bahr, Patrick

    2012-01-01

    Tree automata are traditionally used to study properties of tree languages and tree transformations. In this paper, we consider tree automata as the basis for modular and extensible recursion schemes. We show, using well-known techniques, how to derive from standard tree automata highly modular...

  14. Mycotic pulmonary artery aneurysm as an unusual complication of thoracic actinomycosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung-Soo; Lee, Sang-Yeub [Wonkwang University College, Iksan (Korea, Republic of); Oh, Yu-Whan; Noh, Hyung-Jun; Lee, Ki-Yeol; Kang, Eun-Young [Korea University Hospital and Korea University College, Seoul (Korea, Republic of)

    2004-03-15

    Although pulmonary artery aneurysms are a rare vascular anomaly, they are seen in a wide variety of conditions, such as congenital heart disease, infection, trauma, pulmonary hypertension, cystic medial necrosis and generalized vasculitis. To our knowledge, mycotic aneurysms caused by pulmonary actinomycosis have not been reported in the radiologic literature. Herein, a case of pulmonary actinomycosis complicated by mycotic aneurysm is presented. On CT scans, this case showed focal aneurysmal dilatation of a peripheral pulmonary artery within necrotizing pneumonia of the right lower lobe, which was successfully treated with transcatheter embolization using wire coils.

  15. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

    DEFF Research Database (Denmark)

    Su, Junjing; Hilberg, Ole; Howard, Luke

    2016-01-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects...... reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used...

  16. Common and uncommon vascular rings and slings: a multi-modality review

    Energy Technology Data Exchange (ETDEWEB)

    Dillman, Jonathan R.; Agarwal, Prachi P.; Hernandez, Ramiro J.; Strouse, Peter J. [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Attili, Anil K. [University of Kentucky College of Medicine, Department of Radiology, Lexington, KY (United States); Dorfman, Adam L. [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States)

    2011-11-15

    Vascular rings and pulmonary slings are congenital anomalies of the aortic arch/great vessels and pulmonary arteries, respectively, that commonly present early during infancy and childhood with respiratory and/or feeding difficulties. The diagnosis of these conditions frequently utilizes a multi-modality radiological approach, commonly utilizing some combination of radiography, esophagography, CT angiography and MR angiography. The purpose of this pictorial review is to illustrate the radiological findings of common and uncommon vascular rings and pulmonary slings in children using a state-of-the-art multi-modality imaging approach. (orig.)

  17. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

    OpenAIRE

    XU, DUNQUAN; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The pres...

  18. Toxicological effects of beryllium on platelets and vascular endothelium.

    Science.gov (United States)

    Togna, G; Togna, A R; Russo, P; Caprino, L

    1997-06-01

    Although ample research has described the toxic effects of the metal beryllium on the respiratory apparatus, less is known about its effects on the vascular apparatus, including pulmonary blood vessels. We investigated the in vitro effects of beryllium on endothelial vascular adenosine diphosphatase activity and prostacyclin production in bovine aortic endothelium, and on nitric oxide release in isolated rabbit arteries. Rabbit and human platelet responsiveness was also evaluated. Beryllium inhibited vascular endothelial adenosine diphosphatase activity, prostacyclin production, and nitric oxide release, thus inducing functional alterations in vascular endothelial cells. It also induced platelet hyperreactivity to arachidonic acid, as shown by a lowering of the threshold of aggregating concentration and by concurrently increasing thromboxane production. In contrast, beryllium left the response to aggregating and nonaggregating concentrations of ADP and collagen unchanged. These findings show that beryllium may impair some vascular endothelial functions and alter the interaction between platelet and endothelial mediators.

  19. Postoperative management of pulmonary endarterectomy and outcome

    Directory of Open Access Journals (Sweden)

    Narayana Iyengar Ramakrishna

    2010-01-01

    Full Text Available Pulmonary artery thromboendarterectomy (PTE has been regarded as a promising, potentially curative surgical procedure. However, PTE is associated with specific postoperative complications, such as reperfusion pulmonary edema and right heart failure leading to a considerable mortality of 7-24%. Despite its limitations PTE is a better surgical alternative to lung transplantation which carries high morbidity and mortality. The aim of the study is to analyze the efficacy, safety, morbidity and survival associated in the postoperative period and quality of life after six months of PTE in Indian patients. Forty-one patients with surgically correctable chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy. All patients were in New York Heart Association (NYHA Class II, III or IV. Preoperative mean pulmonary artery pressure was 40.98 ± 9.29 mmHg and mean pulmonary vascular resistance was 418.39 ± 95.88 dynes/sec/cm -5 . All patients were followed up to six months and a telephonic survey was conducted using a standard questionnaire. They were assessed and classified as per NYHA grading. There was a significant reduction in the mean pulmonary artery pressure (from 40.98 ± 9.29 mmHg to 24.13 ± 7.36 mmHg, P < 0.001 and pulmonary vascular resistance (from 418.39 ± 95.88 dynes/sec/cm -5 to 142.45 ± 36.27 dynes/sec/cm -5 , P < 0.001 with a concomitant increase in the cardiac index (from 1.99 ± 0.20 L/min/m 2 to 3.28 ± 0.56 L/min/m 2 , P < 0.001 during the postoperative period. The mortality rate in our study was 12.19% (five patients. Ninety per cent of the patients reported a significant improvement in the quality of life and exercise tolerance after surgery compared to the preoperative state. Pulmonary endarterectomy is an effective and potentially curative surgical treatment for patients with severe chronic thromboembolic pulmonary hypertension. The current techniques of operation make the procedure relatively safe and

