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Sample records for experimental pulmonary arterial

  1. [Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension].

    Science.gov (United States)

    Zhang, Shujuan; Zhao, Qingyan; Jiang, Xuejun; Yang, Bo; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Yu, Shengbo; Tang, Yanhong; Hu, Wei; Huang, Congxin

    2015-04-14

    To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). 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 underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all PRSD group ((46±8) and (67±9) pg/ml) (all PRSD dogs. RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

  2. α-Solanine reverses pulmonary vascular remodeling and vascular angiogenesis in experimental pulmonary artery hypertension.

    Science.gov (United States)

    Nie, Xiaowei; Dai, Youai; Tan, Jianxin; Chen, Yuan; Qin, Guowei; Mao, Wenjun; Zou, Jian; Chang, Yanhua; Wang, Qian; Chen, Jingyu

    2017-12-01

    Similar to cancer, pulmonary arterial hypertension (PAH) is characterized by vascular remodeling, which leads to obliteration of the small pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor suppressor genes is closely associated with susceptibility to PAH. We hypothesized that α-solanine, a glycoalkaloid found in members of the nightshade family known to have antitumor activity in different cancers, reverses experimental PAH by activating the tumor suppressor-axis inhibition protein 2 (AXIN2). We investigated the effects of α-solanine on PASMC proliferation and apoptosis by using 5-ethynyl-2'-deoxyuridine proliferation assay, proliferating cell nuclear antigen and Ki67 staining, TUNEL and Anexine V assays. Scratch wound healing and tube formation assays were also used to study migration of endothelial cells. In vitro, we demonstrated, using cultured human PASMC from PAH patients, that α-solanine reversed dysfunctional AXIN2, β-catenin and bone morphogenetic protein receptor type-2 signaling, whereas restored [Ca]i, IL-6 and IL-8, contributing to the decrease of PAH-PASMC proliferation and resistance to apoptosis. Meanwhile, α-solanine inhibits proliferation, migration and tube formation of PAH-pulmonary artery endothelial cells by inhibiting Akt/GSK-3α activation. In vivo, α-solanine administration decreases distal pulmonary arteries remodeling, mean pulmonary arteries pressure and right ventricular hypertrophy in both monocrotaline-induced and Sugen/hypoxia-induced PAH in mice. This study demonstrates that AXIN2/β-catenin axis and Akt pathway can be therapeutically targeted by α-solanine in PAH. α-Solanine could be used as a new therapeutic strategy for the treatment of PAH.

  3. 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

  4. 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 ...

  5. 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.

  6. VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension

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    Szema Anthony M

    2011-10-01

    Full Text Available Abstract Background Pulmonary Arterial Hypertension (PAH remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1 Can VIP protect against PH in other experimental models? and 2 Does combining VIP with an endothelin (ET receptor antagonist bosentan enhance its efficacy? Methods Within 3 weeks of a single injection of monocrotaline (MCT, s.c. in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o. alone, with VIP (i.p. alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival. Results Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days. Conclusions 1 VIP completely prevented and significantly reversed MCT-induced PAH; 2 VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3 combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway.

  7. Pulmonary artery aneurysm

    African Journals Online (AJOL)

    Enrique

    2). An echocardiogram confirmed pulmonary valvular stenosis with post-stenotic dilatation and pul- monary artery aneurysm formation. The pulmonary valve pressure gradi- ent was > 28 mmHg. The patient set- tled on low-dose diuretic therapy, and following cardiothoracic surgical con- sultation it was decided that no surgi-.

  8. Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

    2015-11-01

    Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

  9. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.

  10. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Nobutoshi Nawa

    2016-01-01

    Full Text Available We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M, which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH. In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.

  11. Pulmonary artery sling: Case report

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    Shin, Gil Hyun; Lee, Sun Wha; Cha, Sung Ho [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1993-09-15

    Aberrant left-sided pulmonary artery(pulmonary artery sling) is an uncommon anomaly,which may cause significant respiratory abnormality. We report a case of pulmonary artery sling which is combined with persistent left superior vena cava and dextrocardia. This case were identified by esophagogram and CT and confirmed by MRI and angiography. We consider that MRI is a valuable new method for the diagnosis of aberrant left-sided pulmonary artery.

  12. Pulmonary artery haemorrhage in newborn calves following bluetongue virus serotype 8 experimental infections of pregnant heifers.

    Science.gov (United States)

    Martinelle, Ludovic; Dal Pozzo, Fabiana; Sarradin, Pierre; De Leeuw, Ilse; De Clercq, Kris; Thys, Christine; Thiry, Etienne; Saegerman, Claude

    2013-12-27

    The emergence of bluetongue disease (BT) among livestock in Europe in 2006 raised many questions including the occurrence and epidemiological significance of foetal infections in cattle. To clarify these aspects, vaccinated and unvaccinated pregnant heifers were sequentially infected twice in an isolation facility (biosafety level 3) with a northern European outbreak strain of Bluetongue virus serotype 8 (BTV-8). The study was terminated 2 months after calving with necropsy of the dams and their offspring. The cattle were monitored throughout the study by clinical scoring and for the presence of circulating neutralising antibodies, and after calving for the presence of infectious virus and viral RNA in blood and milk. Four calves, one born from a vaccinated dam and three from non-vaccinated ones, that were infected at 120 days of gestation had obvious haemorrhage of the pulmonary artery at necropsy. Although haemorrhage of the pulmonary artery is highly characteristic of BT, viral RNA was not detected in any of these calves. Furthermore, although none of the calves born from heifers infected prior to mid-gestation had teratogenic BTV typical brain lesions, some had lesions at birth suggestive of in utero BTV infection. Despite the lack of viral RNA detection, the presence of haemorrhage of the pulmonary artery deserves to be reported as a new observation in the context of the multiple investigations having as main subject the BTV placental crossing in cattle. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Cardiac "fitness" training: an experimental comparative study of three methods of pulmonary artery banding for ventricular training.

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    Le Bret, Emmanuel; Lupoglazoff, Jean Marc; Borenstein, Nicolas; Fromont, Gaelle; Laborde, François; Bachet, Jean; Vouhé, Pascal

    2005-01-01

    When the left ventricle is unable to sustain a systemic pressure in transposition of the great arteries (TGA), left ventricular retraining is mandatory before the morphologic left ventricle under the aorta is switched. This is currently achieved by creating a ventricular overload through pulmonary artery banding, usually associated with an aortopulmonary shunt in case of a TGA with an intact ventricular septum. Our experimental study compared three different modes of increased ventricular afterload to obtain ventricular hypertrophy. Fifteen lambs (mean weight 48 kg) underwent pulmonary artery banding. Five animals (group I) received a classic band; 5 (group II) received a classic band which was adjusted at week 1 and 3; and 4 (group III) received a band which was tightened for 1 hour, twice a day (early morning and late afternoon). After 5 weeks, the lambs were evaluated hemodynamically before they were sacrificed and their hearts harvested for histologic examination. No difference was noted in the hemodynamic data between groups 1 and II. Group III showed a greater ability to increase ventricular pressure in this model. No significant difference was noted between the three groups in terms of macroscopic alterations, but all animals demonstrated an increase in right ventricular wall thickness compared with control animals. Several fibrosis areas were evident in group I and II but none in group III. Intermittent pulmonary artery banding is able to induce hemodynamically sufficient ventricular hypertrophy without fibrosis.

  14. Pulmonary artery intramural leiomyosarcoma mimicking pulmonary aneurysm.

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    Kanaoka, Rie; Takahashi, Yusuke; Morita, Shigeki; Dejima, Hitoshi; Matsutani, Noriyuki; Kawamura, Masafumi

    2016-11-01

    Chest radiography indicated a well-defined rounded mass at the left lung hilum in a 77-year-old former smoker. Chest computed tomography revealed a longitudinal saccular enlargement of the left pulmonary artery with surrounding soft tissue opacity. Resection of the left lower lobe with segment 1 + 2c was carried out to completely remove the dilated pulmonary artery. The resected specimen revealed obvious dilatation of the interlobar pulmonary artery and its branches. A small yellowish well-demarcated myxoid tumor was contained in this lesion, which was diagnosed as a primary pulmonary artery intramural leiomyosarcoma. © The Author(s) 2016.

  15. Anomalous left coronary artery from the pulmonary artery

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    ... of the left coronary artery arising from the pulmonary artery; ALCAPA; ALCAPA syndrome; Bland-White-Garland syndrome; ... children with ALCAPA, the LCA originates from the pulmonary artery. The pulmonary artery is the major blood ...

  16. Genetics Home Reference: pulmonary arterial hypertension

    Science.gov (United States)

    ... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  17. Management of iatrogenic pulmonary artery injury during pulmonary artery banding

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    Neeti Makhija

    2017-01-01

    Full Text Available Pulmonary Artery banding (PAB is limited to selected patients who cannot undergo primary repair due to complex anatomy, associated co-morbidities, as a part of staged univentricular palliation, and for preparing the left ventricle prior to an arterial switch operation. We report a catastrophic iatrogenic complication in which the pulmonary artery was injured during the PAB. We discuss its multi-pronged management.

  18. Management of Iatrogenic Pulmonary Artery Injury during Pulmonary Artery Banding

    Science.gov (United States)

    Makhija, Neeti; Aggarwal, Shivani; Talwar, Sachin; Ladha, Suruchi; Das, Deepanwita; Kiran, Usha

    2017-01-01

    Pulmonary Artery banding (PAB) is limited to selected patients who cannot undergo primary repair due to complex anatomy, associated co-morbidities, as a part of staged univentricular palliation, and for preparing the left ventricle prior to an arterial switch operation. We report a catastrophic iatrogenic complication in which the pulmonary artery was injured during the PAB. We discuss its multi-pronged management. PMID:28701613

  19. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

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    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  20. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension.

    Science.gov (United States)

    Dorfmüller, Peter; Chaumais, Marie-Camille; Giannakouli, Maria; Durand-Gasselin, Ingrid; Raymond, Nicolas; Fadel, Elie; Mercier, Olaf; Charlotte, Frédéric; Montani, David; Simonneau, Gérald; Humbert, Marc; Perros, Frédéric

    2011-09-09

    Involvement of inflammation in pulmonary hypertension (PH) has previously been demonstrated and recently, immune-modulating dendritic cells (DCs) infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH) and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS), as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT), monocrotaline-exposure/pneumonectomy (MCT/PE). Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine) in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature. Immunolabeling for OX62, CD68 and actin revealed

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

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    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

  2. Management of pulmonary arterial hypertension.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2013-02-01

    Pulmonary arterial hypertension (PAH) is a complex disease with a high mortality. Management of this disease is underpinned by supportive and general therapies delivered by multidisciplinary teams in specialist centres. In recent years, a number of PAH-specific therapies have improved patient outcomes. This article will discuss the management of PAH in the context of relevant recently published studies in this area.

  3. Pulmonary Artery Catheter Placement Using Transesophageal Echocardiography.

    Science.gov (United States)

    Cronin, Brett; Robbins, Robin; Maus, Timothy

    2017-02-01

    To assess the feasibility of pulmonary artery catheter placement using transesophageal echocardiography inclusive of a description of the technique. A prospective, proof-of-concept study. Single university hospital. Twenty patients with chronic thromboembolic pulmonary hypertension scheduled for pulmonary thromboendarterectomy. Pulmonary artery catheters were placed in 20 patients solely by transesophageal echocardiographic guidance. Placement of the pulmonary artery catheter in the pulmonary artery with transesophageal echocardiography guidance in fewer than 10 minutes was considered successful placement. The time to placement was measured from advancement of the pulmonary artery catheter in the superior vena cava (20 cm) to a final location at the junction of the right pulmonary artery and main pulmonary artery. All 20 pulmonary artery catheters were placed successfully using transesophageal echocardiography guidance and the median time to placement was 43 seconds. In 9 of the 20 patients (45%), the catheter was placed successfully on the first attempt without any adjustments. However, in 9 others (45%), the catheter required manipulation under transesophageal echocardiography vision. In 3 patients (15%), the pulmonary artery catheter was observed to be coiled in the right atrium and in 1 instance (5%) manipulation of the catheter in the right ventricle was required to enter the outflow tract. Transesophageal echocardiography is a viable adjunctive method to conventional pressure waveform placement of pulmonary artery catheters in potentially difficult patients. Published by Elsevier Inc.

  4. Pulmonary Artery Dissection: A Fatal Complication of Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Chuanchen Zhang

    2016-01-01

    Full Text Available Pulmonary artery dissection is extremely rare but it is a really life-threatening condition when it happens. Most patients die suddenly from major bleeding or tamponade caused by direct rupture into mediastinum or retrograde into the pericardial sac. What we are reporting is a rare case of a 46-year-old female patient whose pulmonary artery dissection involves both the pulmonary valve and right pulmonary artery. The patient had acute chest pain and severe dyspnea, and the diagnosis of pulmonary artery dissection was confirmed by ultrasonography and CT angiography. Moreover, its etiology, clinical manifestations, and management are also discussed in this article.

  5. 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.

    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

  6. Differential imaging features of pulmonary artery dissection from other intraluminal diseases of pulmonary artery: Two cases report

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    Park, Joo Ho; Shin, Hyun Woong; Sohn, Kung Rak; Lee, Yil Gi [Daegu Fatima Hospital, Daegu(Korea, Republic of)

    2015-03-15

    Pulmonary artery dissection is rarer than other intraluminal diseases of pulmonary artery such as pulmonary thromboembolism or pulmonary artery sarcoma. We report two cases of pulmonary artery dissection mimicking pulmonary artery sarcoma. Computed tomography (CT) showed no enhancement of intrapulmonary arterial lesion or expansion of involved pulmonary artery. Magnetic resonance imaging (MRI) showed low-signal intensity intimal flap on T1- and T2-weighted images. There was no fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)-CT. In this case report, we describe the imaging features of pulmonary artery dissection on CT, MRI, and PET-CT.

  7. Pulmonary arterial hypertension in children after neonatal arterial switch operation

    NARCIS (Netherlands)

    Zijlstra, Willemijn MH; Elmasry, Ola; Pepplinkhuizen, Shari; Ivy, D Dunbar; Bonnet, Damien; Lévy, Marilyne; Gavilan, Jose Luis; Torrent-Vernetta, Alba; Mendoza, Alberto; Del Cerro, Maria Jesus; Moledina, Shahin; Berger, Rolf M. F.

    OBJECTIVES: Paediatric pulmonary arterial hypertension (PAH) after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA) is a clinically recognised entity with an estimated incidence of 0.6%-1.0%. Nevertheless, a clinical characterisation is lacking. We present an

  8. Pulmonary endothelial cell DNA methylation signature in pulmonary arterial hypertension.

    Science.gov (United States)

    Hautefort, Aurélie; Chesné, Julie; Preussner, Jens; Pullamsetti, Soni S; Tost, Jorg; Looso, Mario; Antigny, Fabrice; Girerd, Barbara; Riou, Marianne; Eddahibi, Saadia; Deleuze, Jean-François; Seeger, Werner; Fadel, Elie; Simonneau, Gerald; Montani, David; Humbert, Marc; Perros, Frédéric

    2017-08-08

    Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH ( n = 11), heritable PAH ( n = 10) and controls ( n = 18). DNA methylation was assessed using the Illumina HumanMethylation450 Assay. After normalization, samples and probes were clustered according to their methylation profile. Differential clusters were functionally analyzed using bioinformatics tools. Unsupervised hierarchical clustering allowed the identification of two clusters of probes that discriminates controls and PAH patients. Among 147 differential methylated promoters, 46 promoters coding for proteins or miRNAs were related to lipid metabolism. Top 10 up and down-regulated genes were involved in lipid transport including ABCA1, ABCB4, ADIPOQ, miR-26A, BCL2L11. NextBio meta-analysis suggested a contribution of ABCA1 in PAH. We confirmed ABCA1 mRNA and protein downregulation specifically in PAH PEC by qPCR and immunohistochemistry and made the proof-of-concept in an experimental model of the disease that its targeting may offer novel therapeutic options. In conclusion, DNA methylation analysis identifies a set of genes mainly involved in lipid transport pathway which could be relevant to PAH pathophysiology.

  9. Pulmonary Artery Leiomyosarcoma Diagnosed without Delay

    Directory of Open Access Journals (Sweden)

    Motohisa Yamasaki

    2011-05-01

    Full Text Available A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma. Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.

  10. Unusual migration of pulmonary artery catheter

    Directory of Open Access Journals (Sweden)

    Sanjay Kuravinakop

    2007-01-01

    Full Text Available Pulmonary artery catheter is widely used in intensive care. Distal migration of the catheter is a know complication. Diagnosis of such a migration is made by both clinical criteria and radiographs. A 55 year old septic lady was admitted to the intensive care unit. Pulmonary artery catheter introduced for cardiac output monitoring migrated from right lung to left lung. Diagnosis was made following a chest radiograph the following day of insertion with the clinical criteria remaining unaltered. Migration of pulmonary artery catheter can occur not only distally but from one lung to another. Clinical criteria alone cannot rule out migration. Chest radiographs form an important part in monitoring the position of the pulmonary artery catheter.

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

    Science.gov (United States)

    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

    2012-04-01

    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 important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension. Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction. The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

  12. 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

  13. Lineage Analysis in Pulmonary Arterial Hypertension

    Science.gov (United States)

    2012-06-01

    cells. We induced experimental pulmonary hypertension in SM22 Cre x mT/mG mice, by injecting monocrotaline pyrrole into the pulmonary circulation of...were observed in the pulmonary vascular lesions in monocrotaline -injected rats (Sahara 2007).   Endothelial to mesenchymal transition refers to...relative to the induction of experimental pulmonary hypertension : a) Acquisition and breeding of VE Cadherin CreER-T2 tamoxifen- inducible conditional Cre

  14. Anomalous left the pulmonary dilemma coronary artery artery from a ...

    African Journals Online (AJOL)

    ; 8: 787-80I. 6. Wilson CL, Dlabal PW, Holeyfield RW, Akins CW, Knauf DG. Anomalous origin of left coronary artery from pulmonary artery: case report and review of. lileralUre concerning teenagers and adults.J Thorac Cardicn'asc SlIrg 1977; ...

  15. Idiopathic aneurysm of pulmonary artery

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, Julio B. Cota; Pimentel, Patricia N.; Knust, Beatriz S., E-mail: jcota@uol.com.br [Clinica de Cardiologia Cota Pacheco, Mogi das Cruzes, SP (Brazil)

    2015-07-15

    Because it is a very rare isolated lesion, we decided to present this case of idiopathic pulmonary artery aneurysm (IPAA) and review the cases published in the literature in order to correlate our clinical and imaging findings, as well as management based on patient data. IPAA was first described in a case of autopsy by Bristowe in 1860 and later in 1947 by Deterling and Claggett, whose prevalence was lower than eight to one hundred thousand. Although the use of diagnostic imaging methods has been applied in a very large population in recent decades, this lesion has been most often described in postmortem examinations. Therefore, it is important to be aware of possible clinical symptoms, at times non-specific, as well as the signs on imaging studies. In this study, therefore, the report of a case of an asymptomatic patient whose diagnosis was done through color Doppler echocardiography in a routine test in 2012, later confirmed by simple chest computed tomography (chest CT) and cardiac catheterization as IPAA and its branches. We discussed the literature available and the possibilities for treatment and the use of color Doppler echocardiography as an initial diagnostic tool for such a rare and intriguing disease. (author)

  16. Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric dysfunction

    NARCIS (Netherlands)

    Manders, E.; Man, F.S. de; Handoko, M.L.; Westerhof, N.; Hees, H.W.H. van; Stienen, G.J.; Vonk-Noordegraaf, A.; Ottenheijm, C.A.C.

    2012-01-01

    We previously demonstrated that diaphragm muscle weakness is present in experimental pulmonary arterial hypertension (PH). However, the nature of this diaphragm weakness is still unknown. Therefore, the aim of this study was to investigate whether changes at the sarcomeric level contribute to

  17. Promoting Pulmonary Arterial Growth via Right Ventricle-to-Pulmonary Artery Connection in Children With Pulmonary Atresia, Ventricular Septal Defect, and Hypoplastic Pulmonary Arteries.

    Science.gov (United States)

    Rabinowitz, Edon J; Epstein, Shilpi; Kohn, Nina; Meyer, David B

    2017-09-01

    Complete repair of pulmonary atresia (PA) ventricular septal defect (VSD) with hypoplastic or absent native pulmonary arteries, often with major aortopulmonary collateral arteries (MAPCAs), involves construction of an adequate sized pulmonary arterial tree. We report our results with a previously described staged strategy using initial right ventricle (RV)-to-reconstructed pulmonary arterial tree (RV-PA) connection to promote pulmonary arterial growth and facilitate later ventricular septation. We retrospectively reviewed data for all patients (N = 10) with initial echocardiographic diagnosis of PA-VSD and hypoplastic pulmonary arteries operated in our center from October 2008 to August 2016. Pulmonary arterial vessel size measured on preoperative and postoperative angiography was used to calculate Nakata index. Seven patients had PA-VSD, three had virtual PA-VSD, and seven had MAPCAs. All underwent creation of RV-PA connection at a median age of 7.5 days and weight 3.6 kg. Eight patients had RV-PA conduits, two had a transannular patches, and seven had major pulmonary artery reconstruction simultaneously. There were no deaths or serious morbidity; one conduit required revision prior to complete repair. Complete repair with ventricular septation and RV pressure less than half systemic was achieved in all patients at a median age of 239 days. Nakata index in neonatal period was 54 mm2/m2 (range 15-144 mm2/m2) and at time of septation 184 mm2/m2 (range 56-510 mm2/m2; P = .004). Growth rates of right and left branch pulmonary arteries were similar. The 10 patients underwent 28 catheterizations with 13 interventions in 8 patients prior to full repair. Early palliative RV-PA connection promotes pulmonary arterial growth and facilitates eventual full repair with VSD closure with low RV pressure and operative risk.

  18. Acquired pulmonary artery stenosis in four dogs.

    Science.gov (United States)

    Scansen, Brian A; Schober, Karsten E; Bonagura, John D; Smeak, Daniel D

    2008-04-15

    4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.

  19. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance

    NARCIS (Netherlands)

    Rol, N.; Timmer, E.M.; Faes, T.J.; Noordegraaf, A.V.; Grunberg, K.; Bogaard, H.J.; Westerhof, N.

    2017-01-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall

  20. Endothelin receptor antagonists for pulmonary arterial hypertension.

    Science.gov (United States)

    Liu, C; Chen, J

    2006-07-19

    Pulmonary arterial hypertension (PAH) is a devastating disease, which leads to right heart failure and premature death. Pulmonary arterial hypertension can be classified into five categories according to Venice classification: (1) Idiopathic PAH; (2) Familial PAH; (3) PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, HIV infection, drugs and toxins or other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); (4) PAH associated with significant venous or capillary involvement, which includes pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH); (5) Persistent pulmonary hypertension of the newborn. PAH can also be secondary to chronic hypoxic lung disease as part of the "cor-pulmonale" syndrome, and also secondary to left sided heart disease, but these conditions are usually distinguished from those listed here. To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. A search was carried out using the CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of August 2005. Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension (PAH) were selected by two reviewers. Two reviewers independently selected studies; assessed study quality; and extracted data. We analysed outcomes as continuous and dichotomous data. In this updated version of the review, we added two RCTs. Altogether, five RCTs met the entry criteria of the review (reporting eight group comparisons). The studies were of short duration (12-16 weeks), recruiting a total of 482 participants. Three studies compared a non-selective ERA (bosentan) with placebo, one compared bosentan with sildenafil (a

  1. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology

    Directory of Open Access Journals (Sweden)

    M. Humbert

    2010-03-01

    Full Text Available Pulmonary arterial hypertension (PAH and chronic thromboembolic pulmonary hypertension (CTEPH are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2, HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis, and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy.

  2. Identity crisis in pulmonary arterial hypertension.

    Science.gov (United States)

    Ruffenach, G; Bonnet, S; Rousseaux, S; Khochbin, S; Provencher, S; Perros, F

    2018-01-01

    Pulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer cells acquire their hallmarks by a pathological Darwinian evolution process built on the so-called cancer cell "identity crisis." Here we demonstrate that PAH shares the most striking features of the cancer identity crisis: the ectopic expression of normally silent tissue-specific genes.

  3. Management of Pulmonary Arterial Hypertension in Children

    NARCIS (Netherlands)

    Roofthooft, M. T. R.; van Loon, R. L. E.; Berger, R. M. F.

    2010-01-01

    In this review we discuss the new anti- Pulmonary Arterial Hypertension [PAH] drugs and the available data on their use in paediatric PAH. Treatment of patients with PAH, children and adults, is aimed at a reduction of symptoms, survival and improvement of haemodynamics as well as exercise capacity.

  4. 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.

  5. Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Antigny, Fabrice; Hautefort, Aurélie; Meloche, Jolyane; Belacel-Ouari, Milia; Manoury, Boris; Rucker-Martin, Catherine; Péchoux, Christine; Potus, François; Nadeau, Valérie; Tremblay, Eve; Ruffenach, Grégoire; Bourgeois, Alice; Dorfmüller, Peter; Breuils-Bonnet, Sandra; Fadel, Elie; Ranchoux, Benoît; Jourdon, Philippe; Girerd, Barbara; Montani, David; Provencher, Steeve; Bonnet, Sébastien; Simonneau, Gérald; Humbert, Marc; Perros, Frédéric

    2016-04-05

    Mutations in the KCNK3 gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH). KCNK3 encodes an outward rectifier K(+) channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH). We demonstrated that KCNK3 expression and function were reduced in human PAH and in monocrotaline-induced PH in rats. Using a patch-clamp technique in freshly isolated (not cultured) pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, we found that KCNK3 current decreased progressively during the development of monocrotaline-induced PH and correlated with plasma-membrane depolarization. We demonstrated that KCNK3 modulated pulmonary arterial tone. Long-term inhibition of KCNK3 in rats induced distal neomuscularization and early hemodynamic signs of PH, which were related to exaggerated proliferation of pulmonary artery endothelial cells, pulmonary artery smooth muscle cell, adventitial fibroblasts, and pulmonary and systemic inflammation. Lastly, in vivo pharmacological activation of KCNK3 significantly reversed monocrotaline-induced PH in rats. In PAH and experimental PH, KCNK3 expression and activity are strongly reduced in pulmonary artery smooth muscle cells and endothelial cells. KCNK3 inhibition promoted increased proliferation, vasoconstriction, and inflammation. In vivo pharmacological activation of KCNK3 alleviated monocrotaline-induced PH, thus demonstrating that loss of KCNK3 is a key event in PAH pathogenesis and thus could be therapeutically targeted.

  6. Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Andersen, Kasper Hasseriis; Andersen, Claus Bøgelund; Gustafsson, Finn

    2017-01-01

    Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive...... pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH......) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic...

  7. [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. © 2013 médecine/sciences – Inserm.

  8. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  9. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    Science.gov (United States)

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. PMID:24533144

  10. 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.

  11. Endovascular Thrombin Injection for a Pulmonary Artery Pseudoaneurysm: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jin Ho; Shin, Ji Hoon; Yoon, Hyun Ki [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2011-12-15

    Massive hemoptysis caused by pulmonary artery pseudoaneurysms is uncommon, and endovascular treatment such as coil embolization is the first choice for treating pulmonary artery pseudoaneurysms. Various embolic agents could be used according to the angiographic findings, yet embolization with thrombin injection is very rare. Herein, we describe a case of a pulmonary artery pseudoaneurysm that was successfully treated by endovascular thrombin injection using a microcatheter because of the difficulty in performing a coil embolization due to a short feeding artery.

  12. Isolated Unilateral Absent Branch Pulmonary Artery with Peripheral Pulmonary Stenosis and Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Sunil Abhishek B

    2017-09-01

    Full Text Available Isolated Unilateral Absent Pulmonary Artery (UAPA is a rare congenital anomaly. It is usually associated with congenital heart defects. A 45 year old male patient presented with complaints of fever with cough and expectoration for 15 days and retrosternal chest discomfort for the previous 2 days. ECG showed diffuse ST segment depression with T wave inversion in the inferior and lateral leads. Coronary Angiogram done through the right femoral approach revealed diffusely diseased Left Anterior Descending (LAD artery that was totally cut off at the mid segment. The Left Circumflex (LCx artery was providing blood supply to the right middle and lower lung areas. There was another collateral arising from the Left Subclavian Artery supplying the right middle and lower lung areas. The left pulmonary artery was normal, but branches supplying the middle and lower lobes of the right lung were absent and the upper lobe branch had pulmonary stenosis. UAPA is a rare clinical entity; collaterals from coronaries are extremely rare in this condition and till now there has not been any case report of unilateral absent branch pulmonary artery with peripheral stenosis of other branches, on the affected side and associated coronary artery disease.

  13. Adrenomedullin alleviates pulmonary artery collagen accumulation in rats with pulmonary hypertension induced by high blood flow.

    Science.gov (United States)

    Pang, Lulu; Qi, Jianguang; Gao, Yang; Jin, Hongfang; Du, Junbao

    2014-04-01

    Collagen accumulation is one of the important pathologic changes in the development of pulmonary hypertension. Previous research showed that adrenomedullin (ADM) mitigates the development of pulmonary hypertension. The present study explored the role of ADM in the development of pulmonary artery collagen accumulation induced by high pulmonary blood flow, by investigating the effect of ADM [1.5 μg/(kg h)] subcutaneously administered by mini-osmotic pump on pulmonary hemodynamics, pulmonary vascular structure and pulmonary artery collagen accumulation and synthesis in rats with high pulmonary blood flow induced by aortocaval shunting. The results showed that ADM significantly decreased mean pulmonary artery pressure (mPAP) and the ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+SP)], attenuated the muscularization of small pulmonary vessels and relative medial thickness (RMT) of pulmonary arteries in rats with high pulmonary blood flow. Meanwhile, ADM ameliorated pulmonary artery collagen deposition represented by a decrease in lung tissue hydroxyproline, collagens I and III content and pulmonary artery collagens I and III expression, reduced collagen synthesis represented by a decrease in lung tissue procollagens I and III mRNA expression. The results suggest that ADM plays a protective role in the development of pulmonary hypertension induced by high blood flow, by inhibiting pulmonary procollagen synthesis and alleviating pulmonary artery collagen accumulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Copper Dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans

    Science.gov (United States)

    Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A.; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C.; Humbert, Marc; Noordegraaf, Anton Vonk; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F.

    2012-01-01

    Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation–induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide–1 inhibition or lysyl–oxidase–1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension. PMID:22162909

  15. Pulmonary Artery Cement Embolism after a Vertebroplasty

    Directory of Open Access Journals (Sweden)

    Anas Nooh

    2015-01-01

    Full Text Available Background Context. Vertebroplasty is a minimally invasive procedure most commonly used for the treatment of vertebral compression fractures. Although it is relatively safe, complications have been reported over time. Among those complications, massive cement pulmonary embolism is considered a rare complication. Here we report a case of massive diffuse cement pulmonary embolism following percutaneous vertebroplasty for a vertebral compression fracture. Study Design. Case report. Methods. This is a 70-year-old female who underwent vertebroplasty for T11 and T12 vertebral compression fracture. Results. CT-scan revealed an incidental finding of cement embolism in the pulmonary trunk and both pulmonary arteries. Since the patient was asymptomatic, she was monitored closely and she did not need any intervention. Conclusion. Vertebroplasty is a minimally invasive procedure used for treatment of vertebral compression fracture. Despite the low rate of complications, a pulmonary cement embolism can occur. The consequences of cement embolism range widely from being asymptomatic to embolism that can cause paralysis, radiculopathy, or a fatal pulmonary embolism.

  16. Ambulatory pulmonary arterial pressure in primary pulmonary hypertension: variability, relation to systemic arterial pressure, and plasma catecholamines.

    OpenAIRE

    Richards, A M; Ikram, H; Crozier, I G; Nicholls, M G; Jans, S

    1990-01-01

    The variability of pulmonary arterial pressure, the relation of pulmonary pressure to systemic pressure, pulmonary pressure responses to stimuli (exercise, hypoxia, smoking, free ambulation), and plasma catecholamine responses were assessed in five patients with primary pulmonary hypertension. Ambulatory monitoring techniques provided data for the computerised analysis of continuous, beat-to-beat, direct recordings of both pulmonary and systemic arterial pressures for 8 to 10 hours. The absol...

  17. Thymoquinone attenuates monocrotaline-induced pulmonary artery hypertension via inhibiting pulmonary arterial remodeling in rats.

    Science.gov (United States)

    Zhu, Ning; Zhao, Xuyong; Xiang, Yijia; Ye, Shiyong; Huang, Jie; Hu, Wuming; Lv, Linchun; Zeng, Chunlai

    2016-10-15

    Pulmonary artery remodeling induced by excess proliferation, migration and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs) is a key component in pulmonary artery hypertension (PAH). Thymoquinone (TQ) triggers cancer cells apoptosis through multiple mechanisms. In addition, TQ inhibits migration of human nonsmall-cell lung cancer cells and human glioblastoma cells. In the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms. After 2weeks of monocrotaline injection (MCT, 60mg/kg), Male Sprague-Dawley rats received TQ (8mg/kg, 12mg/kg, 16mg/kg) or olive oil per day for 2weeks. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were examined 4weeks later. In addition, TUNEL, PCNA, α-SMA, Bax and Bcl-2 were detected by immunohistochemistry staining. Bax, Bcl-2, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) MMP2, MMP9 and activation of p38MAPK and NF-κB were assessed by Western blot. MCT-induced an increase in pulmonary blood pressure and right ventricular hypertrophy, which were attenuated by TQ treatment. TQ also blocked MCT-induced pulmonary arterial remodeling, proliferation of PASMCs, elevation of MMP2 and downregulation of ratio of Bax/Bcl-2, cleaved caspase-3 and cleaved PARP. Furthermore, TQ inhibited MCT-induced activation of p38MAPK and NF-κB. TQ ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via p38MAPK/NF-κB signaling pathway in rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Rarefaction and blood pressure in systemic and pulmonary arteries

    OpenAIRE

    Mette S Olufsen; N. A. Hill; VAUGHAN, GARETH D. A.; Sainsbury, Christopher; Johnson, Martin

    2012-01-01

    The effects of vascular rarefaction (the loss of small arteries) on the circulation of blood are studied using a multiscale mathematical model that can predict blood flow and pressure in the systemic and pulmonary arteries. We augmented a model originally developed for the systemic arteries (Olufsen et al. 1998, 1999, 2000, 2004) to (a) predict flow and pressure in the pulmonary arteries, and (b) predict pressure propagation along the small arteries in the vascular beds. The systemic and pulm...

  19. Elastic properties of pulmonary artery in chronic obstructive pulmonary disease

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    S. Ya. Dotsenko

    2017-02-01

    Full Text Available Today chronic obstructive pulmonary disease (COPD is one of the most common diseases with specific pulmonary vascular changes. The aim – to evaluate elastic properties of pulmonary artery (PA and pathogenic mechanisms of disorders in COPD. Materials and methods. Participants were 50 patients with COPD stages 1–3 without comorbidities (32 men and 18 women, average age was 49.8 ± 1.0 years. Control group included 30 healthy people (19 men and 11 women, aged 50.1 ± 1.2 years. PA elastic properties was researched by ultrasound method. Statistical analysis was performed by means of the Statistica® 6.0 for Windows (StatSoft Inc. software using parametric and nonparametric methods. Results. Study data showed that pulmonary arterial pressure (PAP and PA elastic properties were significantly different between subjects with COPD and control group. Thus, pulsatility, compliance and distensibility in CORD were decreased (39.23 ± 1.6 %, 6.4 ± 0.4 mm 2/mmHg and 1.71 ± 0.10 %/mmHg versus 51.4 ± 1.9 %, 11.1 ± 0.5 mm 2/mmHg and 3.30 ± 0.12 %/mmHg in control group, respectively, p < 0.05, and elastic modulus and index stiffness B were increased (65.7 ± 3.7 mmHg and 2.91 ± 0.17 to 31.6 ± 1.2 mmHg and 2.05 ± 0.08, versus 31.6 ± 1.2 mm Hg and 2.05 ± 0.08 in control group, respectively, p < 0.05. Analysis in groups divided by severity of COPD showed that PA elastic properties was not different significantly between subjects with COPD stage-1 and control group. However, several significant differences in PAP and PA elastic properties between subjects with COPD stage-2, COPD stage-3 and control group were found (p < 0.05. Pearson correlation analysis was showed significant relationships between indexes of PA elastic properties and FEV1, indexes of PAP. Conclusions. The changes of PA elastic properties in COPD are accompany by increasing stiffness, thus reduce pulsatility, compliance and elasticity of vascular wall. Detected changes of PA elastic

  20. [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.

  1. [Update pulmonary arterial hypertension : Definitions, diagnosis, therapy].

    Science.gov (United States)

    Sommer, N; Richter, M J; Tello, K; Grimminger, F; Seeger, W; Ghofrani, H A; Gall, H

    2017-09-01

    The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist. The prognosis of the disease is mainly determined by the right heart insufficiency for which there is currently no specific pharmacological treatment. Lung transplantation may be offered as a last option. This review provides an overview of the current European guidelines from 2015 and the recommendations of the Cologne Consensus Conference for pulmonary hypertension from 2016.

  2. Autonomic nervous system involvement in pulmonary arterial hypertension.

    Science.gov (United States)

    Vaillancourt, Mylène; Chia, Pamela; Sarji, Shervin; Nguyen, Jason; Hoftman, Nir; Ruffenach, Gregoire; Eghbali, Mansoureh; Mahajan, Aman; Umar, Soban

    2017-12-04

    Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

  3. Isolated unilateral pulmonary artery hypoplasia with accompanying pulmonary parenchymal findings on CT: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Surin; Cha, Yoon Ki; Kim, Jeung Sook; Kwon, Jae Hyun; Jeong, Yun Jeong [Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang (Korea, Republic of); Kim, Seon Jeong [Dept. of Radiology, Myongji Hospital, Goyang (Korea, Republic of)

    2017-05-15

    Unilateral pulmonary artery hypoplasia or agenesis without congenital cardiovascular anomalies is rare in adults. We report a case of a 36-year-old man with isolated left unilateral pulmonary artery hypoplasia with recurrent hemoptysis. On computed tomography (CT), the left pulmonary artery showed hypoplasia with multiple collateral vessels seen in the mediastinum and the left hemithorax. Also, parenchymal bands and peripheral linear opacities were seen in the affected lung, which were probably due to chronic infarction induced by unilateral pulmonary artery hypoplasia. There are only a few reports focusing on the radiologic findings in the pulmonary parenchyma induced by unilateral pulmonary artery hypoplasia, such as parenchymal bands and peripheral linear opacities. Therefore we report this case, which focused on the CT findings in the pulmonary parenchyma due to isolated unilateral pulmonary artery hypoplasia.

  4. 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.

  5. Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension.

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    Zhijie Wang

    Full Text Available Conduit pulmonary artery (PA stiffening is characteristic of pulmonary arterial hypertension (PAH and is an excellent predictor of mortality due to right ventricular (RV overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior and viscosity (energy dissipation behavior. Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity and damping ratio (related to viscosity in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416 treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ increased and damping ratio (D decreased at a physiologically relevant frequency (10 Hz in hypertensive PAs. The dynamic elastic modulus (E, a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation.

  6. Large pulmonary artery pseudoaneurysm due to lung carcinoma: pulmonary artery pseudoaneurysm.

    Science.gov (United States)

    Camargo, José de Jesus; Camargo, Spencer Marcantonio; Machuca, Tiago Noguchi; Bello, Rodrigo Moreira

    2010-02-01

    We present the case of a 54-year-old patient who presented to our institution 4 months after refusing surgical treatment for a right upper lobe cavitary carcinoma. Weight loss, hemoptysis, and worsening pulsatile chest pain were the complaints. Radiologic restaging surprisingly revealed a large pulmonary artery pseudoaneurysm occupying the whole cavity area. A right pneumonectomy with intrapericardial pulmonary artery ligation was performed. Previous cases are extremely rare and differ from ours as patients presented with advanced lung cancer and thus, were not treated with resection, but with coil embolization.

  7. Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo study with intravascular ultrasound.

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    Edmund M T Lau

    Full Text Available BACKGROUND: There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV afterload in pulmonary arterial hypertension (PAH. We used intravascular ultrasound (IVUS to evaluate the mechanical properties of the elastic pulmonary arteries (PA in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness. METHOD: Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index β. PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy. RESULTS: AT BASELINE, PAH SUBJECTS DEMONSTRATED GREATER STIFFNESS IN ALL MEASURED INDICES COMPARED TO CONTROLS: compliance (1.50±0.11×10(-2 mm(2/mmHg vs 4.49±0.43×10(-2 mm(2/mmHg, p<0.0001, distensibility (0.32±0.03%/mmHg vs 1.18±0.13%/mmHg, p<0.0001, elastic modulus (720±64 mmHg vs 198±19 mmHg, p<0.0001, and stiffness index β (15.0±1.4 vs 11.0±0.7, p = 0.046. Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance (r(2 = 0.82, p<0.0001, and also between mean PAP and distensibility (r(2 = 0.79, p = 0.002. Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness. CONCLUSION: Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness.

  8. Isolated origin of the left internal carotid artery from the pulmonary artery.

    Science.gov (United States)

    Hurley, Michael C; Nguyen, Pamela H; DiPatri, Arthur J; Shaibani, Ali

    2008-09-01

    The authors describe what is, to their knowledge, the first reported case of the anomalous origin of an internal carotid artery from the pulmonary artery. An otherwise asymptomatic 6-year-old girl, who presented with headaches and hypertension, underwent a comprehensive workup that revealed extensive meningeal and cerebral artery anastomoses to the left internal carotid artery--itself arising from the origin of the left pulmonary artery. This unique anatomical anomaly, caused by a disturbed pattern of aortic arch regression, resulted in a right-to-left vascular shunt into the pulmonary artery and a disturbance of intracranial artery flow patterns, complicating the management options.

  9. Early onset of retrograde flow in the main pulmonary artery is a characteristic of pulmonary arterial hypertension.

    Science.gov (United States)

    Helderman, Frank; Mauritz, Gert-Jan; Andringa, Kirsten E; Vonk-Noordegraaf, Anton; Marcus, J Tim

    2011-06-01

    To evaluate if early onset of retrograde flow in the main pulmonary artery is a characteristic of pulmonary arterial hypertension (PAH). Fifty-five patients with suspected pulmonary hypertension (PH) underwent right-sided heart catheterization and retrospectively ECG-gated MR phase-contrast velocity quantification in the main pulmonary artery. Pulmonary hypertension was defined by a mean pulmonary artery pressure being larger than 25 mmHg. The onset time of the retrograde flow relative to the cardiac cycle duration (Relative Onset Time = ROT) was compared with mean pulmonary artery pressure. By the catheterization, 38 patients were identified as having PAH. The ROT for these PAH patients was significantly different from those found in the 17 non-PH subjects (0.14 ± 0.06 versus 0.37 ± 0.06, P < 0.001). The mean pulmonary artery pressure was related to the ROT (r(2) = 0.62, P < 0.001) and could be estimated from the ROT with a standard deviation of 11.7 mmHg. With a cutoff value of 0.25, the ROT distinguished PAH patients from non-PH subjects. Early onset of retrograde flow in the main pulmonary artery is a characteristic of pulmonary arterial hypertension and is visible by standard MR phase-contrast velocity quantification. Copyright © 2011 Wiley-Liss, Inc.

  10. Giant coronary artery aneurysm after Takeuchi repair for anomalous left coronary artery from the pulmonary artery.

    Science.gov (United States)

    Dunlay, Shannon M; Bonnichsen, Crystal R; Dearani, Joseph A; Warnes, Carole A

    2014-01-01

    A 33-year-old woman with an anomalous left coronary artery arising from the pulmonary artery who had undergone Takeuchi repair at age 7 years presented for evaluation. The Takeuchi procedure creates an aortopulmonary window and an intrapulmonary tunnel that baffles the left coronary artery to the aorta. A mediastinal mass was identified as a giant aneurysm of the left coronary artery resulting in compression of the pulmonary artery and left upper pulmonary vein. The patient underwent open repair with patch closure at the aortic entrance of the left coronary Takeuchi repair and resection and evacuation of the aneurysm. A saphenous vein graft to the left anterior descending artery was performed. Postoperative echocardiography demonstrated normal left ventricular function. This is the first reported case of giant aneurysm formation after Takeuchi repair. The reported complications have included the development of pulmonary artery stenosis at the intrapulmonary baffle, baffle leak, decreased left ventricular function, and mitral regurgitation. In conclusion, late complications of the Takeuchi procedure are common, underscoring the importance of lifelong follow-up at a center with experience in treating coronary anomalies. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Pulmonary artery catheter entrapment in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Alsatli Raed

    2010-01-01

    Full Text Available A pulmonary artery catheter (PAC is an important tool in the preoperative cardiac management, and it provides measurements which helps in the patient management During open heart surgery the catheter tends to rest against the anterior lateral wall of the right atrium where the catheter may be caught by a suture in the cannulation for cardiopulmonary bypass. We describe a very rare complication which is inadvertent surgical suturing of the PAC to the inferior vena cava that necessitated reopening the chest, cutting, the suture and removing the catheter.

  12. Future perspectives in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gérald Simonneau

    2016-12-01

    Full Text Available While there have been advances in the field of pulmonary arterial hypertension (PAH, disease management remains suboptimal for many patients. The development of novel treatments and strategies can provide opportunities to target other mechanisms that play a role in the complex pathobiology of PAH outside of the three main pathophysiological pathways. In this review, we highlight some of the potential PAH therapies or techniques that are being, or have been, investigated in phase II clinical trials. This review also discusses potential points for consideration in the development of novel therapies that target putative disease mediators or modifiers.

  13. Abstract 13972: Dexmedetomidine Ameliorates Monocrotaline Induced Pulmonary Arterial Hypertension in Rats

    National Research Council Canada - National Science Library

    Kajikawa, Yusuke; Hosokawa, Susumu; Wakabayashi, Kenji; Maejima, Yasuhiro; Isobe, Mitsuaki; Doi, Shouzaburoh

    2015-01-01

    [Introduction] Pulmonary arterial hypertension (PAH) is characterized by increased proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Dexmedetomidine (DEX) is a selective...

  14. Isolated Unilateral Pulmonary Artery Agenesis complicated by Symptomatic Aspergilloma

    LENUS (Irish Health Repository)

    Daly, A

    2017-11-01

    Isolated unilateral pulmonary artery agenesis is a rare diagnosis. Poor blood flow to the lung parenchyma renders the tissue susceptible to opportunistic infections. We present the unusual case of isolated unilateral pulmonary artery agenesis complicated by aspergilloma. Management options and considerations are discussed.

  15. Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD

    DEFF Research Database (Denmark)

    Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas

    2016-01-01

    INTRODUCTION: Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. METHODS: 90...... perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation. TRIAL REGISTRATION NUMBER...

  16. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

    Directory of Open Access Journals (Sweden)

    Mehdi Peighambari

    2012-09-01

    Full Text Available Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  17. Apical Hypertrophic Cardiomyopathy in Association with Pulmonary Artery Hypertension

    OpenAIRE

    Peighambari, Mehdi; Parsaei, Mozghan; Sadeghpour, Anita; Alizadehasl, Azin

    2012-01-01

    Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM) diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  18. Unilateral Pulmonary Artery Aplasia in a Pregnant Patient

    Directory of Open Access Journals (Sweden)

    Chitra Lal

    2011-01-01

    Full Text Available Unilateral pulmonary artery aplasia is a rare anomaly. Case reports of this condition in pregnant patients are even more uncommon and the best approach to management of such patients is still unclear. We report a patient who presented with a history of dyspnea, chest pain, and hemoptysis. Imaging established the diagnosis in a newly pregnant female. Management of the pulmonary artery aplasia patient in pregnancy requires prospective evaluation of pulmonary hypertension.

  19. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris.

    Science.gov (United States)

    Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel

    2008-07-01

    Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.

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

    Science.gov (United States)

    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

  1. Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

    Science.gov (United States)

    Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M

    2000-07-27

    We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary

  2. Low-pressure pulmonary artery aneurysm presenting with pulmonary embolism: a case series

    Directory of Open Access Journals (Sweden)

    Papoulidis Pavlos

    2011-04-01

    Full Text Available Abstract Introduction Pulmonary artery aneurysm is an uncommon disorder with severe complications. The diagnosis is often difficult, since the clinical manifestations are non-specific and the treatment is controversial, as the natural history of the disease is not completely understood. Case presentation We describe the cases of two patients with pulmonary artery aneurysms. The first patient was a 68-year-old Caucasian man with an idiopathic low-pressure pulmonary artery aneurysm together with a pulmonary embolism. The patient preferred a conservative approach and was stable at the 10-month follow-up visit after being placed on anti-coagulant treatment. The second patient was a 66-year-old Caucasian woman with a low-pressure pulmonary artery aneurysm also presented together with a pulmonary embolism. The aneurysm was secondary to pulmonary valve stenosis. She received anti-coagulants and, after stabilization, underwent percutaneous balloon valvuloplasty. Conclusion Pulmonary embolism may be the initial presentation of a low-pressure pulmonary artery aneurysm. No underlying cause for pulmonary embolism was found in either of our patients, suggesting a causal association with low-pressure pulmonary artery aneurysm.