  20. Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    MacKenzie Ross, Robert V; Toshner, Mark R; Soon, Elaine; Naeije, Robert; Pepke-Zaba, Joanna

    2013-07-15

    This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance (Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned that increased wave reflection in proximal CTEPH would be another cause of the decreased RC time constant. We conducted a retrospective analysis of invasive pulmonary hemodynamic measurements in IPAH (n = 78), proximal CTEPH (n = 91) before (pre) and after (post) pulmonary endarterectomy (PEA), and distal CTEPH (n = 53). Proximal CTEPH was defined by a postoperative mean pulmonary artery pressure (PAP) of ≤25 mmHg. Outcome measures were the RC time constant, PVR, Ca, and relationship between systolic and mean PAPs. The RC time constant for pre-PEA CTEPH was 0.49 ± 0.11 s compared with post-PEA-CTEPH (0.37 ± 0.11 s, P time constant was associated with a disproportionate decrease in systolic PAP with respect to mean PAP. We concluded that the pulmonary RC time constant is decreased in proximal CTEPH compared with IPAH, pre- and post-PEA, which may be explained by increased wave reflection but also, importantly, by persistent structural changes after the removal of proximal obstructions. A reduced RC time constant in CTEPH is in accord with a wider pulse pressure and hence greater right ventricular work for a given mean PAP.

  1. [Thrombo-embolic pulmonary hypertension--do not spoil a chance for effective surgery!].

    Science.gov (United States)

    Kurzyna, Marcin; Torbicki, Adam; Poloński, Lech; Skoczylas, Ilona; Przybylski, Roman; Wieteska, Maria; Dyk, Wojciech; Biederman, Andrzej; Zembala, Marian

    2011-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension with persistent pulmonary perfusion defects causes by unresolved thrombi. All symptomatic CTEPH patients with documented pulmonary vascular resistance > 300 dyn*sec*cm(-5) and proximal lesions should be considered for surgical treatment--pulmonary endarterectomy. The role of pharmacological treatment remains controversial and should be restricted to inoperable cases and persistent pulmonary hypertension after pulmonary endarterectomy. Every year about 30 procedures is performed in two specialised centers in Poland with 1 year mortality at 8-9%. Number of procedures done gives the frequency of pulmonary endarterectomy at 0.7/million of population/year. Current data from UK indicate the actual ratio of surgical treatment of CTPH at 2/million/year. The article discusses reasons for CTEPH is underdiagnosed and why rate of surgical therapy in Poland is too low.

  2. Multinephron dynamics on the renal vascular network

    DEFF Research Database (Denmark)

    Marsh, Donald J; Wexler, Anthony S; Brazhe, Alexey

    2012-01-01

    ensemble. Ensembles may synchronize. Smooth muscle cells in the ensemble depolarize periodically, generating electrical signals that propagate along the vascular network. We developed a mathematical model of a nephron-vascular network, with 16 versions of a single nephron model containing representations...... of both mechanisms in the regulatory ensemble, to examine the effects of network structure on nephron synchronization. Symmetry, as a property of a network, facilitates synchronization. Nephrons received blood from a symmetric electrically conductive vascular tree. Symmetry was created by using identical...... nephron models at each of the 16 sites, and symmetry breaking by varying nephron length. The symmetric model achieved synchronization of all elements in the network. As little as 1% variation in nephron length caused extensive desynchronization, although synchronization was maintained in small nephron...

  3. tion of vascular malformations

    African Journals Online (AJOL)

    classification of vascular anomalies outside of the central ... The current classification of CNS vascular ... tural proteins within the wall of caver- .... ing (or established) loss of function or a threat to ..... natural history of the strawberry nevus. Arch.

  4. Society for Vascular Medicine

    Science.gov (United States)

    ... Certification with this new online course from the Society for Vascular Medicine. Learn more. Looking for a ... jobs are listed right now. Copyright © 2016 The Society for Vascular Medicine. All Rights Reserved.