  3. 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

  4. Exercise Intolerance in Pulmonary Arterial Hypertension

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    Robin M. Fowler

    2012-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research.

  5. 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.

  6. Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery

    Directory of Open Access Journals (Sweden)

    Venkat Gangadharan MD

    2017-01-01

    Full Text Available A 36-year-old woman was seen with complaints of exertional chest pain and shortness of breath. Her medical history included atrial fibrillation and diabetes. Physical examination was unremarkable except for an irregular cardiac rhythm. Myocardial perfusion imaging revealed the presence of a large area of infarction involving the entire anterior and apical walls and part of the anteroseptal wall with minimal periinfarct ischemia. Computed tomography coronary angiogram revealed an anomalous left main coronary artery arising from the main pulmonary artery. Right and left heart catheterizations demonstrated moderate pulmonary hypertension with a slight step-up in oxygen saturation between the right ventricle and main pulmonary artery. Coronary angiography showed a large tortuous right coronary artery with collaterals to the left anterior descending artery that drained into the main pulmonary artery. She was referred for surgery. This case demonstrates a rare coronary artery anomaly in an adult where survival is dependent on collateral circulation.

  7. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    Science.gov (United States)

    Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

    2008-03-01

    Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

  8. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    Science.gov (United States)

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-12-01

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells (ECs) express hemoglobin (Hb) α to control nitric oxide (NO) diffusion, but the role of this system in pulmonary circulation has not been evaluated. We hypothesized that up-regulation of Hb α in pulmonary ECs contributes to NO depletion and pulmonary vascular dysfunction in pulmonary hypertension. Primary distal pulmonary arterial vascular smooth muscle cells, lung tissue sections from unused donor (control) and idiopathic pulmonary artery (PA) hypertension lungs, and rat and mouse models of SU5416/hypoxia-induced pulmonary hypertension (PH) were used. Immunohistochemical, immunocytochemical, and immunoblot analyses and transfection, infection, DNA synthesis, apoptosis, migration, cell count, and protein activity assays were performed in this study. Cocultures of human pulmonary microvascular ECs and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced PH were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of Hb α in pulmonary endothelium from humans and mice with PH compared with controls. In addition, we show up-regulation of Hb α in human pulmonary ECs cocultured with PA smooth muscle cells in hypoxia. We treated pulmonary ECs with a Hb α mimetic peptide that disrupts the association of Hb α with endothelial NO synthase, and found that cells treated with the peptide exhibited increased NO signaling compared with a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the Hb α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial Hb α functions as an endogenous scavenger of NO in the pulmonary endothelium

  9. [Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

    Science.gov (United States)

    Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

    2012-10-01

    To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

  10. 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

    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

  11. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Perros, Frédéric; Dorfmüller, Peter; Montani, David; Hammad, Hamida; Waelput, Wim; Girerd, Barbara; Raymond, Nicolas; Mercier, Olaf; Mussot, Sacha; Cohen-Kaminsky, Sylvia; Humbert, Marc; Lambrecht, Bart N

    2012-02-01

    Patients with idiopathic pulmonary arterial hypertension (IPAH) present circulating autoantibodies against vascular wall components. Pathogenic antibodies may be generated in tertiary (ectopic) lymphoid tissues (tLTs). To assess the frequency of tLTs in IPAH lungs, as compared with control subjects and flow-induced PAH in patients with Eisenmenger syndrome, and to identify local mechanisms responsible for their formation, perpetuation, and function. tLT composition and structure were studied by multiple immunostainings. Cytokine/chemokine and growth factor expression was quantified by real-time polymerase chain reaction and localized by immunofluorescence. The systemic mark of pulmonary lymphoid neogenesis was investigated by flow cytometry analyses of circulating lymphocytes. As opposed to lungs from control subjects and patients with Eisenmenger syndrome, IPAH lungs contained perivascular tLTs, comprising B- and T-cell areas with high endothelial venules and dendritic cells. Lymphocyte survival factors, such as IL-7 and platelet-derived growth factor-A, were expressed in tLTs as well as the lymphorganogenic cytokines/chemokines, lymphotoxin-α/-β, CCL19, CCL20, CCL21, and CXCL13, which might explain the depletion of circulating CCR6(+) and CXCR5(+) lymphocytes. tLTs were connected with remodeled vessels via an ER-TR7(+) stromal network and supplied by lymphatic channels. The presence of germinal center centroblasts, follicular dendritic cells, activation-induced cytidine deaminase, and IL-21(+)PD1(+) follicular helper T cells in tLTs together with CD138(+) plasma cell accumulation around remodeled vessels in areas of immunoglobulin deposition argued for local immunoglobulin class switching and ongoing production. We highlight the main features of lymphoid neogenesis specifically in the lungs of patients with IPAH, providing new evidence of immunological mechanisms in this severe condition.

  12. Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters

    OpenAIRE

    Yang Ting; Xu Dan; An Jin; He Guang-Ming; Chen Ya-Juan; Chen Lei; Ning Yun-Ye; Zhang Shang-Fu; Han Su-Xia; Wang Tao; Zhang Xiao-Hong; Wen Fu-Qiang

    2010-01-01

    Abstract Background Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-β1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Methods Hamsters were exposed ...

  13. Repair of congenital heart defects associated with single pulmonary artery.

    Science.gov (United States)

    Bockeria, Leo A; Makhachev, Osman A; Khiriev, Titalav Kh; Podzolkov, Vladimir P; Zelenikin, Mikhail A; Kim, Aleksey I; Zaets, Sergey B

    2015-02-01

    Experience with complete repair of congenital heart defects associated with unilateral absence of a pulmonary artery is limited. The aim of this retrospective study was to present our surgical experience of this complex category of patients, to analyze immediate results of surgical interventions, and to suggest a rational surgical strategy. Of 37 patients with a single pulmonary artery who underwent complete repair of associated heart defects, the left or right pulmonary artery was absent in 32 and 5, respectively. The most frequent heart defects were tetralogy of Fallot (n = 25) and ventricular septal defect (n = 8). The median age of these patients was 7.1 years. Preoperative examinations included echocardiography, cardiac catheterization and angiocardiography, with quantitative assessment of the single pulmonary artery. In-hospital parameters of surgical outcome were analyzed. Recorded hospital mortality was 2.7% (1/37). The single death was in a patient with tetralogy of Fallot, agenesis of the left pulmonary artery, and a small diameter of the contralateral pulmonary artery (Nakata index 174 mm(2)·m(-2)). The right-to-left ventricular systolic pressure ratio after complete tetralogy of Fallot repair in patients who survived the operation was 0.58 ± 0.11. Complete repair of congenital heart defects in patients with unilateral absence of a pulmonary artery is associated with a relatively low risk. If the hilar artery is of adequate size, surgical intervention should attempt restoration of the communication between the disconnected hilar artery and the pulmonary trunk, in addition to repairing the heart defects. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Pathophysiology and clinical implications of pulmonary arterial enlargement in COPD

    Directory of Open Access Journals (Sweden)

    Wells JM

    2013-10-01

    Full Text Available J Michael Wells, Mark T Dransfield Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama Birmingham and the Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA Abstract: Chronic obstructive pulmonary disease (COPD is a complex condition defined by progressive airflow limitation in response to noxious stimuli, inflammation, and vascular changes. COPD exacerbations are critical events in the natural history of the disease, accounting for the majority of disease burden, cost, and mortality. Pulmonary vascular disease is an important risk factor for disease progression and exacerbation risk. Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A ratio >1, has been evaluated as a marker of pulmonary vascular disease. The PA:A ratio can be measured reliably independent of electrocardiographic gating or the use of contrast, and in healthy patients a PA:A ratio >0.9 is considered to be abnormal. The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease. In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events. Future studies should be aimed at determining the stability of the metric over time and evaluating the utility of the PA:A ratio in guiding specific therapies. Keywords: pulmonary artery enlargement, aorta, ratio, pulmonary hypertension, chronic obstructive pulmonary disease, computed tomography

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

    Science.gov (United States)

    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.

  16. Selexipag for the Treatment of Pulmonary Arterial Hypertension

    DEFF Research Database (Denmark)

    Sitbon, Olivier; Channick, Richard; Chin, Kelly M

    2015-01-01

    BACKGROUND: In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension. METHODS: In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned 1156...... patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin......-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period (defined for each patient as 7 days after the date of the last intake of selexipag...

  17. Long term combination treatment for severe idiopathic pulmonary arterial hypertension

    Science.gov (United States)

    Affuso, Flora; Cirillo, Plinio; Ruvolo, Antonio; Carlomagno, Guido; Fazio, Serafino

    2010-01-01

    We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event. PMID:21160759

  18. Idiopathic pulmonary artery aneurysm treated with surgical correction and concomitant coronary artery bypass grafting.

    Science.gov (United States)

    Arnaoutakis, George; Nwakanma, Lois; Conte, John

    2009-07-01

    Idiopathic pulmonary artery aneurysm is a rare clinical entity, and therefore the natural course and clinical management are not well established. We present the case of an elderly woman with a symptomatic idiopathic pulmonary artery aneurysm who underwent surgical repair along with simultaneous coronary artery bypass grafting. With long-term follow-up presented in this report, we describe the safety and durability of surgical repair.

  19. Impaired Pulmonary Arterial Vasoconstriction and Nitric Oxide-Mediated Relaxation Underlie Severe Pulmonary Hypertension in Sugen-Hypoxia Rat Model.

    Science.gov (United States)

    Christou, Helen; Hudalla, Hannes; Michael, Zoe; Filatava, Evgenia; Li, Jun; Zhu, Minglin; Possomato-Vieira, Jose; Dias-Junior, Carlos; Kourembanas, Stella; Khalil, Raouf A

    2017-12-06

    Pulmonary vasoreactivity could determine the responsiveness to vasodilators and in turn the prognosis of pulmonary hypertension (PH). We hypothesized that pulmonary vasoreactivity is impaired, and examined the underlying mechanisms, in the sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were injected with sugen (20 mg/kg sc) and exposed to hypoxia (9% O2) for 3 weeks followed by 4 weeks in normoxia (Su/Hx), or treated with sugen alone (Su) or hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was assessed for right ventricular hypertrophy (Fulton's Index), the pulmonary artery, aorta and mesenteric arteries were isolated for vascular function studies, and contractile markers were measured in pulmonary artery using quantitative PCR. Other rats were used for morphometric analysis of pulmonary vascular remodeling. Right ventricular systolic pressure and Fulton's Index were higher in Su/Hx vs Su, Hx and Nx rats. Pulmonary vascular remodeling was more prominent in Su/Hx vs Nx rats. In pulmonary artery rings, contraction to high KCl (96 mM) was less in Su/Hx vs Nx and Su, and phenylephrine-induced contraction was reduced in Su/Hx vs Nx, Hx and Su. Acetylcholine (ACh)-induced relaxation was less in Su/Hx vs Nx and Hx, suggesting reduced endothelium-dependent vasodilation. ACh relaxation was inhibited by NOS and guanylate cyclase blockade in all groups, suggesting a role of the NO-cGMP pathway. Nitrate/nitrite production in response to ACh was less in Su/Hx vs Nx, supporting reduced endothelial NO production. Sodium nitroprusside (10-8 M) caused less relaxation in Su/Hx vs Nx, Hx and Su, suggesting decreased responsiveness of vascular smooth muscle (VSM) to vasodilators. Neither contraction nor relaxation differed in the aorta or mesenteric arteries of all groups. PCR analysis showed decreased expression of contractile markers in pulmonary artery of Su/Hx vs Nx. The reduced responsiveness to vasoconstrictors and NO

  20. Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

    Science.gov (United States)

    Shah, Shilpa; Szmuszkovicz, Jacqueline R.

    2017-01-01

    The perioperative period is an extremely tenuous time for the pediatric patient with pulmonary arterial hypertension. This article will discuss a multidisciplinary approach to preoperative planning, the importance of early identification of pulmonary hypertensive crises, and practical strategies for postoperative management for this unique group of children. PMID:29064445

  1. Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

    Directory of Open Access Journals (Sweden)

    Shilpa Shah

    2017-10-01

    Full Text Available The perioperative period is an extremely tenuous time for the pediatric patient with pulmonary arterial hypertension. This article will discuss a multidisciplinary approach to preoperative planning, the importance of early identification of pulmonary hypertensive crises, and practical strategies for postoperative management for this unique group of children.

  2. Phosphodiesterase 10A upregulation contributes to pulmonary arterial hypertension

    OpenAIRE

    Tian, Xia

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease defined by an elevation of pulmonary vascular resistance due to sustained vessel contraction and enhanced vascular remodeling. The abnormal tone and remodeling in the pulmonary vasculature are believed to be related, at least in part, to the decrease of cyclic nucleotide levels that are controlled by cyclic nucleotide phosphodiesterases (PDEs). PDEs, of which 11 families have been identified, maintain homeostasis...

  3. A PROSPECTIVE STUDY OF PULMONARY ARTERIAL HYPERTENSION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASES

    Directory of Open Access Journals (Sweden)

    Saptanaga Kumar

    2015-04-01

    Full Text Available BACKGROUND : Chronic obstructive pulmonary disease (COPD is a heterogeneous, multisystem disease with complexities that extend far beyond airway obstruction. OBJECTIVES : The purpose of this prospective study is to determine pulmonary arterial hypertension in chronic obstructi ve pulmonary disease non - invasively. METHODS : In this descriptive, prospective, observational, cross sectional study, all patients who presented to the department of Medicine and Respiratory medicine, during this study period of 12 months from January 2013 - December 2014 in Chennai were included. RESULTS : Total number of males in the study is 90(90%, females in the study is 10 (10%. Number of patients in the age group 25 - 35years was 06 (6%, 36 - 45years was 38(38%, 46 - 55 years was 30(30, number of patie nts in 56 - 65 years was 14 (14 and number of patients in the age group 66 - 75 years was 12(12. total number of males smoking in the study is 55(61.11% and total number of non - smokers were 35(38.88, total number of female smoking in the study is 1(10% an d total number of non - smokers were 9(90%. Pulmonary arterial systolic pressure in present study, Mild pulmonary arterial hypertension was seen in 26(26%, Moderate pulmonary arterial hypertension was seen in 54(54%, Severe pulmonary arterial hypertension was seen in 20(20%. CONCLUSION : This study shows the prevalence of pulmonary arterial hypertension in COPD patients.

  4. Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions

    NARCIS (Netherlands)

    van Albada, Mirjam E.; Bartelds, Beatrijs; Wijnberg, Hans; Mohaupt, Saffloer; Dickinson, Michael G.; Schoemaker, Regien G.; Kooi, Krista; Gerbens, Frans; Berger, Rolf M. F.

    Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key

  5. Optimal management of severe pulmonary arterial hypertension.

    Science.gov (United States)

    Sitbon, O; Simonneau, G

    2011-12-01

    Over the past decade, awareness among the medical profession of pulmonary arterial hypertension (PAH) being a treatable disease has increased. Despite this, approximately one-fifth of newly diagnosed patients are classified as being in the most severely compromised functional class (i.e. New York Health Association/World Health Organization functional class (NYHA/WHO FC) IV). The prognosis for patients in NYHA/WHO FC IV is poor, with 3-yr survival being around 40%, even with treatment. Poor prognosis coupled with severe functional impairment means it is vital that these patients receive optimal treatment. There are also subgroups of patients, who, although classified as NYHA/WHO FC III, may actually be severely haemodynamically compromised and at risk of rapid deterioration. Such subgroups include patients with PAH associated with systemic sclerosis or certain heritable mutations. These patients should be considered as being at the more severe end of the disease spectrum. In this article we will discuss the optimal management of patients with severe PAH. This includes newly emerging evidence from small-scale, open-label studies that use upfront combination therapy with intravenous epoprostenol plus oral PAH-specific drugs. We also review treatment strategies that may offer clinical benefits to patients with more severe PAH.

  6. How prostacyclin therapy improves right ventricular function in pulmonary arterial hypertension

    OpenAIRE

    Vanderpool, Rebecca R.; Desai, Ankit A.; Knapp, Shannon M.; Simon, Marc A.; Abidov, Aiden; Yuan, Jason X.-J.; Garcia, Joe G. N.; Hansen, Lillian M.; Knoper, Steven R.; Naeije, Robert; Rischard, Franz P.

    2017-01-01

    Within recent years, right ventricular (RV) function has been recognised as a major determinant of outcome in pulmonary arterial hypertension (PAH) [1, 2]. Clinical [3] and in vitro experimental [4, 5] data suggest that prostacyclins, the treatment of choice for most severely ill PAH patients [6], might have a positive inotropic effect on RV function, and reduce pulmonary vascular resistance (PVR). Nevertheless, inotropic effects are difficult to demonstrate in vivo, as ventricular contractil...

  7. Aortic homograft for pulmonary artery augmentation in single lung transplantation.

    Science.gov (United States)

    Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda

    2005-06-01

    We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.

  8. A Novel Vascular Homing Peptide Strategy to Selectively Enhance Pulmonary Drug Efficacy in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Toba, Michie; Alzoubi, Abdallah; O’Neill, Kealan; Abe, Kohtaro; Urakami, Takeo; Komatsu, Masanobu; Alvarez, Diego; Järvinen, Tero A.H.; Mann, David; Ruoslahti, Erkki; McMurtry, Ivan F.; Oka, Masahiko

    2015-01-01

    A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH. PMID:24401613

  9. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension

    Science.gov (United States)

    De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe

    2012-01-01

    Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525

  10. Small pulmonary artery defects are not reliable indicators of pulmonary embolism.

    Science.gov (United States)

    Miller, Wallace T; Marinari, Lawrence A; Barbosa, Eduardo; Litt, Harold I; Schmitt, James E; Mahne, Anton; Lee, Victor; Akers, Scott R

    2015-07-01

    To evaluate the rate of agreement of pulmonary embolism diagnosis in computed tomography (CT) pulmonary angiogram studies and to evaluate the rate of inaccurate interpretations in the community hospital setting. Using the keywords "pulmonary embolism/embolus/emboli," the radiology information system was searched for CT pulmonary angiograms performed over a 3-year period at three U.S. community hospitals. Studies containing probable or definite pulmonary emboli were independently reviewed by four subspecialty thoracic radiologists. Agreement about the presence of pulmonary embolism progressively decreased with decreasing diameter of pulmonary vascular lesions (P pulmonary embolism of subsegmental lesions (P pulmonary embolism diagnosis of subsegmental and/or small pulmonary arterial defects. The probability of a false-positive diagnosis and indeterminate examinations progressively increased with: (1) more peripheral location of the lesion, (2) decreased size (short-axis diameter) of the lesion, and (3) diminishing quality of the CT examination. Forty-eight of 177 (27%) of subsegmental vascular defects identified by community radiologists were deemed indeterminate, and 27 of 177 (15%) of subsegmental vascular defects were judged to be false positive for pulmonary embolism by the consensus diagnosis. Fifty-four of 274 (20%) vascular defects with short axis less than 6 mm were indeterminate for pulmonary embolism, and 37 of 274 (14%) of vascular defects with short axis less than 6 mm were false positive for pulmonary embolism. Eleven of 13 (85%) of vascular lesions identified as pulmonary emboli on the lowest-quality CT examinations were false positive or indeterminate for pulmonary embolism. False-positive examinations were most often due to respiratory motion artifact (19/38, 50%). There is relatively poor interobserver agreement for subsegmental and/or small pulmonary artery defects, especially in CT pulmonary angiograms degraded by technical artifacts. These

  11. Computational simulation of postoperative pulmonary flow distribution in Alagille patients with peripheral pulmonary artery stenosis.

    Science.gov (United States)

    Yang, Weiguang; Hanley, Frank L; Chan, Frandics P; Marsden, Alison L; Vignon-Clementel, Irene E; Feinstein, Jeffrey A

    2017-12-01

    Up to 90% of individuals with Alagille syndrome have congenital heart diseases. Peripheral pulmonary artery stenosis (PPS), resulting in right ventricular hypertension and pulmonary flow disparity, is one of the most common abnormalities, yet the hemodynamic effects are ill-defined, and optimal patient management and treatment strategies are not well established. The purpose of this pilot study is to use recently refined computational simulation in the setting of multiple surgical strategies, to examine the influence of pulmonary artery reconstruction on hemodynamics in this population. Based on computed tomography angiography and cardiac catheterization data, preoperative pulmonary artery models were constructed for 4 patients with Alagille syndrome with PPS (all male, age range: 0.6-2.9 years), and flow simulations with deformable walls were performed. Surgeon directed virtual surgery, mimicking the surgical procedure, was then performed to derive postoperative models. Postoperative simulation-derived hemodynamics and blood flow distribution were then compared with the clinical results. Simulations confirmed substantial resistance, resulting from preoperative severe ostial stenoses, and the use of newly developed adaptive outflow boundary conditions led to excellent agreement with in vivo measurements. Relief of PPS decreased pulmonary artery pressures and improved pulmonary flow distribution both in vivo and in silico with good correlation. Using adaptive outflow boundary conditions, computational simulations can estimate postoperative overall pulmonary flow distribution in patients with Alagille syndrome after pulmonary artery reconstruction. Obstruction relief along with pulmonary artery vasodilation determines postoperative pulmonary flow distribution and newer methods can incorporate these physiologic changes. Evolving blood flow simulations may be useful in surgical or transcatheter planning and in understanding the complex interplay among various

  12. [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.

  13. Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension

    NARCIS (Netherlands)

    van der Feen, Diederik E; Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Sietsma, Hannie; Lévy, Marilyne; Berger, Rolf M F

    BACKGROUND: Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated

  14. 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.

  15. Moyamoya Disease with Peripheral Pulmonary Artery Stenoses and Coronary Artery Fistulae

    Directory of Open Access Journals (Sweden)

    Lindsay Reardon

    2009-01-01

    Full Text Available Moyamoya is a progressive disorder of the cerebral vasculature. Our report describes a rare case of Moyamoya disease with distal peripheral pulmonary artery stenoses and coronary fistulae in a 12-year-old Caucasian female patient.

  16. Hybrid Melody pulmonary valve replacement in an adult with severe pulmonary hypertension and pulmonary artery aneurysm.

    Science.gov (United States)

    Derk, Gwendolyn; Laks, Hillel; Aboulhosn, Jamil

    2013-11-01

    A 48-year-old female with D-TGA, ventricular septal defect (VSD), pulmonary stenosis, pulmonary hypertension (PAH), and total anomalous pulmonary venous connection underwent hybrid intervention for a pulmonary artery (PA) aneurysm and replacement of a dysfunctional pulmonary valve (PV). She underwent a hemi-Mustard procedure at 9 years of age but remained cyanotic. She developed atrial fibrillation, heart failure, and functional decline at 43 years of age. A chest CT demonstrated a 6 cm PA aneurysm that upon re-imaging at 48 years had increased to 11 cm. A catheterization procedure revealed severe PS, PR, residual VSD, severe PAH with a pulmonary vascular resistance of 30 Wood units. She was evaluated and turned down for heart-lung transplantation at another institution. She was subsequently referred to our institution for heart-lung transplantation but was felt to be at unacceptably high risk given the complexity of her anatomy, imaging suggesting liver cirrhosis and liver biopsy with extensive fibrosis. After extensive discussion of risk and benefits, the patient agreed to proceed with a hybrid intervention, consisting of surgical aneurysm resection/PA repair, tricuspid valve repair; PV replacement with a Melody valve, and VSD closure. There were no complications and she was discharged home within 2 weeks. Six months post procedure, she is not on oxygen, her resting room air saturation is 94%, and echocardiography shows stable Melody valve function. This case highlights the utility of a hybrid approach in the treatment of an adult with complex congenital heart disease, heart failure and severe PAH, considered at the highest risk for adverse surgical outcomes. The short-term efficacy of the Melody valve in severe PAH is reassuring. Copyright © 2013 Wiley Periodicals, Inc.

  17. Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced pulmonary hypertension

    NARCIS (Netherlands)

    van Suylen, R. J.; Smits, J. F.; Daemen, M. J.

    1998-01-01

    In the present study we analyzed structural characteristics of muscular pulmonary arteries and arterioles in two classic models of pulmonary hypertension, the rat hypoxia and monocrotaline models. We hypothesized that an increase in medial cross-sectional area would result in reduction of the lumen

  18. [Arterial rigidity in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Karoli, N A; Dolishniaia, G R; Rebrov, A P

    2012-01-01

    The aim of this open study was to estimate arterial rigidity in patients with chronic obstructive pulmonary disease (COPD). It included 105 patients above 40 years of age. Exclusion criteria were clinical signs of CHD, peripheral atherosclerosis, and other severe chronic diseases in the exacerbation phase. The control group was comprised of 27 practically healthy volunteers. The arterial fluid was detected using a Tensioclinic arteriograph (Tensiomed, Hungary). Arterial rigidity was estimated in patients of two age groups (below and above 60 years) with COPD of different severity The results suggest the development of arterial wall lesions in proportion to the patients' age and COPD severity. It was shown that excessive arterial rigidity and accelerated pulse wave reflection (increased speed of pulse wave propagation and augmentation index) exert significant influence on the elevation of central arterial pressure. Enhanced rigidity of the arterial wall being a cardiovascular risk factor further prospective studies are needed.

  19. Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Caro-Dominguez, Pablo; Manson, David E. [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada); Compton, Gregory [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada); Epworth Hospital, Epworth Medical Imaging, Richmond, VIC (Australia); Humpl, Tilman [University of Toronto, Division of Cardiology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON (Canada)

    2016-09-15

    The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children. (orig.)

  20. Changes in pulmonary artery pressure affect survival differently in lung transplant recipients who have pulmonary hypertension or chronic obstructive pulmonary disease.

    Science.gov (United States)

    O'Keefe, Kathryn L; Kilic, Ahmet; Pope-Harman, Amy; Hayes, Don; Kirkby, Stephen; Higgins, Robert S D; Whitson, Bryan A

    2014-08-01

    Pulmonary hypertension and right ventricular dysfunction can complicate lung transplant. Pulmonary artery pressures affect outcome are uncertain during wait list. We evaluated changes in wait list pulmonary artery pressures on survival after lung transplant. We queried the United Network for Organ Sharing/Standard Transplant Analysis and Research registry from 1987 to 2012 for all lung transplants. Recipients with unique pulmonary artery pressure measurements upon listing and transplant were included. Mean pulmonary artery pressure was rated as increased (increase > 5 mm Hg), decreased (decrease > 5 mm Hg), or unchanged (variation pulmonary artery pressure during the listing period (P ≤ .0001). In recipients with chronic obstructive pulmonary disease, survival was poorer when mean pulmonary artery pressure was increased than decreased (P ≤ .03). In recipients with primary pulmonary hypertension, survival was poorer when mean pulmonary artery pressure was decreased than increased (P ≤ .02). Proportional hazards analysis showed that increases in mean pulmonary artery pressure independently affected survival (hazard ratio, 0.78; 95% confidence interval, 0.62-0.96). Although the mechanism is unknown, an increase in mean pulmonary artery pressure in patients with chronic obstructive pulmonary disease is associated with poorer survival after lung transplant. In contrast, patients with primary pulmonary hypertension with decreased mean pulmonary artery pressure have poorer survival after lung transplant. In patients with primary pulmonary hypertension, changes in pulmonary artery pressure may be a surrogate for a failing right ventricular function. In chronic obstructive pulmonary disease, the change in pressure suggests an undetermined progressive process. Further study of right ventricular function is warranted to determine the effects of changes in pulmonary artery pressure on lung transplant recipients.

  1. Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnosis with CT Angiography

    Directory of Open Access Journals (Sweden)

    Guray Oncel

    2013-01-01

    Full Text Available Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA is a rare congenital anomaly. It is associated with early infant mortality and sudden death in adults. Traditionally, ALCAPA has been diagnosed by angiography or autopsy; however, the development of cardiac computed tomography (CT and magnetic resonance imaging (MRI has allowed noninvasive evaluation of the coronary anatomy by direct visualization of the origin of the left coronary artery (LCA from the pulmonary artery. We report a case of 10-year-old girl who has been on follow up for dilated cardiomyopathy for 4 years. The definitive diagnosis of ALCAPA is reached by multislice computed tomography (MSCT. The MSCT scan showed an anomalous origin of LCA from the pulmonary trunk, with a tortuous and dilated right coronary artery and right-to-left collateralization. Consequently, the patient was successfully treated with surgery.

  2. Pulmonary arterial lesions in explanted lungs after transplantation correlate with severity of pulmonary hypertension in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Carlsen, Jørn; Hasseriis Andersen, Kasper; Boesgaard, Søren

    2013-01-01

    BACKGROUND: Pulmonary vascular findings are largely unreported in end-stage chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary vascular lesions in explanted lungs from 70 patients with COPD/emphysema or α-1-antitrypsin deficiency were analyzed retrospectively. Patients were stratified...... by the presence and severity of pulmonary hypertension (PH) assessed by right-heart catheterization in 3 hemodynamically distinct groups: (1) non-PH (mean pulmonary arterial pressure [mPAP]50 mm Hg; median HE Grade 4 (range 3-6), with generalized arterial dilatation and plexiform lesions. CONCLUSIONS: The extent...... of pulmonary vascular lesions in COPD correlate with the severity of PH. Morphologic lesions similar to those characteristic of IPAH can be observed as PH in COPD progresses to levels characteristic of IPAH....

  3. Assembly of a Pulmonary Artery Pressure Sensor System

    Directory of Open Access Journals (Sweden)

    J. Müntjes

    2010-01-01

    Full Text Available This paper presents an implantable system for telemonitoring the intravascular pressure in the pulmonary artery. By implanting a catheter-bound pressure and temperature sensor into the pulmonary artery, it is possible to monitor the actual value and the time variations of the intravascular pressure with a frequency of 128 Hz. Thus hospitalization of patients suffering from heart insufficiency can be avoided by early changes in therapy.Preliminary in vivo experiments have been conducted to verify the fixation mechanism and the positioning of the sensor at the right place in the pulmonary artery. It was shown that the proposed fixation mechanism and the packaging of the sensor promise to be stable.

  4. Sirtuin 1 regulates pulmonary artery smooth muscle cell proliferation: role in pulmonary arterial hypertension.

    Science.gov (United States)

    Zurlo, Giada; Piquereau, Jérôme; Moulin, Maryline; Pires Da Silva, Julie; Gressette, Mélanie; Ranchoux, Benoît; Garnier, Anne; Ventura-Clapier, Renée; Fadel, Elie; Humbert, Marc; Lemaire, Christophe; Perros, Frédéric; Veksler, Vladimir

    2018-01-24

    Energy metabolism shift from oxidative phosphorylation toward glycolysis in pulmonary artery smooth muscle cells (PASMCs) is suggested to be involved in their hyperproliferation in pulmonary arterial hypertension (PAH). Here, we studied the role of the deacetylase sirtuin1 (SIRT1) in energy metabolism regulation in PASMCs via various pathways including activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), master regulator of mitochondrial biogenesis. Contents of PGC-1α and its downstream targets as well as markers of mitochondrial mass (voltage-dependent anion channel and citrate synthase) were diminished in human PAH PASMCs. These cells and platelet-derived growth factor-stimulated rat PASMCs demonstrated a shift in cellular acetylated/deacetylated state, as evidenced by the increase of the acetylated forms of SIRT1 targets: histone H1 and Forkhead box protein O1. Rat and human PASMC proliferation was potentiated by SIRT1 pharmacological inhibition or specific downregulation via short-interfering RNA. Moreover, after chronic hypoxia exposure, SIRT1 inducible knock out mice displayed a more intense vascular remodeling compared with their control littermates, which was associated with an increase in right ventricle pressure and hypertrophy. SIRT1 activator Stac-3 decreased the acetylation of histone H1 and Forkhead box protein O1 and strongly inhibited rat and human PASMC proliferation without affecting cell mortality. This effect was associated with the activation of mitochondrial biogenesis evidenced by higher expression of mitochondrial markers and downstream targets of PGC-1α. Altered acetylation/deacetylation balance as the result of SIRT1 inactivation is involved in the pathogenesis of PAH, and this enzyme could be a promising therapeutic target for PAH treatment.

  5. Treprostinil in advanced experimental pulmonary hypertension : Beneficial outcome without reversed pulmonary vascular remodeling

    NARCIS (Netherlands)

    van Albada, Mirjam E.; van Veghel, Richard; Cromme-Dijkhuis, Adri H.; Schoemaker, Regien G.; Berger, Ro F. M. E.

    2006-01-01

    Introduction: Beneficial effects of treprostmil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown. Methods:

  6. Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

    Science.gov (United States)

    Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

    2015-04-01

    Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

    Directory of Open Access Journals (Sweden)

    Cogolludo Angel

    2011-04-01

    Full Text Available Abstract Background Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat. Methods Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique. Results Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W. Conclusions In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.

  8. Efficacy of pulmonary artery banding in patients with uneventricular defects

    Directory of Open Access Journals (Sweden)

    Ю. С. Синельников

    2015-10-01

    Full Text Available Long-term results where evaluated for different methods of pulmonary artery banding (PAB in 25 patients with univentricular congenital heart defects with used three methods. Hospital mortality was 8%. Second stage palliation was performed in 61% of patients. More tight PA banding in patients with univentriclar gave opportunity to perform 2nd stage of operation in 100% of patients, decrease complications and mortality rate, modify pulmonary circulation effectively.

  9. Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists

    Directory of Open Access Journals (Sweden)

    Gregory James Skinner

    2017-09-01

    Full Text Available There is a growing awareness of the role that increased pulmonary vascular resistance (PVR plays in many pathologies; therefore, assessment of pulmonary artery pressure (PAP is an increasingly requested investigation in the critical care environment. This article will go through the basic concepts regarding PAP and PVR, then will go on to outline the various echocardiographic parameters which are used to assess them. Finally, an outline of how to undertake this assessment will be presented.

  10. Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists.

    Science.gov (United States)

    Skinner, Gregory James

    2017-01-01

    There is a growing awareness of the role that increased pulmonary vascular resistance (PVR) plays in many pathologies; therefore, assessment of pulmonary artery pressure (PAP) is an increasingly requested investigation in the critical care environment. This article will go through the basic concepts regarding PAP and PVR, then will go on to outline the various echocardiographic parameters which are used to assess them. Finally, an outline of how to undertake this assessment will be presented.

  11. Congenital arteriovenous fistula between the internal mammary artery and the pulmonary artery

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); H. van Meurs-van Woezik

    1984-01-01

    textabstractThis is the fourth reported case of congenital arteriovenous fistula between the internal mammary artery and pulmonary artery. Precise and complete diagnostic evaluation is required to localize, delineate and appreciate the haemodynamic significance of this type of arteriovenous shunt. A

  12. Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Prevalence and Predictors.

    Science.gov (United States)

    Pérez-Peñate, Gregorio Miguel; Rúa-Figueroa, Iñigo; Juliá-Serdá, Gabriel; León-Marrero, Fernándo; García-Quintana, Antonio; Ortega-Trujillo, José Ramón; Erausquin-Arruabarrena, Celia; Rodríguez-Lozano, Carlos; Cabrera-Navarro, Pedro; Ojeda-Betancor, Nazario; Gómez-Sánchez, Miguel Ángel

    2016-02-01

    Pulmonary arterial hypertension (PAH) prevalence has been reported to be between 0.5% and 17% in systemic lupus erythematosus (SLE). This study assessed PAH prevalence and predictors in an SLE cohort. The Borg dyspnea scale, DLCO, N-terminal pro-brain natriuretic peptide (NT-proBNP), and Doppler echocardiographic (DE) were performed. An echocardiographic Doppler exercise test was conducted in selected patients. When DE systolic pulmonary arterial pressure was ≥ 45 mmHg or increased during exercise > 20 mmHg, a right heart catheterization was performed. Hemodynamic during exercise was measured if rest mean pulmonary arterial pressure was exercise-induced pulmonary artery pressure increase (4 with occult left diastolic dysfunction). These patients had significantly more dyspnea, higher NT-proBNP, and lower DLCO. These data confirm the low prevalence of PAH in SLE. In our cohort, occult left ventricular diastolic dysfunction was a frequent diagnosis of unexplained dyspnea. Dyspnea, DLCO, and NT-proBNP could be predictors of pulmonary hypertension in patients with SLE.

  13. Potassium currents in cultured human pulmonary arterial smooth muscle cells.

    Science.gov (United States)

    Peng, W; Karwande, S V; Hoidal, J R; Farrukh, I S

    1996-04-01

    In this study, using whole cell and single-channel configurations of the patch-clamp technique, we characterized K+ currents (IK) in cultured human pulmonary arterial smooth muscle cells. The net whole cell outward membrane current (IKo) was activated at potentials positive to -60 mV. One component of IKo, IK(dr), was inhibited by 4-aminopyridine (4-AP) and high concentrations of tetraethylammonium (TEA) but was Ca2+ and charybdotoxin (CTX) insensitive. The other component of IKo, IK(Ca), was voltage and Ca2+ dependent and was inhibited by CTX and low concentrations of TEA. Activation of IKo in single-channel recordings was voltage dependent and demonstrated a high-conductance channel (245 +/- 2 pS) that was Ca2+ and CTX sensitive [IK(Ca)] and a low-conductance channel (109 +/- 2 pS) that was inhibited by 4-AP [IK(dr)] but was insensitive to low concentrations of TEA or to an increase in intracellular [Ca2+]. In isolated pulmonary arterial rings, TEA and 4-AP caused an additive increase in arterial tension. To our knowledge these data provide the first characterization of the IK in human pulmonary arterial smooth muscle cells and indicate that IK(Ca) and IK(dr) play an important role in maintaining pulmonary vascular tone. The data confirm previous observations in pulmonary smooth muscle cells of animal models.

  14. Fetal Isolated Anomalous Origin of Right Pulmonary Artery from Aorta

    Directory of Open Access Journals (Sweden)

    Shi Zeng

    2015-04-01

    Full Text Available The anomalous origin of a branch pulmonary artery from the aorta (AOPA is characterized by the anomalous origin of one of the branch pulmonary arteries (PA from the ascending aorta and a normal origin of the other PA from main PA. AOPA is an extremely rare cardiac malformation. Few studies have reported fetal anomalous origin of PA from aorta with other malformation. We report a case of isolated distal anomalous origin of the right PA from the aorta that was diagnosed by fetal echocardiography at 25 weeks' of gestation. Tracing the course of PA branches is important to make diagnosis.

  15. Fetal Isolated Anomalous Origin of Right Pulmonary Artery from Aorta.

    Science.gov (United States)

    Zeng, Shi; Zhou, Qichang; Zhou, Jiawei; Peng, Qinghai

    2015-04-01

    The anomalous origin of a branch pulmonary artery from the aorta (AOPA) is characterized by the anomalous origin of one of the branch pulmonary arteries (PA) from the ascending aorta and a normal origin of the other PA from main PA. AOPA is an extremely rare cardiac malformation. Few studies have reported fetal anomalous origin of PA from aorta with other malformation. We report a case of isolated distal anomalous origin of the right PA from the aorta that was diagnosed by fetal echocardiography at 25 weeks' of gestation. Tracing the course of PA branches is important to make diagnosis.

  16. Pulmonary artery catheter-directed thrombolysis for intermediate high risk acute pulmonary embolism

    Directory of Open Access Journals (Sweden)

    Abhijeet Singh

    2017-01-01

    Full Text Available A case of 60-year-old male with acute pulmonary embolism without hypotension but signs of right ventricular dysfunction and elevated cardiac biomarkers is reported in this study. The patient comes under intermediate high-risk category and was successfully thrombolysed with alteplase infused through pulmonary artery catheter. Catheter-directed thrombolysis (CDT can be considered as much safer and effective alternative to systemic thrombolysis in such patients with lower risk of bleeding. This novel bedside method of pulmonary artery CDT with the advantage of no radiation exposure and real time monitoring of pulmonary artery pressures as an end-point of thrombolysis can be utilized in the near future.

  17. Contrast Media Delivery in the Assessment of Anomalous Left Coronary Artery From the Pulmonary Artery.

    Science.gov (United States)

    Saade, Charbel; Al-Hamra, Salam; Al-Mohiy, Hussain; El-Merhi, Fadi

    2016-05-01

    A patient with a history of mitral valve prolapse and regurgitation that was corrected with a mitral ring repair 15 years earlier received a diagnosis of anomalous left coronary artery arising from the pulmonary artery and underwent repair. Coronary computed tomography angiography (CTA) was employed to image the patient before surgical intervention. Synchronizing contrast media administration to opacify the right coronary artery in the arterial phase and the left coronary artery in the venous phase required a test-bolus approach. Matching compromised cardiovascular dynamics with patient-specific contrast media administration protocols was improved considerably with the use of a test-bolus technique during electrocardiography-gated coronary CTA.

  18. Initial isolated Takayasu`s arteritis of the right pulmonary artery: MR appearance

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, G. [Department of Radiology, CHU Michallon, J Fourier University, Grenoble, F-38 043 Grenoble Cedex (France); Defaye, P. [Department of Cardiology, CHU Michallon, J Fourier University, Grenoble, F-38 043 Grenoble Cedex (France); Thony, F. [Department of Radiology, CHU Michallon, J Fourier University, Grenoble, F-38 043 Grenoble Cedex (France); Ranchoup, Y. [Department of Radiology, CHU Michallon, J Fourier University, Grenoble, F-38 043 Grenoble Cedex (France); Coulomb, M. [Department of Radiology, CHU Michallon, J Fourier University, Grenoble, F-38 043 Grenoble Cedex (France)

    1996-08-01

    Takayasu`s arteritis involves the pulmonary artery tree in more than 50 % of the cases. Initial isolated involvement of the pulmonary artery by Takayasu`s arteritis, however, is very rare. We report the case of a 34-year-old white woman who presented a clinical and radiographic pattern that mimicked an acute pulmonary embolism with pulmonary infarction. Pulmonary angiography showed stenosis lesions and occlusion of the right pulmonary artery tree. Magnetic resonance imaging demonstrated thickening of the pulmonary artery wall leading to the correct diagnosis. (orig.). With 3 figs.

  19. Anomalous left the pulmonary dilemma coronary artery artery from a ...

    African Journals Online (AJOL)

    a continuous murmur associated with angina-like attacks in older patients. Autopsy on these patients reveals a grossly dilated left coronary artery with viable anastomoses between the two coro- nary arteries. Finalll' sudden death is reported in 30% of adults with this anomaly.4, ,10 Characteristically, autopsy shows a large.

  20. ROCK2 mediates the proliferation of pulmonary arterial endothelial cells induced by hypoxia in the development of pulmonary arterial hypertension

    OpenAIRE

    Qiao, Feng; ZOU, ZHITIAN; Liu, Chunhui; Zhu, Xiaofeng; Wang, Xiaoqiang; Yang, Chengpeng; JIANG, TENGJIAO; Chen, Ying

    2016-01-01

    It has been reported that RhoA activation and Rho-kinase (ROCK) expression are increased in chronic hypoxic lungs, and the long-term inhibition of ROCK markedly improves the survival of patients with pulmonary arterial hypertension (PAH). However, whether Rho-kinase α (ROCK2) participates in regulation of the growth of pulmonary arterial endothelial cells (PAECs) remains unknown. The aim of the present study was to investigate the effect of hypoxia on the proliferation of PAECs and the role o...

  1. Late Posthemorrhagic Structural and Functional Changes in Pulmonary Circulation Arteries

    Directory of Open Access Journals (Sweden)

    S. A. Andreyeva

    2008-01-01

    Full Text Available Objective: to reveal the major regularities and mechanisms of morphological changes in the rat pulmonary circulation arteries in the late posthemorrhagic period and to compare them with age-related features of the vessels. Materials and methods: experiments to generate graduated hemorrhagic hypotension with the blood pressure being maintained at 40 mm Hg were carried out on young (5—6-month albino male Wistar rats. Throughout hypotension and 60 days after blood loss, the blood was tested to determine low and average molecular-weight substances by spectrophotometry and the pro- and antioxidative systems by chemiluminescence. Pulmonary circulation arteries were morphologically studied in young animals, rats in the late posthemorrhagic period and old (24—25-month rats. Results. Sixty-minute hemorrhagic hypotension leads to the development of endotoxemia and imbalance of the pro- and antioxidative systems, the signs of which are observed in the late periods (2 months after hypotension. At the same time, the posthemorrhagic period is marked by the significant pulmonary circulation arterial morphological changes comparable with their age-related alterations in old rat. This shows up mainly in the reorganization of a connective tissue component in the vascular wall: the elevated levels of individual collagen fibers, their structural changes, elastic medial membrane destruction and deformity. At the same time, there is a change in the morphometric parameters of vessels at all study stages while their lowered flow capacity is only characteristic for intraorgan arteries. Conclusion: The increased activity of free radical oxidation and endotoxemia may be believed to be one of the causes of morphological changes in pulmonary circulation arteries in the late posthemorrhagic period, which is similar to age-related vascular alterations. Key words: hemorrhagic hypotension, pulmonary circulation arteries, free radical oxidation, endotoxemia, remodeling, late

  2. Role of Bosentan in Pulmonary arterial hypertension | Saleh ...

    African Journals Online (AJOL)

    This review is aimed at sensitising the clinician to be more vigilant of pulmonary arterial hypertension and further emphasizing the role played by bosentan in its management. Bosentan, an oral non-specific endothelin-receptor antagonist with dual activity on both Endothelin A and Endothelin B receptors, has been shown to ...

  3. Changing demographics of pulmonary arterial hypertension in congenital heart disease

    NARCIS (Netherlands)

    Mulder, B. J. M.

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease (CHD). Without early surgical repair, around one-third of paediatric CHD patients develop significant PAH. Recent data from the Netherlands suggest that >4% of adult CHD patients have PAH, with higher rates

  4. Aneurysmal dilatation of the pulmonary artery trunk and its major ...

    African Journals Online (AJOL)

    She was admitted for cough and dyspnea of acute onset without fever or chest pain. The patient was in respiratory distress, afebrile and ... The causes are dominated by infectious diseases, inflammatory arteritis, and congenital heart disease and acquired valvular heart disease. Pulmonary arterial hypertension can cause ...

  5. Current and advancing treatments for pulmonary arterial hypertension in childhood

    NARCIS (Netherlands)

    Zijlstra, Willemijn M. H.; Ploegstra, Mark-Jan; Berger, Rolf M. F.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a severe and progressive intrinsic disease of the precapillary lung vasculature. Since the introduction of PAH-targeted drugs, survival of PAH patients seems to have improved. Randomized controlled trials have led to evidence-based guidelines to direct

  6. A Special Focus on Selexipag - Treatment of Pulmonary Arterial Hypertension

    DEFF Research Database (Denmark)

    Sørensen, Louise Marqvard; Wehland, Markus; Krüger, Marcus

    2017-01-01

    BACKGROUND: This review focuses on the treatment of pulmonary arterial hypertension (PAH) with selexipag and compares its drug-related therapeutic effects with those of prostacyclin analogues. METHODS: We searched the relevant literature and summarized the current clinical trials concerning selex...

  7. Genetic Associations With Hypoxemia and Pulmonary Arterial Pressure in COPD*

    Science.gov (United States)

    Castaldi, Peter J.; Hersh, Craig P.; Reilly, John J.; Silverman, Edwin K.