  5. Collagen vascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific ...

  6. Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Froelich, Jens J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: jens.froelich@klinikum-hef.de; Koenig, Helmut [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: helmut.koenig@siemens.com; Knaak, Lennard [Department of Medicine, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: froehlic@staff.uni-marburg.de; Krass, Stefan [MeVis Research, Universitaetsallee 29, 28359 Bremen (Germany)], E-mail: krass@mevis.de; Klose, Klaus J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: klose@med.uni-marburg.de

    2008-09-15

    Objectives: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. Materials and methods: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3 mm; pitch 2; increment 2 mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. Results: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r = .85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p < .005), PA volumes also were significantly increased (p < .05) among the groups. Conclusions: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension.

  7. Effect of Injecting Hydrogen Peroxide into Heavy Clay Loam Soil on Plant Water Status, NET CO2 Assimilation, Biomass, and Vascular Anatomy of Avocado Trees Efecto de la Inyección de Peróxido de Hidrógeno en Suelo Franco Arcilloso Pesado, sobre el Estado Hídrico, Asimilación Neta de CO2, Biomasa y Anatomía Vascular de Paltos

    Directory of Open Access Journals (Sweden)

    Pilar M Gil M

    2009-03-01

    Full Text Available In Chile, avocado (Persea americana Mill. orchards are often located in poorly drained, low-oxygen soils, situation which limits fruit production and quality. The objective of this study was to evaluate the effect of injecting soil with hydrogen peroxide (H2O2 as a source of molecular oxygen, on plant water status, net CO2 assimilation, biomass and anatomy of avocado trees set in clay loam soil with water content maintained at field capacity. Three-year-old ‘Hass’ avocado trees were planted outdoors in containers filled with heavy loam clay soil with moisture content sustained at field capacity. Plants were divided into two treatments, (a H2O2 injected into the soil through subsurface drip irrigation and (b soil with no H2O2 added (control. Stem and root vascular anatomical characteristics were determined for plants in each treatment in addition to physical soil characteristics, net CO2 assimilation (A, transpiration (T, stomatal conductance (gs, stem water potential (SWP, shoot and root biomass, water use efficiency (plant biomass per water applied [WUEb]. Injecting H2O2 into the soil significantly increased the biomass of the aerial portions of the plant and WUEb, but had no significant effect on measured A, T, gs, or SWP. Xylem vessel diameter and xylem/phloem ratio tended to be greater for trees in soil injected with H2O2 than for controls. The increased biomass of the aerial portions of plants in treated soil indicates that injecting H2O2 into heavy loam clay soils may be a useful management tool in poorly aerated soil.En Chile, los huertos de palto (Persea americana Mill. se ubican comúnmente en suelos pobremente drenados con bajo contenido de oxígeno, lo que limita producción y calidad de fruta. El objetivo de este estudio fue evaluar el efecto de la inyección de peróxido de hidrógeno (H2O2 al suelo como fuente de O2, sobre el estado hídrico, asimilación de CO2, biomasa y anatomía de paltos en suelo franco arcilloso con

  8. Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

    2008-05-15

    Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

  9. Apelin and pulmonary hypertension

    DEFF Research Database (Denmark)

    Andersen, Charlotte Uggerhøj; Hilberg, Ole; Mellemkjær, Søren;

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin...... vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting...

  10. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt;

    2000-01-01

    was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...... patients (P analysis showed that vascular grading contributed with independent prognostic value in all patients (P

  11. Pulmonary hypertension in hereditary haemorrhagic telangiectasia

    Institute of Scientific and Technical Information of China (English)

    Veronique; MM; Vorselaars; Sebastiaan; Velthuis; Repke; J; Snijder; Jan; Albert; Vos; Johannes; J; Mager; Martijn; C; Post

    2015-01-01

    Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.

  12. Ion channels and transporters as therapeutic targets in the pulmonary circulation.

    Science.gov (United States)

    Olschewski, Andrea; Papp, Rita; Nagaraj, Chandran; Olschewski, Horst

    2014-12-01

    Pulmonary circulation is a low pressure, low resistance, high flow system. The low resting vascular tone is maintained by the concerted action of ion channels, exchangers and pumps. Under physiological as well as pathophysiological conditions, they are targets of locally secreted or circulating vasodilators and/or vasoconstrictors, leading to changes in expression or to posttranslational modifications. Both structural changes in the pulmonary arteries and a sustained increase in pulmonary vascular tone result in pulmonary vascular remodeling contributing to morbidity and mortality in pediatric and adult patients. There is increasing evidence demonstrating the pivotal role of ion channels such as K(+) and Cl(-) or transient receptor potential channels in different cell types which are thought to play a key role in vasoconstrictive remodeling. This review focuses on ion channels, exchangers and pumps in the pulmonary circulation and summarizes their putative pathophysiological as well as therapeutic role in pulmonary vascular remodeling. A better understanding of the mechanisms of their actions may allow for the development of new options for attenuating acute and chronic pulmonary vasoconstriction and remodeling treating the devastating disease pulmonary hypertension.