    2010-01-01

    Background Hypoxemia, hypercarbia, and pulmonary arterial hypertension are known complications of advanced COPD. We sought to identify genetic polymorphisms associated with these traits in a population of patients with severe COPD from the National Emphysema Treatment Trial (NETT). Methods In 389 participants from the NETT Genetics Ancillary Study, single-nucleotide polymorphisms (SNPs) were genotyped in five candidate genes previously associated with COPD susceptibility (EPHX1, SERPINE2, SFTPB, TGFB1, and GSTP1). Linear regression models were used to test for associations among these SNPs and three quantitative COPD-related traits (Pao2, Paco2, and pulmonary artery systolic pressure). Genes associated with hypoxemia were tested for replication in probands from the Boston Early-Onset COPD Study. Results In the NETT Genetics Ancillary Study population, SNPs in microsomal epoxide hydrolase (EPHX1) [p = 0.01 to 0.04] and serpin peptidase inhibitor, clade E, member 2 (SERPINE2) [p = 0.04 to 0.008] were associated with hypoxemia. One SNP within surfactant protein B (SFTPB) was associated with pulmonary artery systolic pressure (p = 0.01). In probands from the Boston Early-Onset COPD Study, SNPs in EPHX1 and in SERPINE2 were associated with the requirement for supplemental oxygen. Conclusions In participants with severe COPD, SNPs in EPHX1 and SERPINE2 were associated with hypoxemia in two separate study populations, and SNPs from SFTPB were associated with pulmonary artery pressure in the NETT participants. PMID:19017876

  8. [Arterial stiffness in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    2012-01-01

    To estimate arterial stiffness (AS) in patients with chronic obstructive pulmonary disease (COPD). A total of 112 COPD patients over 40 years of age entered a population-based trial. The patients with coronary heart diseases, peripheral vascular atherosclerosis, other severe chronic diseases in exacerbation were withdrawn. The control group consisted of 26 healthy volunteers matched by gender and age. AS was measured at arteriograph "Tensioclinic" ("Tensiomed", Hungary). COPD patients, first of all elderly ones, had abnormal properties of arterial wall. Increased arterial rigidity and pulse wave reflection (accelerated pulse wave velocity and high index of augmentation) are strongly associated with elevation of central arterial pressure. High arterial wall stiffness in COPD patients suggests an increased risk of cardiovascular diseases that necessitates examination in prospective studies.

  9. Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT

    Energy Technology Data Exchange (ETDEWEB)

    Hoey, Edward T.D.; Gopalan, Deepa; Agrawal, S.K.B. [Papworth Hospital, Cambridge (United Kingdom); Screaton, Nicholas J. [Papworth Hospital, Cambridge (United Kingdom); Papworth Hospital NHS Trust, Diagnostic Centre, Department of Radiology, Papworth Everard, Cambridgeshire (United Kingdom)

    2009-11-15

    The causes of pulmonary arterial hypertension (PAH) are diverse and include multiple congenital and acquired cardiac diseases as well as diseases primarily affecting the pulmonary vasculature, lung, pleura and chest wall. The traditional role of CT in evaluating PAH includes assessment of pulmonary vasculature and lung parenchyma with limited assessment of the heart. Advances in multidetector CT technology with improved spatial and temporal resolution now permit accurate delineation of cardiac morphology. CT pulmonary angiography (CTPA) is widely utilised in the workup of patients with suspected pulmonary vascular disease and can identify both pulmonary and cardiac causes. As the initial presentation for CTPA is often precipitated by nonspecific, unexplained symptoms and therefore undertaken by a general radiologist, it is important that a systematic approach to the interpretation of these studies, including cardiac evaluation, is routinely adopted. This paper reviews the CT evaluation in pulmonary hypertension with a particular focus on the cardiac causes, their subclassification into congenital systemic to pulmonary shunts and secondary to left heart disease, and their imaging features. It emphasises the use of a systematic approach to interpretation of CTPA examinations both in patients with known PAH and those with previously unsuspected disease. (orig.)

  10. [Stent implantation for relief of pulmonary artery branch stenosis].

    Science.gov (United States)

    Guo, Ying; Yu, Zhiqing; Liu, Tingliang; Gao, Wei; Huang, Meirong; Li, Fen; Fu, Lijun; Zhao, Pengjun

    2014-05-01

    Branch pulmonary artery stenosis is one of the common congenital heart disease. Stent implantation to relieve branch pulmonary artery stenosis (BPAS) is an alternative to failed surgical or balloon angioplasty. The aim of this study was to explore the indication, methods and complications of using balloon expandable stent placement to treat branch pulmonary artery stenosis, and evaluate the results of stent implantation in the treatment of branch pulmonary artery stenosis. From August 2005 to December 2012, 19 patients underwent an attempt at stent implantation. The median age of those patients was 9.1 years (range 4.0-15.0 years). The median weight was 31.7 kg (range 17.0-60.5 kg); 14/19 patients underwent post surgical repair of tetralogy of Fallot, one patient received post surgical repair of pulmonary atresia with ventricular septal defect, one patient underwent post surgical repair of pulmonary atresia with intact septum, one with native left BPAS, and one was after surgical repair of aortopulmonary window and the other truncus arteriosus. CP stent and NuMED Balloon-in-Balloon catheter were selected according to digital subtracted angiography measurements. After checking for correct position by angiography, the inner balloon and outer balloon was inflated successively to expand the stent to desired diameter. Statistical analysis was performed with the unpaired Student t test. A total of 26 stents were implanted successfully in 19 patients. The systolic gradient across the stenosis fell from a median of (36.0 ± 18.3) to (3.8 ± 3.4) mmHg (P aortic pressure ratio fell from 0.68 to 0.49 (P children will require further dilation to keep up with normal somatic growth. Intermediate and long-term follow up studies have shown excellent results after further dilation over time.

  11. Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension.

    Science.gov (United States)

    Hao, Mingwen; Li, Miaomiao; Li, Wenjun

    2017-01-01

    Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal‑3‑/‑ mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal‑3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal‑3 in wild type murine pulmonary arteries. Gal‑3 deletion reduced the hypoxia‑induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal‑3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal‑3 inhibition alleviated the hypoxia‑induced inflammatory response in HPAECs, including tumor necrosis factor‑α and interleukin‑1 secretion, expression of intercellular adhesion molecule‑1 and adhesion of THP‑1 monocytes. Gal‑3 inhibition also reduced hypoxia‑induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal‑3 inhibition suppressed HPASMC switching from a 'contractile' to a 'synthetic' phenotype. In conclusion, Gal‑3 serves a fundamental role in hypoxia‑induced PAH, and inhibition of Gal‑3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH.

  12. Anomalous origin of the left coronary artery from the pulmonary artery in children: diagnostic use of multidetector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Quanli; Yao, Qiong; Hu, Xihong [Children' s Hospital of Fudan University, Department of Radiology, Shanghai (China)

    2016-09-15

    Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly. It is important to demonstrate the anomalous origin of the left coronary artery and its course before surgery. To explore the clinical diagnostic use of multidetector CT coronary angiography in detecting anomalous origin of the left coronary artery from the pulmonary artery in children. Nine children (2 boys, 7 girls) ages 2 months to 9 years with surgically confirmed anomalous origin of the left coronary artery from the pulmonary artery were studied. Clinical data, transthoracic echocardiography and CT coronary angiography images were retrospectively analyzed. Transthoracic echocardiography correctly diagnosed anomalous origin of the left coronary artery from the pulmonary artery in 7 of 9 patients (95% CI: 40-97%). CT coronary angiography revealed the anomalous origin of the left coronary artery in all children (95% CI: 66-100%). In a 4-year-old girl and a 9-year-old girl, CT coronary angiography showed dilation of the right coronary artery and collateral circulation between the right and the left coronary arteries. CT coronary angiography is a useful method to show the anomalous origin of the coronary artery in children with anomalous origin of the left coronary artery from the pulmonary artery, especially for patients in whom origin of the left coronary artery cannot be detected by transthoracic echocardiography. (orig.)

  13. Left pulmonary artery banding to repair ipsilateral diffuse pulmonary arteriovenous fistula

    Directory of Open Access Journals (Sweden)

    Hirata Takuya

    2012-08-01

    Full Text Available Abstract Congenital pulmonary arteriovenous fistula (PAVF is a rare disease which causes hypoxemia by shunting deoxygenated blood from the pulmonary artery into pulmonary venous return. Lung transplantation is the most effective therapy to treat severe, diffuse PAVF. However, the availability of lungs for transplantation is limited in most parts in the world. For patients with diffuse PAVF affecting only one side of the lungs, ipsilateral pulmonary artery banding (PAB is an effective treatment, but not yet standard of care. We report successful treatment of a patient with diffuse left-sided PAVF with PAB. We believe that PAB is an effective therapy for severe unilateral PAVF and may serve as a bridge to lung transplantation.

  14. Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease

    OpenAIRE

    Coste, Florence; Guibert, Christelle; Magat, Julie; Abell, Emma; Vaillant, Fanny; Dubois, Mathilde; Courtois, Arnaud; Diolez, Philippe; Quesson, Bruno; Marthan, Roger; Savineau, Jean-Pierre; Muller, Bernard; Freund-Michel, V?ronique

    2017-01-01

    Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension that combines multiple alterations of pulmonary arteries, including, in particular, thrombotic and plexiform lesions. Multiple-pathological-insult animal models, developed to more closely mimic this human severe PAH form, often require complex and/or long experimental procedures while not displaying the entire panel of characteristic lesions observed in the human disease. In this study, we further characterized a...

  15. Congenital anomalies of the pulmonary arteries: spectrum of findings on computed tomography.

    Science.gov (United States)

    Bueno, J; Flors, L; Mejía, M

    Congenital anomalies of the pulmonary arteries are uncommon. They can occur in isolation or in association with congenital heart defects. Isolated congenital anomalies remain undiscovered until they are reported as incidental findings on imaging tests, usually not until adolescence. We review the embryological development and normal anatomy of the pulmonary arteries as well as the spectrum of computed tomography findings for various congenital anomalies: unilateral interruption of the pulmonary artery, anomalous origin of the left pulmonary artery (pulmonary artery sling), idiopathic aneurysm of the pulmonary artery, and other anomalies associated with congenital heart defects. Congenital anomalies of the pulmonary arteries represent a diagnostic challenge for clinicians and radiologists. Computed tomography is useful for their diagnosis, and general radiologists need to be familiar with their imaging appearance because they are often discovered incidentally. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Asymptomatic Right Coronary Artery-to-Pulmonary Artery Fistula Incidentally Detected by Transthoracic Echocardiography.

    Science.gov (United States)

    Lim, Woo-Hyun; Kang, Si-Hyuck; Jeon, Kihyun; Cho, Iksung; Kim, Kyung-Hee; Hwang, Sung-Wook; Kim, Hyung-Kwan; Sohn, Dae-Won

    2009-09-01

    In this case report, we describe a 71-year-old woman with right conal coronary artery-to-pulmonary trunk fistula. She visited the outpatient clinic of the nephrology department for long-term management of renal dysfunction. On transthoracic echocardiography (TTE) conducted as a part of cardiac evaluation, an abnormal Doppler color flow taking a course toward echocardiographic probe was incidentally detected outside the main pulmonary trunk, giving an impression of congenital coronary arteriovenous (AV) fistula. Computed tomography coronary angiography confirmed the presence of congenital coronary AV fistula from a conal branch of the right coronary artery to the main pulmonary trunk in the form of a ground cherry. Although the direction of Doppler color flow is not usual (i.e. toward, not away from, echocardiographic probe) in this case, congenital coronary AV fistula should be in the first priority among potential diagnoses when an abnormal Doppler color flow was found near the main pulmonary trunk on TTE.

  17. [Rehabilitation of hypoplastic pulmonary arteries and anatomic correction of pulmonary atresia with interventricular communication].

    Science.gov (United States)

    Chetaille, P; Fraisse, A; Ghez, O; Kreitmann, B; Voisin, M; Aubert, F; Metras, D

    2001-05-01

    Conventional treatment of pulmonary atresia with ventricular septal defect (VSD), hypoplastic pulmonary arteries (PA) and major aorto-pulmonary collaterals (MAPCAs) is controversial: from symptomatic and palliative treatment for some authors to surgery with unifocalisation of collaterals for others. These treatments never use native pulmonary arteries as only source of pulmonary flow, but create "neo-pulmonary arteries". Nine cases of pulmonary atresia with VSD, hypoplastic PA and MAPCAs were treated by rehabilitation of native PA through a staged approach: 1) surgical neonatal connection between right ventricule (RV) and hypoplastic PA, 2) evaluation and interventionnal catheterism with angioplasty of PA stenosis and closure of collaterals, 3) complete surgical correction with reconstruction of right outflow track and PA and closure of VSD. After first surgical stage of RV-PA connection at the mean age of 4.8 months (+/- 5.6 months), 8 patients were alive and underwent 22 cardiac catheterisms (mean of 2.7 per patient), with angioplasty of PA, and occlusion of MAPCAs in 6 and 2 patients respectively. Seven patients underwent complete anatomical correction at the mean age of 28.8 months (+/- 17.7 months) with one late death. The 6 remaining patients had encouraging hemodynamic status (RV pressure/LV pressure ratio at 0.6 +/- 0.26; mean left and right distal pulmonary pressure at 15.2 mmHg (+/- 9.1 mmHg)), and good functionnal status (3 in NYHA functionnal class 1, and 3 in class 2), for a mean follow-up of 79.5 months (+/- 41.4 months). One patient had reoperation on right outflow track stenosis, 6 years after correction. This small series enhances the feasibility of a staged approach with rehabilitation of small PA, allowing complete surgical correction with the native PA with good hemodynamic and functional results in pulmonary atresia, with VSD, hypoplastic PA and MAPCAs.

  18. Medical image of the week: pulmonary artery sling

    Directory of Open Access Journals (Sweden)

    Agrawal A

    2017-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 42-year-old year woman with asthma was admitted to the hospital with an asthma exacerbation. The patient complained of dyspnea on exertion, two-pillow orthopnea and bipedal edema. An echocardiogram showed a severely dilated right ventricle (RV with elevated right ventricular systolic pressure of 71 mmHg. The systolic left ventricular (LV function was also reduced with an ejection fraction of 45%. Computerized tomography (CT of the chest showed an aberrant origin of the left pulmonary artery (PA creating a pulmonary artery sling with mild tracheal narrowing (Figure 1, arrow. Cardiac magnetic resonance imaging (MRI confirmed the presence of a pulmonary artery sling with the aberrant origin of the left PA from the right PA (Figure 2. Cardiac catheterization showed a mean PA pressure of 46mmHg with LV end diastolic pressure of 12mm Hg. The patient was diagnosed with WHO Group I pulmonary hypertension and started on treatment with sildenafil with a …

  19. Adenosine Receptors As Drug Targets for Treatment of Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Allan K. N. Alencar

    2017-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a clinical condition characterized by pulmonary arterial remodeling and vasoconstriction, which promote chronic vessel obstruction and elevation of pulmonary vascular resistance. Long-term right ventricular (RV overload leads to RV dysfunction and failure, which are the main determinants of life expectancy in PAH subjects. Therapeutic options for PAH remain limited, despite the introduction of prostacyclin analogs, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and soluble guanylyl cyclase stimulators within the last 15 years. Through addressing the pulmonary endothelial and smooth muscle cell dysfunctions associated with PAH, these interventions delay disease progression but do not offer a cure. Emerging approaches to improve treatment efficacy have focused on beneficial actions to both the pulmonary vasculature and myocardium, and several new targets have been investigated and validated in experimental PAH models. Herein, we review the effects of adenosine and adenosine receptors (A1, A2A, A2B, and A3 on the cardiovascular system, focusing on the A2A receptor as a pharmacological target. This receptor induces pulmonary vascular and heart protection in experimental models, specifically models of PAH. Targeting the A2A receptor could potentially serve as a novel and efficient approach for treating PAH and concomitant RV failure. A2A receptor activation induces pulmonary endothelial nitric oxide synthesis, smooth muscle cell hyperpolarization, and vasodilation, with important antiproliferative activities through the inhibition of collagen deposition and vessel wall remodeling in the pulmonary arterioles. The pleiotropic potential of A2A receptor activation is highlighted by its additional expression in the heart tissue, where it participates in the regulation of intracellular calcium handling and maintenance of heart chamber structure and function. In this way, the activation of A2A

  20. Peptide-Directed Highly Selective Targeting of Pulmonary Arterial Hypertension

    Science.gov (United States)

    Urakami, Takeo; Järvinen, Tero A.H.; Toba, Michie; Sawada, Junko; Ambalavanan, Namasivayam; Mann, David; McMurtry, Ivan; Oka, Masahiko; Ruoslahti, Erkki; Komatsu, Masanobu

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary vasculature associated with elevated pulmonary vascular resistance. Despite recent advances in the treatment of PAH, with eight approved clinical therapies and additional therapies undergoing clinical trials, PAH remains a serious life-threatening condition. The lack of pulmonary vascular selectivity and associated systemic adverse effects of these therapies remain the main obstacles to successful treatment. Peptide-mediated drug delivery that specifically targets the vasculature of PAH lungs may offer a solution to the lack of drug selectivity. Herein, we show highly selective targeting of rat PAH lesions by a novel cyclic peptide, CARSKNKDC (CAR). Intravenous administration of CAR peptide resulted in intense accumulation of the peptide in monocrotaline-induced and SU5416/hypoxia-induced hypertensive lungs but not in healthy lungs or other organs of PAH rats. CAR homed to all layers of remodeled pulmonary arteries, ie, endothelium, neointima, medial smooth muscle, and adventitia, in the hypertensive lungs. CAR also homed to capillary vessels and accumulated in the interstitial space of the PAH lungs, manifesting its extravasation activity. These results demonstrated the remarkable ability of CAR to selectively target PAH lung vasculature and effectively penetrate and spread throughout the diseased lung tissue. These results suggest the clinical utility of CAR in the targeted delivery of therapeutic compounds and imaging probes to PAH lungs. PMID:21549345

  1. 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.

  2. Pulmonary arterial hypertension in a patient with stage II sarcoidosis and Hashitoxicosis

    Directory of Open Access Journals (Sweden)

    S. Ocak

    2009-06-01

    Full Text Available Although pulmonary arterial hypertension is usually associated with advanced stages of sarcoidosis, its occurrence in early stage disease is rare. Herein, a case of associated pulmonary arterial hypertension in the setting of Hashitoxicosis and stage II pulmonary sarcoidosis is reported. The case of associated pulmonary arterial hypertension occurred in a young female without clinically significant medical history and who completely recovered after receiving oral corticotherapy only. Furthermore, this case report suggests the presence of an interaction between pulmonary arterial hypertension, sarcoidosis and Hashitoxicosis.

  3. Surgical repair for a coronary-pulmonary artery fistula with a saccular aneurysm of the coronary artery.

    Science.gov (United States)

    Izumi, Kenta; Hisata, Yoichi; Hazam, Shiro

    2009-06-01

    The patient, a 69-year-old woman, had been diagnosed with a heart murmur. A chest X-ray at a local clinic had shown an abnormal shadow. Since CT revealed a 3-cm-diameter mass close to the pulmonary artery, we performed a coronary angiography and diagnosed her as having a coronary artery aneurysm associated with a coronary-pulmonary artery fistula. We incised the aneurysm under cardiac arrest, the wall of which had three openings that were suture closed from the inside and outside. The coronary-pulmonary artery fistula was suture closed. A postoperative angiography confirmed the disappearance of the coronary artery aneurysm and the abnormal blood vessels. The patient had an uneventful postoperative course and was discharged on postoperative day 15. We report a rare case of coronary-pulmonary artery fistula with a coronary artery aneurysm for which surgery was followed by an uneventful postoperative course.

  4. Patient engagement and self-management in pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Graarup, Jytte; Ferrari, Pisana; Howard, Luke S

    2016-01-01

    of pulmonary arterial hypertension management, which places the patient at the centre of their own healthcare. Patients are thus becoming more proactive, involved and engaged in their self-care, and this engagement is an important factor if patient outcomes are to improve. In addition, involvement...... of the patient may improve their ability to cope with pulmonary arterial hypertension, as well as help them to become effective in the self-management of their disease. Successful patient engagement can be achieved through effective education and the delivery and communication of timely, high-quality information....... A multidisciplinary approach involving healthcare professionals, carers, patient associations and expert patient programmes can also encourage patients to engage. Strategies that promote patient engagement can help to achieve the best possible care and support for the patient and also benefit healthcare providers....

  5. Clopidogrel in infants with systemic-to-pulmonary-artery shunts

    DEFF Research Database (Denmark)

    Wessel, David L; Berger, Felix; Li, Jennifer S

    2013-01-01

    BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related...... to the shunt. METHODS: In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants...... days of age. RESULTS: The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P...

  6. Role of Dimethylarginine Dimethylaminohydrolases (DDAH) in pulmonary arterial hypertension

    OpenAIRE

    Pullamsetti, Soni

    2005-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and life- limiting disorder which is associated with impaired bioactivity and/or synthesis of endogenous nitric oxide (NO). The mechanisms resulting in this impairment are multifactorial. Recently, the impact of endogenous NO-synthase inhibitors such as dimethylarginines (ADMA and SDMA) has come into the focus of attention for various endothelial dysfunction associated cardiovascular disorders. As current evidence strongly sug...

  7. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

    OpenAIRE

    Serra Walter; Chetta Alfredo; Santilli Daniele; Mozzani Flavio; Dall'Aglio Pier; Olivieri Dario; Cattabiani Maria; Ardissino Diego; Gherli Tiziano

    2010-01-01

    Abstract Background Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. Objectives The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic scleros...

  8. Pulmonary artery endothelial cell phenotypic alterations in a large animal model of pulmonary arteriovenous malformations after the Glenn shunt.

    Science.gov (United States)

    Kavarana, Minoo N; Mukherjee, Rupak; Eckhouse, Shaina R; Rawls, William F; Logdon, Christina; Stroud, Robert E; Patel, Risha K; Nadeau, Elizabeth K; Spinale, Francis G; Graham, Eric M; Forbus, Geoffrey A; Bradley, Scott M; Ikonomidis, John S; Jones, Jeffrey A

    2013-10-01

    Longevity of the superior cavopulmonary connection (SCPC) is limited by the development of pulmonary arteriovenous malformations (PAVM). The goal of this study was to determine whether phenotypic changes in pulmonary artery endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation. A superior vena cava to right pulmonary artery connection was constructed in 5 pigs. Pulmonary arteries were harvested at 6 to 8 weeks after surgery to establish cultures of PAEC and smooth muscle cells, to determine cell proliferation, gene expression, and tubule formation. Abundance of proteins related to angiogenesis was measured in lung tissue. Contrast echocardiography revealed right-to-left shunting, consistent with PAVM formation. While the proliferation of smooth muscle cells from the right pulmonary artery (shunted side) and left pulmonary artery (nonshunted side) were similar, right PAEC proliferation was significantly higher. Expression profiles of genes encoding cellular signaling proteins were higher in PAECs from the right pulmonary artery versus left pulmonary artery. Protein abundance of angiopoietin-1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both p SCPC concomitantly with differential changes in PAEC proliferative ability and phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2 complex in the right lung, which may provide novel therapeutic targets to attenuate PAVM formation after a SCPC. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Left Pulmonary Artery Agenesis in a Pediatric Patient – Case Report

    Directory of Open Access Journals (Sweden)

    Blesneac Cristina

    2016-06-01

    Full Text Available Unilateral pulmonary artery agenesis is a rare congenital anomaly, that may develop in isolation, or in association with other congenital cardiovascular anomalies, such as tetralogy of Fallot, septal defects, right-sided aortic arch, or pulmonary atresia. Left-sided pulmonary artery agenesis is less frequent than the right-sided one. Diagnosis of unilateral pulmonary artery agenesis can be difficult. We report the case of a 15 year-old boy who presented with reduced exercise tolerance, shortness of breath and cyanosis. He was diagnosed with left pulmonary artery agenesis, associated with subaortic-ventricular septal defect, right-sided aortic arch, and severe pulmonary arterial hypertension (PAH, that precluded the surgical repair. Pulmonary vasodilator therapy was initiated in this case. The mortality rate of this rare anomaly is high due to its complications. It is essential to establish an early and correct diagnosis, in order to provide adequate treatment and prevent complications in this disease.

  10. [Cardiac catheterization and pulmonary vasoreactivity testing in children with idiopathic pulmonary arterial hypertension].

    Science.gov (United States)

    Zhang, Chen; Li, Qiangqiang; Liu, Tianyang; Gu, Hong

    2014-06-01

    As an important method of hemodynamic assessment in idiopathic pulmonary arterial hypertension (IPAH), cardiac catheterization combined with pulmonary vasoreactivity testing remains with limited experience in children, and the acute pulmonary vasodilator agents as well as response criteria for vasoreactivity testing remain controversial. The aim of this study was to investigate the clinical importance, agent selection, and responder definition of cardiac catheterization combined with pulmonary vasoreactivity testing in pediatric IPAH. The patients admitted to Department of Pediatric Cardiology of Beijing Anzhen Hospital between April 2009 and September 2013 with suspected IPAH, under 18 years of age, with WHO functional class II or III, were enrolled. All the patients were arranged to receive left and right heart catheterization and pulmonary vasoreactivity testing with inhalation of pure oxygen and iloprost (PGI2) respectively. Hemodynamic changes were analyzed, and two criteria, the European Society of Cardiology recommendation criteria (Sitbon criteria) and traditional application criteria (Barst criteria), were used to evaluate the test results. Thirty-nine cases of children with suspected IPAH underwent cardiac catheterization. In 4 patients IPAH was excluded; 4 patients developed pulmonary hypertension crisis. The other 31 patients received standard cardiac catheterization and pulmonary vasoreactivity testing. Baseline mean pulmonary artery pressure (mPAP) was (66 ± 16) mmHg (1 mmHg = 0.133 kPa), and pulmonary vascular resistance index (PVRI) (17 ± 8) Wood U · m². After inhalation of pure oxygen, mPAP fell to (59 ± 16) mmHg, and PVRI to (14 ± 8) Wood U · m² (t = 4.88 and 4.56, both P children with IPAH, cardiac catheterization combined with pulmonary vasoreactivity testing has important value in differential diagnosis, severity estimation, and treatment (including the emergency treatment) choices. Pulmonary hypertension crisis is an important

  11. Nonthrombotic Pulmonary Artery Embolism: Imaging Findings and Review of the Literature.

    Science.gov (United States)

    Unal, Emre; Balci, Sinan; Atceken, Zeynep; Akpinar, Erhan; Ariyurek, Orhan Macit

    2017-03-01

    The purpose of this article is to emphasize the imaging findings encountered in the setting of nonthrombotic pulmonary embolism. Nonthrombotic pulmonary embolism refers to a spectrum of clinical and radiologic disorders caused by embolization of the pulmonary artery vasculature by various cell types, microorganism, and foreign bodies. Awareness of the imaging and clinical features of the nonthrombotic pulmonary embolism may facilitate prompt diagnosis.

  12. Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes

    Directory of Open Access Journals (Sweden)

    Elshaboury SM

    2013-05-01

    Full Text Available Soha M Elshaboury,1 Joe R Anderson21College of Pharmacy, University of New Mexico, 2Pharmacy Practice and Internal Medicine, College of Pharmacy and School of Medicine, University of New Mexico, Albuquerque, NM, USAAbstract: Pulmonary arterial hypertension (PAH is a progressive disease of the pulmonary vasculature that is associated with severe functional impairment and a poor prognosis. Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1. The efficacy and safety of ambrisentan has been evaluated in the ARIES series (Ambrisentan for the Treatment of Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies, which has established its use as both monotherapy or in conjunction with other PAH therapies. Specifically, ambrisentan is effective at increasing exercise tolerance, decreasing the risk of functional class deterioration, and prolonging time to clinical worsening. Further, ambrisentan has a favorable effect on mortality, with an 88% patient survival rate after two years of therapy compared with a 61% survival rate as estimated by the National Institute of Health Registry. Ambrisentan is generally well tolerated in all patient groups, with the main side effects of peripheral edema, sinusitis, flushing, and nasal congestion considered to be mild to moderate in nature. Ambrisentan has several favorable qualities that potentially make it more acceptable to patients, including once-daily administration, limited adverse drug reactions and drug-drug interactions, and minimal risk of liver enzyme elevation. Because of the potential risk of teratogenicity associated with ambrisentan, it is only available through a limited distribution program, ie, LEAP (the Letairis Education and Access Program. Ongoing clinical trials will help to clarify the role of ambrisentan in the treatment of PAH.Keywords: ambrisentan

  13. Visualization of peripheral pulmonary artery red thrombi utilizing optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Cheng; Wang, Wei; Zhong, Nan Shan; Zeng, Guang Qiao; Zhang, Nuo Fu [The First Affiliated Hospital of Guangzhou Medical College, Guangzhou (China)

    2013-10-15

    Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.

  14. Pulmonary artery rupture in a patient receiving an orthotopic heart transplant after total artificial heart explant.

    Science.gov (United States)

    Nomoto, Koichi; Weiner, Menachem M; Evans, Adam

    2014-02-01

    Our case illustrates a patient who suffered a pulmonary artery rupture despite previous total artificial heart implantation and replacement with orthotopic heart transplant. Pulmonary artery rupture during or following cardiac surgery has been reported to occur due to both pulmonary artery catheter use and surgical technique. Our case is the first to demonstrate the occurrence of this complication in the total artificial heart patient population.

  15. The anomalous origin of the branch pulmonary artery from the ascending aorta

    OpenAIRE

    Garg, Pankaj; Talwar, Sachin; Kothari, Shyam Sunder; Saxena, Anita; Juneja, Rajnish; Choudhary, Shiv Kumar; Airan, Balram

    2012-01-01

    The anomalous origin of one pulmonary artery branch from the aorta (AOPA) is rare. We report our single-institution surgical experience with this condition. Between January 1994 and February 2011, 17 patients (age: 1 month–25 years) with AOPA underwent surgery at our institute. Thirteen patients had an anomalous origin of the right pulmonary artery (RPA) while four had an anomalous origin of the left pulmonary artery (LPA) from the aorta. In patients with anomalous RPA, 11 patients had the pr...

  16. Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Borst Mathias M

    2009-12-01

    Full Text Available Abstract Background In idiopathic pulmonary arterial hypertension (IPAH, peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1, to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction. Methods In 32 IPAH-patients (19 female, WHO functional class II (n = 10, III (n = 22; (data presented as mean ± standard deviation pulmonary vascular resistance (11 ± 5 Wood units, lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0 m, systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg, and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0 ng/L were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day. Results and Discussion At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p Conclusion This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.

  17. [Analysis of factors related to pulmonary hypertensive crisis in patients with idiopathic pulmonary arterial hypertension].

    Science.gov (United States)

    Zhang, Chen; Li, Qiangqiang; Zhu, Yan; Gu, Hong

    2014-06-10

    To explore the risk and protective factors for pulmonary hypertensive crisis (PHC) in patients with idiopathic pulmonary arterial hypertension (IPAH). A retrospective study was performed for 65 patients with a diagnosis of IPAH between January 2010 and December 2013. According to clinical manifestations, they were divided into two groups of susceptibility and non-susceptibility to PHC. Clinical and hemodynamic parameters were analyzed in univariate and multivariate manners. Among them, there were 32 males and 33 females with a mean age of (14.4 ± 12.3) (10/12-47.3) years. Twenty-three patients had typical manifestations of PHC and 18 of them were induced by exercises.Univariate analysis revealed that the proportion of patients with World Health Organization (WHO) functional class III-IV in PHC-susceptible group was significantly higher than PHC-nonsusceptible group (60.9% vs 23.8%, P = 0.003) while the percentage of patent foramen ovale in PHC-susceptible group was significantly lower than PHC-nonsusceptible group (8.7% vs 45.2%, P = 0.003).In patients with WHO functional classI-II, hemodynamic variables including the decline of pulmonary arterial pressure and positive rate in vasoreactivity testing in PHC-susceptible group were significantly higher than PHC-nonsusceptible group.In patients with WHO functional class III-IV, baseline pulmonary arterial pressure and mean right atrial pressure in PHC-susceptible group were significantly higher than those in PHC-nonsusceptible group. Multivariate Logistic regression analysis revealed that, for those with WHO functional class III-IV (OR = 23.45, 95%CI: 2.85-193.09) and the decline of systolic pulmonary arterial pressure in vasoreactivity testing (OR = 1.12, 95%CI: 1.04-1.22) were independent risk factors for PHC in IPAH patients while patent foramen ovale (OR = 0.01, 95%CI: 0.00-0.52) was a protective factor. PHC in IPAH patients is correlated with WHO functional class, pulmonary vascular reactivity, baseline pulmonary

  18. Secretory clusterin is upregulated in rats with pulmonary arterial hypertension induced by systemic-to-pulmonary shunts and exerts important roles in pulmonary artery smooth muscle cells.

    Science.gov (United States)

    Liu, X; Meng, L; Li, J; Meng, J; Teng, X; Gu, H; Hu, S; Wei, Y

    2015-02-01

    Phenotype modification of pulmonary artery smooth muscle cells (PASMCs) (excessive proliferation, migration and impaired apoptosis) plays central roles in pulmonary vascular remodelling of pulmonary arterial hypertension (PAH); however, the potential mechanism and contributing factors involved in the phenotype alteration in PASMCs are still not completely elucidated. This study attempted to investigate the expression pattern of secretory clusterin (sCLU), a prosurvival protein, in systemic-to-pulmonary shunt-induced PAH rats and the potential roles of sCLU in pulmonary vascular remodelling. An original rat model of systemic-to-pulmonary shunt-induced PAH was established by combined surgery as we previously reported. Lung tissues were harvested at specific time points for real-time polymerase chain reaction, Western blot and immunohistochemisty analysis; meanwhile, plasma was collected for enzyme-linked immunosorbent assay. Cell culture experiments were performed using cultured human PASMCs (HPASMCs). Expression of sCLU was significantly increased in lungs exposed to systemic-to-pulmonary shunt. Moreover, plasma sCLU levels were markedly elevated with the progression of PAH in rats and also presented a positive correlation with pulmonary hemodynamic indices. In vitro cell culture assay indicated that sCLU expression and secretion increased with the phenotype modification of HPASMCs; furthermore, sCLU promoted HPASMCs proliferation, migration and apoptosis resistance, at least in part, via Erk1/2 and Akt signalling pathways. These results demonstrate that sCLU is functionally an important phenotype modulator of PASMCs, and its upregulation in lung tissues may exert a deteriorative role in pulmonary vascular remodelling. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  19. Coronary artery to pulmonary artery communications in pulmonary atresia with ventricular septal defect

    National Research Council Canada - National Science Library

    Sridhar, Anuradha; Subramanyan, Raghavan; Cherian, Kotturathu Mammen

    2013-01-01

    ...% of patients with pulmonary atresia and ventricular septal defect (PA-VSD). A diligent look for these abnormal communications is important to prevent perioperative complications and achieve a complete repair...

  20. Novel formula to measure mean pulmonary artery pressure

    Directory of Open Access Journals (Sweden)

    Francisco Jose Chacon-Lozsan

    2016-11-01

    Full Text Available Mean Pulmonary Arterial Pressure (MPAP is an important parameter in evaluation of patients with pulmonary hypertension. The aim of this study is to correlate a new formula using non-invasive blood pressure and Bernoulli’s right ventricle systolic pressure (RVSP with invasive method. To archive the objectives, we enrolled 143 patients with suspected pulmonary hypertension from January 2015 till January 2016; all patients underwent right heart catheter evaluation and simultaneously RVSP by transthoracic echocardiography and non-invasive blood pressure to calculate MPAP by the formula MPAP = Pulse Pressure / (Mean Arterial Pressure/RVSP; and the results were compared using the Pearson’s simple-linear correlation method. We found a significant association between invasive and equation results with a Pearson’s correlation of 0,872 with a confidence interval from 0,795 to 0,921; sensitivity was 1,538% with a 95% confidence of interval (CI from 0,038% to 8,276%, and Specificity was 100% with 95% CI from 94,48% to 100%. Our results suggest that the new formula have a good correlation estimating MPAP compared with invasive right heart catheterization method.

  1. Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan, Jason X; Vanderpool, Rebecca; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

    2018-02-05

    Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricle dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well-characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, gender, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P=0.012), along with reduced log(pulmonary artery capacitance) (P=0.006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018. Published by Elsevier Inc.

  2. Echocardiographic presentation of anomalous origin of the left coronary artery from the pulmonary artery.

    Science.gov (United States)

    Silverman, Norman H

    2015-12-01

    In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients.

  3. Left Ventricular Thrombus Formation After Repair of Anomalous Left Coronary Artery From the Pulmonary Artery

    Science.gov (United States)

    Freud, Lindsay R.; Koenig, Peter R.; Russell, Hyde M.; Patel, Angira

    2014-01-01

    Although thrombus formation following myocardial infarction in adults is well known, intracardiac thrombosis in children is uncommon. We report the case of a large left ventricular thrombus in an infant with ischemic cardiomyopathy secondary to anomalous origin of the left coronary artery from the pulmonary artery. Given its mobility and protrusion across the aortic valve, the patient underwent urgent thrombus removal through a transaortic approach. There were no embolic or neurologic complications. This case highlights that thrombectomy may be performed safely and successfully in critically ill pediatric patients. PMID:24668990

  4. Anesthesia for cesarean section in a patient with isolated unilateral absence of a pulmonary artery.

    Science.gov (United States)

    Furuya, Tomonori; Iida, Ryoji; Konishi, Jyumpei; Kato, Jitsu; Suzuki, Takahiro

    Congenital unilateral absence of a pulmonary artery (UAPA) is a rare anomaly. Although there are several reports regarding pregnancy in patients with unilateral absence of a pulmonary artery, there are no case reports describing anesthesia for Cesarean section in a patient with unilateral absence of a pulmonary artery. We present a patient with unilateral absence of a pulmonary artery who underwent Cesarean sections twice at the ages of 24 and 26 years under spinal anesthesia for surgery and epidural analgesia for postoperative pain relief. Both times, spinal anesthesia and epidural analgesia enabled successful anesthesia management without the development of either pulmonary hypertension or right heart failure. Spinal anesthesia combined with epidural analgesia is a useful anesthetic method for a Cesarean section in patients with unilateral absence of a pulmonary artery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  5. [Anesthesia for cesarean section in a patient with isolated unilateral absence of a pulmonary artery].

    Science.gov (United States)

    Furuya, Tomonori; Iida, Ryoji; Konishi, Jyumpei; Kato, Jitsu; Suzuki, Takahiro

    Congenital unilateral absence of a pulmonary artery (UAPA) is a rare anomaly. Although there are several reports regarding pregnancy in patients with unilateral absence of a pulmonary artery, there are no case reports describing anesthesia for Cesarean section in a patient with unilateral absence of a pulmonary artery. We present a patient with unilateral absence of a pulmonary artery who underwent Cesarean sections twice at the ages of 24 and 26 years under spinal anesthesia for surgery and epidural analgesia for postoperative pain relief. Both times, spinal anesthesia and epidural analgesia enabled successful anesthesia management without the development of either pulmonary hypertension or right heart failure. Spinal anesthesia combined with epidural analgesia is a useful anesthetic method for a Cesarean section in patients with unilateral absence of a pulmonary artery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  6. Advanced pulmonary arterial hypertension: mechanical support and lung transplantation

    Directory of Open Access Journals (Sweden)

    Sonja Bartolome

    2017-12-01

    Full Text Available The development of targeted therapies has transformed the outlook for patients with pulmonary arterial hypertension (PAH; however, some patients fail to achieve an adequate clinical response despite receiving maximal treatment. For these patients, lung transplantation remains an important therapeutic option, and recommendations for transplantation are included in the current European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension. Although lung transplantation is not without risk, overall long-term survival rates are good and substantial improvements in quality of life have been reported for lung transplant recipients. In this review, we describe the important considerations prior to, during and after transplantation, including the role of mechanical support, in patients with advanced PAH.

  7. Pulmonary Arterial Capacitance Predicts Cardiac Events in Pulmonary Hypertension Due to Left Heart Disease.

    Directory of Open Access Journals (Sweden)

    Koichi Sugimoto

    Full Text Available Although pulmonary hypertension due to left heart disease (LHD-PH accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH.The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg. The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events.The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days. The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001. The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424-0.730, P < 0.001.PAC is useful in the prediction of cardiac event risk in LHD-PH patients.

  8. Down-Regulation of TRPM8 in Pulmonary Arteries of Pulmonary Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Xiao-Ru Liu

    2013-06-01

    Full Text Available Background: Pulmonary hypertension (PH is characterized by profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs. Multiple transient receptor potential melastatin-related (TRPM subtypes have been identified in vascular tissue. However, the changes in the expression and function of TRPM channels in pulmonary hypertension have not been characterized in detail. Methods: We examined the expression of TRPM channels and characterized the functions of the altered TRPM channels in two widely used rat models of chronic hypoxia (CH- and monocrotaline (MCT-induced PH. Results: CH-exposed and MCT-treated rats developed severe PH and right ventricular hypertrophy, with a significant decrease in TRPM8 mRNA and protein expression in pulmonary arteries (PAs. The downregulation of TRPM8 was associated with significant reduction in menthol-induced cation-influx. Time-profiles showed that TRPM8 down-regulation occurred prior to the increase of right ventricular systolic pressure (RVSP and right ventricular mass index (RVMI in CH-exposed rats, but these changes were delayed in MCT-treated rats. The TRPM8 agonist menthol induced vasorelaxation in phenylephrine-precontracted PAs, and the vasorelaxing effects were significantly attenuated in PAs of both PH rat models, consistent with decreased TRPM8 expression. Conclusion: Downregulation of TRPM8 may contribute to the enhanced vasoreactivity in PH.

  9. Right ventricle to pulmonary artery connection: Evolution and current alternatives

    Directory of Open Access Journals (Sweden)

    Alsayed Mahmoud Salem

    2016-05-01

    Full Text Available Despite the introduction of different right ventricle to pulmonary artery reconstructive techniques and conduits, the ideal option is yet to be developed. Valved conduits mimicking the natural right ventricular outflow, however, they do not grow and re-operation for conduit replacement is inevitable. So, surgeons have constantly tried to evolve surgical techniques that would obviate their use and allow age-related growth. We tried to review the evolution of these techniques and the current status of these alternatives focusing on their suitability for variable age groups and different pathological entities.

  10. Protein losing enteropathy secondary to a pulmonary artery stent

    Directory of Open Access Journals (Sweden)

    Narayanswami Sreeram

    2012-01-01

    Full Text Available A 2-year-old patient with hypoplastic left heart syndrome presented 6 months following Fontan completion with protein-losing enteropathy (PLE. He had undergone stent implantation in the left pulmonary artery after the Norwood procedure, followed by redilation of the stent prior to Fontan completion. Combined bronchoscopic and catheterization studies during spontaneous breathing confirmed left bronchial stenosis behind the stent, and diastolic systemic ventricular pressure during expiration of 25 mm Hg. We postulate that the stent acts as a valve, against which the patient generates high expiratory pressures, which are reflected in the ventricular diastolic pressure. This may be the cause of PLE.

  11. The study of risk in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gerald Simonneau

    2012-09-01

    Full Text Available A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH. The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1 clinical decision-making; 2 policy and reimbursement; and 3 future trials and research.

  12. Canine pulmonary vein-to-pulmonary artery ratio: echocardiographic technique and reference intervals.

    Science.gov (United States)

    Birettoni, F; Caivano, D; Patata, V; Moïse, N S; Guglielmini, C; Rishniw, M; Porciello, F

    2016-12-01

    The size of the pulmonary veins (PVs) and pulmonary arteries (PAs) changes in response to hemodynamic alterations caused by physiological events and disease. We sought to create standardized echocardiographic methods for imaging the right ostium of the pulmonary veins (RPVs) and the right pulmonary artery (RPA) using specific landmarks and timing to quantify vessel diameters and phasic changes during the cardiac cycle. Fifty client-owned healthy dogs prospectively recruited. M-mode and 2-dimensional images were obtained from modified right parasternal long and short axis views. Right ostium of the pulmonary veins and RPA measurements were timed with electrical [peak of the QRS complex (RPVQRS and RPAQRS) and end of T wave (RPVT and RPAT)] or mechanical events [RPV and RPA vessels at their respective maximal (RPVMAX; RPAMAX) and minimal (RPVMIN; RPAMIN) diameters]. Right ostium of the pulmonary veins and RPA measurements were also indexed to the aorta. In normal dogs regardless of the echocardiographic view or time in the cardiac cycle, the RPV/RPA ratio approximated 1.0. Mechanically timed fractional changes (distensibility indices) in RPV and RPA diameters did not differ (p=0.99; 36.9% and 36.8%, respectively). ECG-timed fractional changes (distensibility indices) in RPV and RPA diameter were at least 50% smaller than mechanically timed changes (p<0.05). RPV:Ao and RPA:Ao ranged between 0.3 and 0.6, with lower values obtained in diastole and larger values in systole (p<0.0001). Multiple positive and negative deflections were identified on the RPV and RPA M-mode tracings. This study provides detailed methodology and 2D and M-mode reference intervals for the RPV and RPA dimensions and the phasic changes during the cardiac cycle of the dog using echocardiography. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Noninvasive Doppler tissue measurement of pulmonary artery compliance in children with pulmonary hypertension.

    Science.gov (United States)

    Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

    2006-04-01

    We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Dynamic compliance (C(dyn)) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. C(dyn) was calculated as: [(D(s) - D(d))/(D(d) x P(s))] x 10(4); where D(s) = systolic diameter, D(d) = diastolic diameter, and P(s) = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. C(dyn) was also measured in an additional 13 patients undergoing reactivity studies. Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, C(dyn) calculated by CMM DTI agreed with C(dyn) calculated using invasive techniques (23.4 +/- 16.8 vs 29.1 +/- 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower C(dyn) values than control subjects (P < .01). C(dyn) values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress-strain behavior of these arteries. Reactivity in C(dyn) agreed with reactivity measured using impedance techniques. The C(dyn) method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension.

  14. Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters

    Directory of Open Access Journals (Sweden)

    Yang Ting

    2010-03-01

    Full Text Available Abstract Background Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH in chronic obstructive pulmonary disease (COPD. Chymase has been shown to function in the enzymatic production of angiotensin II (AngII and the activation of transforming growth factor (TGF-β1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Methods Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. Results Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-β1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE activity in hamster lungs. Conclusions These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-β1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.

  15. Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome.

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    Fei Yang

    Full Text Available Pulmonary arterial hypertension, also known as Ascites syndrome (AS, remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear.We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes pathways (Padj<0.05 regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group.Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression.

  16. Acute pulmonary edema following inflation of arterial tourniquet.

    Science.gov (United States)

    Santhosh, M C B; Pai, R B; Rao, R P

    2014-10-01

    Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  17. Fetal pulmonary and cerebral artery Doppler velocumetry in normal and high risk pregnancy.

    Science.gov (United States)

    Breborowicz, Andrzej; Dubiel, Mariusz; Pietryga, Marek; Breborowicz, Grzegorz H; Gudmundsson, Saemundur

    2014-01-01

    Studies on fetal lung/brain circulation by means of power Doppler technique have suggested a marked reduction in lung perfusion in high-risk pregnancies as a sign of circulation redistribution. The ratio between lung/brain perfusion might therefore give a new method to predict fetal circulation centralization. The aim of the present study was to obtain fetal lung and cerebral artery ratio in normal and high-risk pregnancies. Doppler samples from proximal right pulmonary artery blood velocities and middle cerebral artery (MCA) were recorded cross-sectionally in 228 normal singleton pregnancies at gestational age 22 to 40 weeks. MCA/right pulmonary artery pulsatility index (PI) ratio was calculated. Doppler samples from proximal right pulmonary artery and MCA were also recorded in 89 high-risk singleton pregnancies and the results related to perinatal outcome. In the normal controls, right pulmonary artery PI remained stable until 30 weeks of gestation with slight increase thereafter until term. The MCA to right pulmonary artery PI ratio increased between 22 and 28 weeks of gestation with the rapid fall towards term. In the high-risk pregnancies group, right pulmonary artery PI showed no significant correlation to perinatal outcome, but signs of brain-sparing in the MCA were correlated to all adverse outcome parameters. Velocimetry of the middle cerebral artery is better than velocimetry of right pulmonary artery in predicting adverse outcome of pregnancy The brain/lung PI ratio does not improve the prediction of adverse outcome of pregnancy.

  18. Anomalous left coronary artery from the pulmonary artery presenting with aborted sudden death in an octogenarian: a case report

    Directory of Open Access Journals (Sweden)

    Separham Ahmad

    2012-01-01

    Full Text Available Abstract Introduction We report a rare coronary anomaly presenting with aborted sudden death in an octogenarian. An anomalous left coronary artery from the pulmonary artery is a rare coronary anomaly which usually presents in the first year of life. Survival into adulthood and the elderly years is extremely rare. Case presentation An 85-year-old Caucasian woman was brought to our hospital following cardiopulmonary arrest. After prolonged resuscitation and stabilization of our patient, further evaluation revealed an anomalous left coronary artery from pulmonary artery syndrome. She was discharged on medication. Conclusion An anomalous left coronary artery from the pulmonary artery can present in elderly and even octogenarian patients. Careful history, physical examination and an appropriate invasive study are needed to confirm the diagnosis.