  13. The TL,NO/TL,CO ratio cannot be used to exclude pulmonary embolism

    NARCIS (Netherlands)

    Fabius, Timon M.; Eijsvogel, Michiel M.; van der Lee, Ivo; Brusse-Keizer, Marjolein; de Jongh, Franciscus H.C.

    2016-01-01

    Background The existing screening modalities for pulmonary embolism (PE), such as D-dimer and clinical prediction rules, have low positive predictive values. With its capability to indicate pulmonary vascular abnormalities, the ratio of the transfer factor of the lungs for nitric oxide and the

  14. Quantification and Visualization of Variation in Anatomical Trees

    Energy Technology Data Exchange (ETDEWEB)

    Amenta, Nina; Datar, Manasi; Dirksen, Asger; de Bruihne, Marleen; Feragen, Aasa; Ge, Xiaoyin; Holst Pedersen, Jesper; Howard, Marylesa; Owen, Megan; Petersen, Jens; Shi, Jie; Xu, Qiuping

    2015-07-01

    This paper presents two approaches to quantifying and visualizing variation in datasets of trees. The first approach localizes subtrees in which significant population differences are found through hypothesis testing and sparse classifiers on subtree features. The second approach visualizes the global metric structure of datasets through low-distortion embedding into hyperbolic planes in the style of multidimensional scaling. A case study is made on a dataset of airway trees in relation to Chronic Obstructive Pulmonary Disease.

  15. Effect of Xuebijing Injection on Vascular Endothelial Growth Factor in Peripheral Blood in Patients with Severe Pulmonary Contusion%血必净注射液对严重肺挫伤患者外周血中血管内皮生长因子的影响

    Institute of Scientific and Technical Information of China (English)

    韩冬; 黄伟

    2014-01-01

    Objective To observe the effect of Xuebijing injection on vascular endothelial growth factor ( VEGF) in peripheral blood in patients with severe pulmonary contusion. Methods A total of 65 patients with severe pulmonary contusion in the Third People's Hospital of Wuxi during September 2011 and January 2014 were randomly di-vided into observation group ( n=31 ) and control group ( n=34 ) . The control group received routine comprehensive treatment. Based on the routine comprehensive treatment, the observation group was treated with 50 ml Xuebijing injec-tion diluted with 100 ml of physiological saline twice a day, and one course of treatment was 7 d. The serum VEGF levels were detected on 1st d, 3rd d, 5th d and 7th d after injuries by enzyme linked immunosorbent assay (ELISA)respectively, and related clinical indexes in the two groups were compared. Results The serum VEGF level changed dynamically in observation group, and it decreased gradually on 1st d after injury. Compared with those in control group, the differences of VEGF levels on 3rd d, 5th d and 7th d after injuries were statistically significant (P  观察组血清VEGF含量呈动态变化,伤后第1天开始逐渐下降,与对照组相比,在第3、5、7天的差异均有统计学意义(P<0.01)。观察组全身炎症反应综合征(SIRS)发生率、机械通气率和病死率均显著低于对照组(P<0.05),机械通气时间、住院时间也均显著短于对照组(P<0.05)。结论血必净注射液能够降低严重肺挫伤患者外周血中VEGF水平,从而减轻VEGF高表达所带来的肺损伤,明显改善预后,值得临床推广应用。

  16. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    Science.gov (United States)

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

  17. A Case of Pulmonary Artery Aneurysm Associated with Patent Ductus Arteriosus : Detection by Radionuclide Cardiac Angiography

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, I.; Lee, M. C.; Cho, B. Y.; Koh, C. S.; Yoon, Y. S.; Hong, C. Y.; Rho, J. R.; Youn, K. M.; Han, M. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1981-09-15

    A Case of main pulmonary artery aneurysm in a 9-year-old boy with patent ductus arteriosus is presented. In this case presented with a huge mass density on the chest X-ray, radionuclide cardiac angiography showed a vascular lesion, which was confirmed as an aneurysm of the main pulmonary artery at roentgenologic angiogram. The aneurysm appeared following an episode of bacterial endocarditis and pulmonary hypertension. A successful aneurysmectomy with multiple ligation of ductus arteriosus was performed.

  18. Diagnosis and management of cardiogenic pulmonary edema.

    Science.gov (United States)

    Alwi, Idrus

    2010-07-01

    Acute cardiogenic pulmonary edema (ACPE) is a common cardiogenic emergency with a quite