  19. Separate pulmonary artery and vein magnetic resonance angiography by use of an arterial spin labeling method.

    Science.gov (United States)

    Okuaki, Tomoyuki; Ishimoto, Tsuyoshi; Miyati, Tosiaki; Kobayashi, Satoshi; Ishihara, Masaru; Kawakami, Momoe; Ogino, Tetsuo; Van Cauteren, Marc

    2014-07-01

    A separate pulmonary vein (PV) is difficult to depict with the commonly used bright-blood magnetic resonance angiography method. Until now, no study has described the depiction of peripheral PVs without the artery. Our purpose in this study was to develop an arterial spin labeling (ASL)-based magnetic resonance angiography sequence to depict the pulmonary artery (PA) and vein separately. We developed such a sequence by using two inversion recovery pulses. The first pulse was non-selective, and the second pulse was selective and was applied to the aorta and heart. All studies were conducted on a 1.5-T clinical magnetic resonance system with six different inversion times for seven healthy volunteers. For evaluation, we categorized the inversion times by using visual scoring. Then, we used the magnitude image to evaluate the PA, and we used the real image to evaluate the PV. For the PA, an inversion time of 300 ms had the lowest score (1.43), and the score changed with increasing times; an inversion time of 1,100 ms had the highest score (3.85). For the PV, an inversion time of 300 ms had the highest score (2.68), and the score decreased with increasing times. The results indicated that the PA and vein could be depicted separately by the use of an ASL-based magnetic resonance angiography method. The optimal inversion times for the PV and artery were 300 and 1,100 ms, respectively.

  20. How to prevent echocardiographic misinterpretation of Gerbode type defect as pulmonary arterial hypertension.

    Science.gov (United States)

    Tehrani, Faramarz; Movahed, Mohammad-Reza

    2007-12-01

    We present a rare case of left ventricular to right atrial communication, a Gerbode type defect discovered in an adult female, originally misinterpreted as pulmonary arterial hypertension. The case report will be followed by the review of the literature and a discussion about how to prevent echocardiographic misinterpretation of this defect as pulmonary arterial hypertension using careful echocardiographic examination.

  1. Pediatric pulmonary arterial hypertension : Towards optimal classification, treatment strategies and outcome

    NARCIS (Netherlands)

    Zijlstra, Willemijn

    2017-01-01

    Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the small pulmonary arteries and has a poor prognosis. Median survival of children with PAH is <3 years if untreated. The development of PAH-targeted drugs and the introduction of evidence-based treatment guidelines have greatly

  2. The compliance of the porcine pulmonary artery depends on pressure and heart rate

    NARCIS (Netherlands)

    L. Kornet (Lilian); J.R.C. Jansen (Jos); F.C.A.M. te Nijenhuis (Frances); G.J. Langewouters; A. Versprille (Adrian)

    1998-01-01

    textabstract1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the

  3. The compliance of the porcine pulmonary artery depends on pressure and heart rate

    NARCIS (Netherlands)

    Kornet, L.; Jansen, J.R.C.; Nijenhuis, F.C.A.M. te; Langewouters, G.J.; Versprille, A.

    1998-01-01

    1. The influence of mean pulmonary arterial pressure (mean P(pa)) on dynamic (C(d)) and pseudostatic compliance (C(ps)) of the pulmonary artery was studied at a constant and a changing heart rate. C(d) is the change in cross-sectional area (CSA) relative to the change in P(pa) throughout a heart

  4. Clinical impact of balloon angioplasty for branch pulmonary arterial stenosis.

    Science.gov (United States)

    Hosking, M C; Thomaidis, C; Hamilton, R; Burrows, P E; Freedom, R M; Benson, L N

    1992-06-01

    The clinical impact of percutaneous balloon angioplasty on the management of patients with native or postoperative pulmonary arterial stenosis was reviewed. Seventy-four patients underwent 110 angioplasty procedures. Mean age at dilation was 6.7 +/- 5.3 years (range 0.2 to 18.1), 17 patients were aged less than 1 year, mean follow-up was 37.7 +/- 22.8 months (range 16 to 96), and 34 patients (44%) had follow-up angiography. Pulmonary artery dilation was acutely successful in 53% of patients, 17% had recurrent stenosis, and 5% had complications. The impact on subsequent care was favorably influenced in 26 of 74 patients (35%) with either complete resolution of stenosis (n = 7), optimizing future surgical conditions (n = 14), reduction in right ventricular pressure by greater than 20% (n = 3), or improvement of ipsilateral lung perfusion (n = 2). No patient previously considered inoperable was subsequently considered suitable for surgical repair owing to the intervention. No correlation was found between success and cardiac diagnosis (p = 0.48), site of stenosis (p = 0.78), balloon-vessel ratio (p = 0.42), or whether the stenotic area consisted of native or synthetic material (p = 0.22). No predictive factors for success could be defined, and often there was only a transient clinical impact. Due to the low complication risk and potential for a beneficial result, it still appears prudent to offer angioplasty as an initial therapeutic modality in this setting.

  5. Effects of different pulmonary vasodilators on arterial saturation in a model of pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Eva Maria Becker

    Full Text Available BACKGROUND: Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH, probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. METHODS: We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6 of anesthetized minipigs (7 weeks, 4 to 5 kg BW, and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only, endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg, phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg, and soluble guanylate cyclase stimulators (BAY 41-8543 and riociguat; 1, 3, 10, 30 µg/kg. Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. RESULTS: Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect. Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41-8543 lowered arterial oxygen saturation of hemoglobin the least. CONCLUSIONS: Future investigations will be required to confirm these findings in clinical settings.

  6. Pulmonary arterial hypertension associated with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Michele D'Alto

    2012-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a common complication of congenital heart disease (CHD, with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD. The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH-CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges. This article gives an overview of the demographics, pathophysiology and treatment of PAH-CHD and focuses on individuals with Down's syndrome as an important and challenging patient group.

  7. Screening for pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2009-09-01

    Full Text Available The onset and progression of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc can be particularly aggressive; however, effective treatments are available. Therefore, early identification of patients with suspected PAH, confirmation of diagnosis, and intervention is essential. PAH may be challenging to diagnose in its earliest stages, particularly in populations that have multiple causes of breathlessness, and, therefore, screening is required. The optimal screening tools and methodology are, as yet, unknown, and this is confounded by a lack of consensus over which patients to screen. Current practice favours annual screening of all SSc patients using Doppler echocardiography to detect elevated right heart pressures. This will typically identify most patients with the various forms of pulmonary hypertension found in SSc. The optimum thresholds for Doppler echocardiography are still subject to investigation, especially for patients with mild pulmonary hypertension, and this technique may, therefore, yield a significant number of false-positives and a currently unknown number of false-negatives. Confirmatory right heart catheterisation remains necessary in all suspected cases. Further research is needed to identify the optimal tools and the screening approach with greatest specificity and selectivity.

  8. Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Hsu, Steven; Houston, Brian A.; Tampakakis, Emmanouil; Bacher, Anita C.; Rhodes, Parker S.; Mathai, Stephen C.; Damico, Rachel L.; Kolb, Todd M.; Hummers, Laura K.; Shah, Ami A.; McMahan, Zsuzsanna; Corona-Villalobos, Celia P.; Zimmerman, Stefan L.; Wigley, Fredrick M.; Hassoun, Paul M.; Kass, David A.; Tedford, Ryan J.

    2016-01-01

    Background Right ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis as compared to idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients. Methods and Results RV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; p=0.039). At matched exercise (25 Watts), SSc-PAH patients failed to augment contractility (end-systolic elastance) whereas IPAH did (p<0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, p=0.004, and +19±4% versus −1±6%, p<0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort. Conclusions RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients. PMID:27169739

  9. [Tetralogy of Fallot with anomalous origin of unilateral pulmonary artery].

    Science.gov (United States)

    Endo, M; Haneda, K; Suzuki, Y; Mohri, H; Yamaki, S

    1991-02-01

    Between 1971 and 1988, 7 patients (pts) of TOF with anomalous origin of unilateral pulmonary artery (AOPA) underwent intracardiac repair at Tohoku University Hospital. They were 2 males and 5 females, with ages ranging from 4 to 26 years old. The right PA originated from the RV in all cases, whereas the left PA originated from the ascending aorta in 2 pts (Group 1) and from the ductus arteriosus in 5 pts (Group 2 & 3). In Group 2 (2 pts), the left PA was separated from the right PA with intraluminal membrane. In Group 3 (3 pts), there was no communication between both pulmonary arteries. The left PA was reconstructed in Group 1 & 2. However, it was impossible to reconstruct the left PA in Group 3 since the ductus arteriosus and left PA had been occluded before intracardiac repair. In Group 3, VSD was closed with one-way (RV----LV) valved patch for the aim of lowering RV pressure. Postoperative RV/Ao pressure ratio was 0.5-0.8 in the cases of Group 1 & 2, 0.8-1.0 in Group 3. Three patients (one in each group) died postoperatively due to low output syndrome. Autopsy revealed pulmonary vascular obstructive disease (PVOD) of the left lung in Group 1. It is concluded that TOF with AOPA should be corrected before the advance of PVOD in case PA originate from the ascending aorta, and before the occlusion of the ductus in case PA originate from it, in order to prevent postoperative RV overload.

  10. 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 (H 2 S) 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+H 2 S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H 2 S, and H 2 S. 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 H 2 S 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 H 2 S/CSE pathway was downregulated in MCT rats. By contrast, an H 2 S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H 2 S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H 2 S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H 2 S attenuated endothelial inflammation by inhibiting the NF-κB pathway.

  11. 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 the...

  12. Change of extracellular signal-regulated kinase expression in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease.

    Science.gov (United States)

    Liu, Kui; Liu, Xian-Sheng; Yu, Mu-Qing; Xu, Yong-Jian

    2013-01-01

    Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease (COPD) by resulting in pulmonary vascular remodeling that involves pulmonary artery smooth muscle cell (PASMC) proliferation. However, the molecular mechanism underlying this process remains poorly understood. The purpose of this study was to investigate the role of extracellular signal-regulated kinase (ERK) in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate COPD. The peripheral lung tissues were obtained from 14 nonsmokers with normal lung function, 18 smokers with normal lung function, and 16 smokers with mild to moderate COPD. The morphological changes of pulmonary arteries were observed by hematoxylin-eosin (HE) staining. Primary cultured human pulmonary artery smooth muscle cells (HPASMCs) were exposed to cigarette smoke extract (CSE). Cell proliferation was determined by cell counting and Methyl thiazolyl tetrazolium assay. Protein expression was analyzed by western blotting. Morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than that in nonsmoker group (P < .01). The protein level of ERK was significantly increased in smoker group and COPD group as compared with nonsmoker group (P < .01). The expression of ERK was significantly increased in HPASMCs at protein levels when HPASMCs were treated with 5% CSE (P < .01), which significantly promoted the proliferation of HPASMCs (P < .01). Increased expression of ERK might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with and without COPD.

  13. A mycotic pulmonary artery aneurysm associated with candida endocarditis: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Jin Il; Lee, Ji Won; Jeong, Yeon Joo; Song, Seung Hwan [Pusan National University School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

    2014-03-15

    We report a case of a mycotic pulmonary aneurysm associated with Candida endocarditis in a 53-year-old male with lymphoma. The initial diagnosis was a pulmonary artery aneurysm attributable to vasculitis, such as that associated with Behcet's disease, but a mycotic pulmonary artery aneurysm was later considered as a differential diagnosis. Identification of valve vegetation on the chest CT was helpful in this regard. We review the literature on the disease etiology, radiological findings, and management options.

  14. Pulmonary atresia and ventricular septal defect with collaterals to right lung associated with anomalous left pulmonary artery from the ascending aorta

    Energy Technology Data Exchange (ETDEWEB)

    Khositseth, Anant [Mahidol University, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok (Thailand); Siripornpitak, Suvipaporn; Pornkul, Ratanaporn [Mahidol University, Department of Radiology, Ramathibodi Hospital, Bangkok (Thailand)

    2010-12-15

    We present a 10-month-old boy with cyanosis. This is a rare case of pulmonary atresia, ventricular septal defect (VSD), major aorto-pulmonary collateral arteries (MAPCAs) to the right lung with absent native right pulmonary artery (RPA) in association with anomalous left pulmonary artery (LPA) from the ascending aorta (AAo). Echocardiography was unable to identify all of the cardiovascular abnormalities. Multidetector CT demonstrated all of these abnormalities and is the investigation of choice instead of cardiac catheterization. (orig.)

  15. [Central arterial pressure in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Gel'tser, B I; Brodskaia, T A

    2008-01-01

    To study central (aortic) arterial pressure (CAP) and aortic stiffness in patients with chronic obstructive pulmonary disease (COPD) of different severity. Non-invasive arteriography with Tensio Climo TL1 arteriograph (TensioMed, Hungary) was made to measure aortic stiffness and systolic pressure (SAP) in 54 COPD patients and 25 healthy controls. The difference between the central and peripheral SAP (delta SAP) and central/ peripheral pressure correspondence index (CI) were estimated. Indirect arteriography has found that patients with moderate and severe COPD have stable elevated central SAP which is close to brachial SAP while in healthy controls the difference between central and peripheral SAP is 10.2 +/- 2.1 mmHg. With progression of COPD severity, deltaSAP diminishes while CI rises showing growing disproportion between central and peripheral blood pressure. In severe COPD physiological difference between them disappears. In COPD increased CAP is associated with impaired mechanical properties of the arterial bed and myocardial contractility proved by significant links between CAP and left ventricular ejection fraction index and key parameters of arterial stiffness. Aortic CAP, delta SAP and CI are additional informative criteria of COPD severity and high cardiovascular risk as shown by their close correlation with hypoxemia, severity and duration of the disease.

  16. Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Francisca Gavilanes

    2014-12-01

    Full Text Available OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH. METHODS: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD, significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. RESULTS: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH was confirmed in 302 patients (78.6%. The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3% and 178 (81.7% were diagnosed with PH associated with LVD (PH-LVD and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001. CONCLUSIONS: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant.

  17. Pulmonary hyperinflation due to gas trapping and pulmonary artery size: The MESA COPD Study.

    Directory of Open Access Journals (Sweden)

    Hooman D Poor

    Full Text Available Pulmonary hypertension is associated with increased morbidity and mortality in chronic obstructive pulmonary disease (COPD. Since pulmonary artery (PA size increases in pulmonary hypertension, we measured PA cross-sectional area using magnetic resonance imaging (MRI to test the hypothesis that pulmonary hyperinflation due to gas trapping is associated with PA cross-sectional area in COPD.The MESA COPD Study recruited participants with COPD and controls from two population-based cohort studies ages 50-79 years with 10 or more pack-years and free of clinical cardiovascular disease. Body plethysmography was performed according to standard criteria. Cardiac MRI was performed at functional residual capacity to measure the cross-sectional area of the main PA. Percent emphysema was defined as the percentage of lung voxels less than -950 Hounsfield units as assessed via x-ray computed tomography. Analyses were adjusted for age, gender, height, weight, race-ethnicity, the forced expiratory volume in one second, smoking status, pack-years, lung function, oxygen saturation, blood pressure, left ventricular ejection fraction and percent emphysema.Among 106 participants, mean residual volume was 1.98±0.71 L and the mean PA cross-sectional area was 7.23±1.72 cm2. A one standard deviation increase in residual volume was independently associated with an increase in main PA cross-sectional area of 0.55 cm2 (95% CI 0.18 to 0.92; p = 0.003. In contrast, there was no evidence for an association with percent emphysema or total lung capacity.Increased residual volume was associated with a larger PA in COPD, suggesting that gas trapping may contribute to pulmonary hypertension in COPD.

  18. Mediastinal pulmonary artery is associated with greater artery diameter and lingular division volume.

    Science.gov (United States)

    Dejima, Hitoshi; Takahashi, Yusuke; Hato, Tai; Seto, Katsutoshi; Mizuno, Tetsuya; Kuroda, Hiroaki; Sakakura, Noriaki; Kawamura, Masafumi; Sakao, Yukinori

    2017-04-28

    Pulmonary vessels have numerous variation and aberrant branching patterns. Mediastinal lingular artery (MLA), the most common aberrant branch, might contribute to greater blood flow to lingular division. Hence, we investigated a correlation between lingular division volume and MLA using three-dimensional CT volumetry. We included 199 consecutive patients who underwent surveillance chest CT to detect possible malignancies in April 2015. We measured lingular division volume and cross-sectional area of lingular arteries using three-dimensional CT volumetry. MLA was identified in 58 cases (29.1%). The MLA group had significantly greater lingular division volume (median ± quartile deviation: 378.3 ± 75.5 mL vs. 330.0 ± 87.5 mL; p = 0.021) and percentage lingular division to left lung volume (19.0 ± 2.62% vs. 16.6 ± 2.39%; p MLA group. Total cross-sectional area of lingular arteries of the MLA group was significantly larger than that of the non-MLA group (46.1 ± 9.46 vs. 40.2 ± 5.76 mm2; p = 0.003). The total cross-sectional area of the lingular arteries strongly correlated to the percentage of lingular division to left lung volume (r = 0.689, p < 0.001). This is the first report demonstrating a positive correlation between branching pattern of pulmonary artery and lung volume.

  19. Hybrid pulmonary artery plication followed by transcatheter pulmonary valve replacement: Comparison with surgical PVR.

    Science.gov (United States)

    Sosnowski, Cyndi; Matella, Thomas; Fogg, Louis; Ilbawi, Michel; Nagaraj, Hosakote; Kavinsky, Clifford; Wolf, Andrew R; Diab, Karim; Caputo, Massimo; Kenny, Damien

    2016-11-01

    Objective/Background Historically, the sole option for patients with a dysfunctional native right ventricular outflow tract (RVOT) requiring re-establishment of pulmonary competence has been surgical PVR. We sought to compare early outcomes of hybrid pulmonary valve replacement (PVR) combining surgical plication of the main pulmonary artery followed by transcatheter PVR, with a contemporary cohort of surgical PVR patients. Methods Retrospective chart analysis of all patients with a dilated native RVOT eligible for surgical PVR over 36 months was performed. The cohorts included patients with previous tetralogy of Fallot repair (n = 14), and previous intervention for congenital abnormality of the pulmonary valve (n = 7). Results Twenty-one patients with a dysfunctional native RVOT met criteria for PVR; 8 using the hybrid procedure (group 1: age, 31.5 +/- 17.4 years) and 13 with cardiopulmonary bypass (CPB) (group 2: age, 31 +/- 18.4 years). Valve delivery was successful in all patients with no procedural mortality. Group 1 had a lesser requirement for blood products (P =hybrid PVR following RVOT plication provides a reasonable alternative to surgical PVR particularly in higher risk cohorts, reducing possible longer-term consequences of repeated runs of CPB. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Automated 3D Volumetry of the Pulmonary Arteries based on Magnetic Resonance Angiography Has Potential for Predicting Pulmonary Hypertension.

    Directory of Open Access Journals (Sweden)

    Fabian Rengier

    Full Text Available To demonstrate feasibility of automated 3D volumetry of central pulmonary arteries based on magnetic resonance angiography (MRA, to assess pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and to investigate the potential of the technique for predicting pulmonary hypertension.MRA of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls. 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries (MPA, RPA and LPA. Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA. For comparison, diameters were also manually measured on axial reconstructions and double oblique multiplanar reformations. Analyses were performed by two cardiovascular radiologists, and by one radiologist again after 6 months.Mean volumes of MPA, RPA and LPA for patients/controls were 5508 ± 1236/3438 ± 749, 3522 ± 934/1664 ± 468 and 3093 ± 692/1812 ± 474 μl/(cm length x m2 BSA (all p<0.001. Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls (all p<0.001. Intra- and interobserver agreement were excellent for both volume and diameter measurements using 3D segmentation (intraclass correlation coefficients 0.971-0.999, p<0.001. Area under the curve for predicting pulmonary hypertension using volume was 0.998 (95% confidence interval 0.990-1.0, p<0.001, compared to 0.967 using manually measured MPA diameter (95% confidence interval 0.910-1.0, p<0.001.Automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery volume may serve as a superior

  1. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Deng, Wei [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072 (China); Han, Hui; Wang, Hao [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Chen, Yuguo [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Li, Yu, E-mail: qlliyu@126.com [Department of Respiratory, Qilu Hospital of Shandong University, Jinan 250012 (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  2. Concomitant Deep Venous Thrombosis, Femoral Artery Thrombosis, and Pulmonary Embolism after Air Travel

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    Salim Abunnaja

    2014-01-01

    Full Text Available The association between air travel and deep venous thrombosis and/or pulmonary embolism “economy-class syndrome” is well described. However, this syndrome does not describe any association between long duration travel and arterial thrombosis or coexistence of venous and arterial thrombosis. We present a case of concomitant deep venous thrombosis, acute femoral artery thrombosis, and bilateral pulmonary embolisms in a patient following commercial air travel. Echocardiogram did not reveal an intracardiac shunt that may have contributed to the acute arterial occlusion from a paradoxical embolus. To our knowledge, this is the first report in the literature that associates air traveling with both arterial and venous thrombosis.

  3. Pulmonary Artery Endothelial Cell Phenotypic Alterations in a Large Animal Model of Pulmonary Arteriovenous Malformations Following the Glenn Shunt

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    Kavarana, Minoo N.; Mukherjee, Rupak; Eckhouse, Shaina R.; Rawls, William F.; Logdon, Christina; Stroud, Robert E.; Patel, Risha K.; Nadeau, Elizabeth K.; Spinale, Francis G.; Graham, Eric M.; Forbus, Geoffrey A.; Bradley, Scott M.; Ikonomidis, John S.; Jones, Jeffrey A.

    2014-01-01

    Background: Longevity of the superior cavopulmonary connection (SCPC) is limited by the development of pulmonary arteriovenous malformations (PAVM). The goal of this study was to determine whether phenotypic changes in pulmonary artery endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation. Methods: A superior vena cava to right pulmonary artery connection was constructed in 5 pigs. Pulmonary arteries were harvested at 6-8 weeks following surgery to establish cultures of PAEC and smooth muscle cells, to determine cell proliferation, gene expression, and tubule formation. Abundance of proteins related to angiogenesis was measured in lung tissue. Results: Contrast echocardiography revealed right-to-left shunting, consistent with PAVM formation. While the proliferation of smooth muscle cells from the right pulmonary artery (RPA) (shunted side) and left pulmonary artery (LPA) (non- shunted side) were similar, right PAEC proliferation was significantly higher. Expression profiles of genes encoding cellular signaling proteins were higher in PAECs from the RPA vs. LPA. Protein abundance of angiopoietin-1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both pSCPC. This study found that PAVM development occurred concomitantly with differential changes in PAEC proliferative ability and phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2 complex in the right lung, which may provide novel therapeutic targets to attenuate PAVM formation following a SCPC. PMID:23968766

  4. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension

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    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E.; Arons, Elena; Zaman, Paula; Polach, Kevin J.; Matar, Majed; Yung, Lai-Ming; Yu, Paul B.; Bowman, Frederick P.; Opotowsky, Alexander R.; Waxman, Aaron B.; Loscalzo, Joseph; Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10−9 to 10−7 M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor–small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro. Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo. Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.—Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery

  5. Aborted sudden cardiac death in a young male with anomalous left coronary artery arising from the pulmonary artery

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    Chih-Han Huang

    2017-01-01

    Full Text Available Anomalous left coronary artery arising from the pulmonary artery (ALCAPA is a rare type of congenital coronary abnormality that may be associated with early infant mortality and sudden adult cardiac death. We report a case regarding a 23-year-old male who collapsed during a marathon race and was resuscitated with cardiopulmonary resuscitation. Subsequent workups verified the diagnosis of ALCAPA. The patient underwent surgical intervention with obliteration of the ALCAPA orifice and coronary artery bypass grafting with left internal mammary artery to left anterior descending coronary artery. The procedure was done smoothly, and he was discharged uneventfully.

  6. Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

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    Rachel D. Torok MD

    2017-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI. We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

  7. Extrinsic airway compression secondary to pulmonary arterial conduits: MR findings

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    Donnelly, L.F. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States); Strife, J.L. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States); Bailey, W.W. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States)

    1997-03-01

    Abnormal enlargement or malposition of any vascular structure or mass adjacent to the airway can cause extrinsic airway compression. In children with previous surgery for congenitial heart disease, mass effect from prosthetic devices or alteration in the anatomic position of normal structures can lead to extrinsic airway compression. Because many children have complex medical problems after cardiac surgery, wheezing may be attributed to cardiac causes and airway compression may not be investigated. Furthermore, the distal airway compression seen in these children often is not visualized on chest radiographys. MR imaging can be useful in evaluating extrinsic airway compression in these patients. We present the MR imaging of two patients with symptomatic extrinsic airway compression secondary to pulmonary arterial conduits. (orig.)

  8. Mazindol: a risk factor for pulmonary arterial hypertension?

    Science.gov (United States)

    Konofal, Eric; Benzouid, Cherine; Delclaux, Christophe; Lecendreux, Michel; Hussey, Elizabeth

    2017-06-01

    Mazindol is an imidazo-isoindole derivative, a tricyclic compound and a non-amphetamine central nervous system stimulant that blocks dopamine and norepinephrine reuptake. Mazindol was withdrawn from the US and European markets in 1999 for reasons unrelated to its efficacy or safety around a time when other anorexic drugs were found to be associated with the development of pulmonary arterial hypertension (PAH). Despite the use of mazindol for decades, reports of PAH due to mazindol intake have been extremely rare. Recent interest on mazindol has emerged for the treatment of narcolepsy and attention-deficit/hyperactivity disorder. Therefore, an updated understanding of the potential benefits and risks of mazindol in these patient populations is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy

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    Hardin EA

    2016-11-01

    Full Text Available Elizabeth Ashley Hardin,1 Kelly M Chin2 1Department of Internal Medicine, Division of Cardiology, 2Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. Keywords: selexipag, pulmonary arterial hypertension, prostacyclin

  10. Pulmonary artery aneurysm with patent arterial duct: resection of aneurysm and ductal division.

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    Tefera, Endale; Teodori, Michael

    2013-10-01

    Congenital or acquired aneurysm of the pulmonary artery (PA) is rare. Although aneurysms are described following surgical treatment of patent ductus arteriosus (PDA), occurrence of this lesion in association with PDA without previous surgery is extremely uncommon. An eight-year-old patient with PDA and aneurysm of the main PA is described in this report. Clinical diagnosis of PDA was made upon presentation. Diagnosis of PA aneurysm was suspected on chest x-ray and was confirmed on transthoracic echocardiography. Successful surgical resection of the aneurysm and division of the duct were performed under cardiopulmonary bypass. The patient did well on follow-up both from clinical and echocardiographic point of view.

  11. Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery?

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    Ujjwal Kumar Chowdhury

    2016-01-01

    Full Text Available We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting.

  12. Epoprostenol sodium for treatment of pulmonary arterial hypertension

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    Saito Y

    2015-05-01

    Full Text Available Yukihiro Saito,1 Kazufumi Nakamura,1 Satoshi Akagi,1 Toshihiro Sarashina,1 Kentaro Ejiri,1 Aya Miura,1 Aiko Ogawa,2 Hiromi Matsubara,2 Hiroshi Ito1 1Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Division of Cardiology, National Hospital Organization Okayama Medical Center, Okayama, Japan Abstract: The release of endogenous prostacyclin (PGI2 is depressed in patients with pulmonary arterial hypertension (PAH. PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. Keywords: pulmonary arterial hypertension, prostacyclin, apoptosis

  13. A review of pulmonary arterial hypertension: role of ambrisentan

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    Robyn J Barst

    2007-03-01

    Full Text Available Robyn J BarstColumbia University College of Physicians & Surgeons, New York, NY, USAAbstract: Pulmonary arterial hypertension (PAH is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ETA] and/or type-B [ETB] on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ETA-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5–10 mg orally once-daily improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ETA/ETB ERA, bosentan, and the ETA-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug–drug interactions support the role of ambrisentan for the treatment of PAH.Keywords: endothelin receptor antagonist, pulmonary arterial hypertension, endothelin-1, time to clinical worsening, Borg dyspnea index

  14. Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

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    da Silva Gonçalves Bos, Denielli; Van Der Bruggen, Cathelijne E; Kurakula, Kondababu; Sun, Xiao-Qing; Casali, Karina R; Casali, Adenauer G; Rol, Nina; Szulcek, Robert; Dos Remedios, Cris; Guignabert, Christophe; Tu, Ly; Dorfmuller, Peter; Humbert, Marc; Wijnker, Paul J M; Kuster, Diederik W D; van der Velden, Jolanda; Goumans, Marie-José; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; de Man, Frances S; Handoko, M Louis

    2017-11-22

    Background -Beneficial effects of parasympathetic stimulation have been reported in left heart failure, however, whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in PAH-patients, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase (AchE) inhibition, in experimental pulmonary hypertension (PH). Methods -Heart rate recovery (HRR) after maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction (RVEF) was assessed in 112 PAH-patients. Expression of nicotinic (α-7nAchR) and muscarinic (m2AchR) receptors, and AchE activity were evaluated in RV (n=11) and lungs (n=7) from PAH-patients undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg/day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg; s.c.) injection followed by 4 weeks of hypoxia. In a subgroup sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomized to vehicle or treatment (both n=12). At the end-of-study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological and protein analyses. Results -PAH-patients with lower RVEF (<41%) had a significantly reduced HRR in comparison to patients with higher RVEF. In PAH RV-samples, α-7nAchR was increased and AchE activity was reduced versus controls. No difference in m2AchR expression was observed. Chronic PYR-treatment in PH-rats normalized the cardiovascular autonomic function, demonstrated by an increase in parasympathetic activity and baroreflex sensitivity. PYR improved survival, increased RV

  15. Cytotoxic cells and granulysin in pulmonary arterial hypertension and pulmonary veno-occlusive disease.

    Science.gov (United States)

    Perros, Frédéric; Cohen-Kaminsky, Sylvia; Gambaryan, Natalia; Girerd, Barbara; Raymond, Nicolas; Klingelschmitt, Isabelle; Huertas, Alice; Mercier, Olaf; Fadel, Elie; Simonneau, Gerald; Humbert, Marc; Dorfmüller, Peter; Montani, David

    2013-01-15

    Pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) both display occlusive remodeling of the pulmonary vasculature responsible for increased pulmonary vascular resistances. Cytotoxic T (CTL), natural killer (NK), and natural killer T (NKT) cells play a critical role in vascular remodeling in different physiological and pathological conditions. Granulysin (GNLY) represents a powerful effector protein for all these subpopulations. To analyze the cytolytic compartment of inflammatory cells in patients with PAH and PVOD. The overall functional status of the cytolytic compartment was studied through epigenetic analysis of the GNLY gene in explanted lungs and in peripheral blood mononuclear cells. Flow cytometry technology allowed analysis of specific circulating cytolytic cells and GNLY contents. A GNLY-specific ELISA allowed measurement of GNLY serum concentrations. A decrease in GNLY demethylation in the gDNA extracted from peripheral blood mononuclear cells and explanted lungs was found specifically in PVOD but not in PAH. This was associated with a decrease in populations and subpopulations of CTL and NKT and an increase of NK populations. Despite the reduced granulysin-containing cells in patients with PVOD, GNLY serum levels were higher, suggesting these cells were wasting their content. Furthermore, the increase of GNLY concentration in the serum of PVOD was significantly higher than in patients with PAH. PVOD is characterized by alterations of circulating cytotoxic cell subpopulations and by epigenetic dysregulation within the GNLY gene. Our findings may be helpful in the quest to develop needed diagnostic tools, including flow cytometry analyses, to screen for suspected PVOD in patients with pulmonary hypertension.

  16. 53. Bilateral ductal stenting for nonconfluent pulmonary arteries in a newborn

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    K. Al Dhahri

    2016-07-01

    Full Text Available Bilateral PDA dependent pulmonary circulation with right and left pulmonary artery discontinuity is very rare. Limited data available for bilateral PDA stenting. Bilateral PDA stenting in nonconfluent pulmonary arteries is challenging procedure but can be considered as an option in the management of complex conditions like this. 12 days old Preterm (36 weeks gestation male baby with birth weight of 2.6 kg developed respiratory distress with severe cyanosis and desaturation upto 50%. Baby was intubated and started on Prostaglandin 0.05 mic/kg/mt. His saturation improved to 80%. Echocardiogram showed complex cyanotic heart disease, Situs ambiguous, dextrocardia, complete unbalanced AV septal defect, pulmonary atresia , nonconfluent small branch pulmonary arteries supplied by the bilateral patent ductus arteriosus (PDA from right aortic arch and all four pulmonary veins form a confluence and drain into superior vena cava(SVC through vertical vein with no obstruction. Baby was taken up for PDA stenting. descending aortogram showed right aortic arch with vertical tortuous duct to right pulmonary artery (RPA and another short duct with acute angle from left subclavian artery to left pulmonary artery (LPA . Both ducti stented with coronary stents. Vertical vein angiogram showed both lungs drain to a confluence and then to SVC via ascending vertical vein with no obstruction. After stenting lung perfusion improved and the baby was stable and maintained 80% saturation on room air. Bilateral PDA dependent pulmonary circulation with right and left pulmonary artery discontinuity is very rare. Our case is unique with Heterotaxy, TAPVC, Dextrocardia and double ducti. Eventhough bilateral ductal stenting is technically challenging it is successful through femoral artery approach.

  17. Medical image of the week: idiopathic pulmonary artery hypertension

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    Bernardo RJ

    2014-08-01

    Full Text Available No abstract available. Article truncated at 150 words. A 39-year-old woman presented to the clinic with a history of progressive shortness of breath of 6-month duration associated with bilateral lower extremity edema, fatigue, lightheadedness, palpitations and occasional substernal chest pain. Her past medical history was unremarkable other than mild anemia. On physical exam her respiratory rate was 20 breaths per minute and O2 saturation 94% on room air by pulse oximetry. There was jugular venous distention at 12 cm, 2+ bilateral lower extremity edema, a 5/6 systolic murmur over the left sternal border with a sternal heave. Labwork was unremarkable except for an elevated BNP 657 (normal value < 100 pg/mL. EKG (Figure 1 showed sinus rhythm with right bundle branch block. A 2-view chest X-ray (Figure 2 showed an enlarged right ventricle as well as dilated pulmonary arteries with no parenchymal infiltrates. CT angiography confirmed CXR findings (Figure 3 and was negative for pulmonary embolism. A 2D ...

  18. Combination therapy in the management of pulmonary arterial hypertension.

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    Buckley, M S; Staib, R L; Wicks, L M

    2013-05-01

    Pulmonary arterial hypertension (PAH) is a progressive disease without a cure, which can lead to right heart failure and death. Over the past decades, several therapeutic advances have been developed for the management of PAH. Although these agents have demonstrated clinical safety and efficacy, some patients may require additional drug therapy due to a lack of response or disease progression. The purpose of this review was to evaluate the safety and efficacy of various combination PAH therapies. A systematic search was conducted using the MEDLINE database (1966 and June 2012) for relevant clinical studies. Searches were limited to English, human and clinical trial using the terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, prostacyclin, prostaglandin, epoprostenol, treprostinil, iloprost, beraprost, endothelin receptor antagonist, bosentan, ambrisentan, sitaxsentan and pulmonary hypertension. Overall, 22 studies met inclusion criteria. Overall, the majority of trials demonstrated clinical efficacy in improving functional class, reducing pulmonary pressure, or increasing exercise capacity. Most trials were uncontrolled with small sample sizes investigating the acute effects of combination therapy and lacking long-term clinical outcomes. Adjunctive therapy was well tolerated by most patients. Overall, combination therapy is relatively safe and well tolerated. Published guidelines provide evidence-based recommendations for monotherapy. However, suggestions for combination therapy in refractory PAH patients are lacking. Several studies evaluating several combination therapies have been published. The preferred combination treatment among several PAH drug therapies remain controversial. Therefore, clinicians should consider ease of administration, cost, and tolerability when choosing specific combination therapies. Combination therapy appears promising for patients who are refractory to treatment or whose disease progression is not well controlled

  19. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance.

    Science.gov (United States)

    Rol, Nina; Timmer, Esther M; Faes, Theo J C; Vonk Noordegraaf, Anton; Grünberg, Katrien; Bogaard, Harm-Jan; Westerhof, Nico

    2017-03-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected and internal diameter decreases for vessels of different sizes is limited. Our aim was to quantify numbers of affected vessels and their internal diameter decrease for differently sized vessels in PAH in comparison with non-PAH patients. Internal and external diameters of transversally cut vessels were measured in five control subjects and six PAH patients. Resistance vessels were classified in Strahler orders, internal diameters 13 μm (order 1) to 500 μm (order 8). The number fraction, that is, percentage of affected vessels, and the internal diameter fraction, that is, percentage diameter of normal diameter, were calculated. In PAH, not all resistance vessels are affected. The number fraction is about 30%, that is, 70% of vessels have diameters not different from vessels of control subjects. Within each order, the decrease in diameter of affected vessels is variable with an averaged diameter fraction of 50-70%. Narrowing of resistance vessels is heterogeneous: not all vessels are narrowed, and the decrease in internal diameters, even within a single order, vary largely. This heterogeneous narrowing alone cannot explain the large resistance increase in PAH We suggest that rarefaction could be an important contributor to the hemodynamic changes. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

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    Martínez Anna

    2009-08-01

    Full Text Available Abstract Background Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs. Methods 19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS was evaluated by Real Time-PCR. Results Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p Conclusion In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.

  1. Anomalous left coronary artery from the pulmonary artery: intermediate results of coronary elongation.

    Science.gov (United States)

    Novick, William M; Li, Xiao F; Anic, Darko; Baskevitch, Alexander; Sandoval, Nestor; Gilbert, Christian L; Di Sessa, Thomas G

    2009-11-01

    A two coronary system is preferred for correcting anomalous left coronary artery from the pulmonary artery (ALCAPA); however, translocation is not always possible. In countries where neonatal arterial switch operations have not been perfected coronary transfer can be difficult. The purpose of this report is to describe the intermediate results using the coronary elongation and translocation technique in developing countries. Records of patients undergoing operation by the International Children's Heart Foundation team were reviewed (April 1993-October 2008) for those undergoing ALCAPA repair. All patients received a 2-D echocardiographic-color Doppler examination prior to discharge and at follow-up. A total of 13 patients were identified, age ranged from 9 days to 41 years. All but one patient were operated upon at one of our affiliate hospitals in Croatia, Belarus, China and Colombia. All patients presented with moderate to severe mitral regurgitation and cardiac failure. Follow-up ranged from six months to 9.5 years postoperatively. Color Doppler showed a patent left coronary artery; echocardiography estimated a normal left ventricular ejection fraction and improved mitral regurgitation in all patients. The technique provides an alternative approach to translocation for ALCAPA in countries where routine neonatal coronary transfer techniques may not be perfected. Intermediate results are comparable to translocation.

  2. Recombinant human interferon alpha 2b prevents and reverses experimental pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Pulmonary hypertension (PH is a progressive and fatal disease with no cure. Vascular remodeling in PH involves intraluminal growth of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Cell growth in these lesions is quasi-neoplastic, with evidence of monoclonality, apoptosis resistance and cancer-like metabolic derangements. Herein we tested the effect of human interferon alpha 2b (IFNα, a pleiotropic cytokine and anti-cancer therapeutic, on the development and progression of PH in the rat SU5416/hypoxia (SUH model and mouse hypoxia model of the disease. In both models IFNα attenuated the development of PH and reversed established PH as assessed by measuring right ventricular systolic pressure and right ventricular hypertrophy. The effect of IFNα was dependent on the type I interferon receptor (IFNAR since mice lacking a subunit of the IFNAR were not protected by IFNα. Morphometric analysis of pulmonary aterioles from hypoxic mice or SUH rats showed that IFNα inhibited pulmonary vascular remodeling in both models and that IFNα reversed remodeling in SUH rats with established disease. Immunohistochemical staining revealed that IFNα decreased the number of PCNA and Tunel positive cells in the wall of pulmonary arterioles. In vitro, IFNα inhibited proliferation of human pulmonary artery smooth muscle cells and as well as human pulmonary artery endothelial cell proliferation and apoptosis. Together these findings demonstrate that IFNα reverses established experimental PH and provide a rationale for further exploration of the use of IFNα and other immunotherpies in PH.

  3. Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

    Science.gov (United States)

    Wells, J. Michael; Farris, Roopan F.; Gosdin, Taylor A.; Dransfield, Mark T.; Wood, Michelle E.; Bell, Scott C.; Rowe, Steven M.

    2017-01-01

    Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:Apulmonary exacerbation risk in two well-characterized cohorts. PA:A may be a predictive marker in CF. PMID:27298019

  4. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment.

    Science.gov (United States)

    Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye

    2010-04-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.

  5. STARS knockout attenuates hypoxia-induced pulmonary arterial hypertension by suppressing pulmonary arterial smooth muscle cell proliferation.

    Science.gov (United States)

    Shi, Zhaoling; Wu, Huajie; Luo, Jianfeng; Sun, Xin

    2017-03-01

    STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein, which expressed early in cardiac development and involved in pathological remodeling. Abundant evidence indicated that STARS could regulate cell proliferation, but it's exact function remains unclear. In this study, we aimed to investigate the role of STARS in the proliferation of pulmonary arterial smooth muscle cells (PASMC) and the potential effect on the progression of pulmonary arterial hypertension (PAH). In this study, we established a PAH mouse model through chronic hypoxia exposure as reflected by the increased RVSP and RVHI. Western blot and RT-qPCR detected the increased STARS protein and mRNA levels in PAH mice. Next, we cultured the primary PASMC from PAH mice. After STARS overexpression in PASMC, STARS, SRF and Egr-1 were up-regulated significantly. The MTT assay revealed an increase in cell proliferation. Flow cytometry showed a marked inhibition of cell apoptosis. However, STARS silence in PASMC exerted opposite effects with STARS overexpression. SRF siRNA transfection blocked the effects of STARS overexpression in PASMC. In order to further confirm the role of STARS in PAH mice in vivo, we exposed STARS knockout mice to hypoxia and found lower RVSP and RVHI in knockout mice as compared with controls. Our results not only suggest that STARS plays a crucial role in the development of PAH by increasing the proliferation of PASMC through activation of the SRF/Egr-1 pathway, but also provides a new mechanism for hypoxia-induced PAH. In addition, STARS may represent a potential treatment target. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Non-arterial assessment of blood gas status in patients with chronic pulmonary disease.

    OpenAIRE

    Elborn, J. S.; Finch, M. B.; Stanford, C. F.

    1991-01-01

    Assessment of blood gas status is important in the management of patients with chronic pulmonary disease. Arterial puncture is often painful and may damage the arterial wall. Measurement of oxygen saturation by transcutaneous oximetry offers a non-invasive alternative to arterial methods but does not allow assessment of partial pressure of carbon dioxide. We have examined the value of oximetry and dorsal hand venous carbon dioxide as an alternative to arterial puncture. Transcutaneous oxygen ...

  7. Pulmonary Hypertension

    OpenAIRE

    Goetting, Michael; Schwarzer, Mario; Gerber, Alexander; Klingelhoefer, Doris; David A. Groneberg

    2017-01-01

    Pulmonary hypertension (PH) is characterized by the increase of the mean pulmonary arterial pressure in the lung circulation. Despite the large number of experimental and clinical studies conducted on pulmonary hypertension, there is no comprehensive work that analyzed the global research activity on PH so far. We retrieved the bibliometric data of the publications on pulmonary hypertension for two periods from the Web of science database. Here, we set the first investigation period from 1900...

  8. Hydroxysafflor yellow A (HSYA) attenuates hypoxic pulmonary arterial remodelling and reverses right ventricular hypertrophy in rats.

    Science.gov (United States)

    Li, Lei; Dong, Pengda; Hou, Congjia; Cao, Fangyuan; Sun, Shouli; He, Fa; Song, Yanping; Li, Sen; Bai, Yuhua; Zhu, Daling

    2016-06-20

    Carthamus tinctorius L. is a traditional herbal medicine native to China with properties of promoting blood circulation and removing blood stasis, which is used for the treatment of cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is the main constituent isolated from the flower of Carthamus tinctorius L. which is used as a marker substance in the quality control of Carthamus tinctorius L. in Chinese Pharmacopeia. This study is to investigate the hypertension attenuating effect of HSYA on hypoxia-induced pulmonary artery hypertension model rats, and the possible mechanism. The animal models were made by treating adult male Wistar rats (of the same age with the same weight of 200±25g) under hypoxia 24h per day for 9 days with or without administration of HSYA. The pulmonary arterial pressure of rats was measured after anesthetization; The right ventricular hypotrophy was evaluated by the right ventricular hypotrophy index (RVHI=[RV/(LV+S)]) as well as histomorphology assay with Hematoxylin and Eosin (HE) staining; The reducing of pulmonary artery remodelling was evaluated by histomorphology assay with HE staining; The proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by immunohistochemistry assays (PCNA and Ki67) and MTT assay. Cell cycle analysis and Weston-blot analysis were also performed in the study. HSYA reduced the mean right ventricular systolic pressure (RVSP) of rats with hypoxic pulmonary arterial hypertension (HPH) in a manner of concentration dependency. It significantly inhibited the PASMCs proliferation and attenuated the remodelling of the pulmonary artery and right ventricular hypertrophy. These findings suggested that HSYA protected against hypoxic induced pulmonary hypertension by reversing the remodelling of the pulmonary artery through inhibiting the proliferation and hypertrophy of PASMCs. This is in accordance with our previous finding that HSYA protects against the pulmonary artery

  9. Isolated unilateral absence of the right pulmonary artery in two cats visualized by computed tomography angiography

    Directory of Open Access Journals (Sweden)

    Tyler JM Jordan

    2016-10-01

    Full Text Available Case series summary Two cats were evaluated for progressive exercise intolerance, dyspnea and unilateral infiltrate of the left lung. Computed tomography angiography (CTA revealed absence of the right pulmonary artery in both cats with systemic arterial collateral vessels perfusing the right segmental pulmonary arteries. In one case, the collateral vessels arose from the esophageal artery, while in the other case they derived off the right costocervical trunk. One cat was diagnosed with pulmonary hypertension and was euthanized owing to progressive respiratory distress despite medical management with sildenafil, pimobendan, clopidogrel and furosemide. The other cat, without echocardiographic evidence of pulmonary hypertension, was successfully managed with furosemide and enalapril for more than 4 years. Relevance and novel information CTA allowed visualization of a rare congenital heart malformation, unilateral absence of the right pulmonary artery, in two cats and accurately characterized the source of collateral blood supply to the affected lung. Severe pulmonary hypertension may be a negative prognostic factor in cats with this condition as medical therapy in the cat without evidence of pulmonary hypertension resolved clinical signs, while the cat with severe pulmonary hypertension died from the disease.

  10. Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery

    Directory of Open Access Journals (Sweden)

    Marthan Roger

    2006-03-01

    Full Text Available Abstract Background Chronic alveolar hypoxia results in sustained arterial constriction, and increase in pulmonary vascular resistance leading to pulmonary artery hypertension (PAHT. The aim of this study was to investigate the effect of propofol and etomidate on pulmonary artery (PA reactivity in chronically hypoxic (CH rats, a model of pulmonary arterial hypertension (PAHT, in normoxic animals, and human PA. Methods CH rats were maintained 14 days at 380 mmHg pressure in a hypobaric chamber. Human tissue was retrieved from histological lung pieces from patients undergoing resection for carcinoma. Cumulative concentrations of anaesthetics were tested on isolated vascular rings precontracted with phenylephrine (PHE or 100 mM KCl. Statistical comparisons were done by ANOVA, followed, when needed, by Student t tests with Bonferroni correction as post-hoc tests. Results In normoxic rat PA, maximal relaxation (Rmax induced by etomidate and propofol was 101.3 ± 0.8% and 94.0 ± 2.3%, respectively, in KCl-precontracted rings, and 63.3 ± 9.7% and 46.1 ± 9.1%, respectively, in PHE-precontracted rings (n = 7. In KCl-precontracted human PA, Rmax was 84.7 ± 8.6 % and 66.5 ± 11.8%, for etomidate and propofol, respectively, and 154.2 ± 22.4 % and 51.6 ± 15.1 %, respectively, in PHE-precontracted human PA (n = 7. In CH rat PA, the relaxant effect of both anaesthetics was increased in PHE-precontracted and, for etomidate only, in KCl-precontracted PA. In aorta, CH induced no change in the relaxant effect of anaesthetics. Conclusion Propofol and etomidate have relaxant properties in PA from human and normoxic rat. The relaxant effect is specifically accentuated in PA from CH rat, mainly via an effect on the pharmacomechanical coupling. Etomidate appears to be more efficient than propofol at identical concentration, but, taking into account clinical concentrations, etomidate is less potent than propofol, which effect was in the range of clinical doses

  11. Isolated unilateral absence of a pulmonary artery: a case report and review of the literature

    NARCIS (Netherlands)

    A.D.J. ten Harkel (Arend); N.A. Blom (Nico); J. Ottenkamp (Jaap)

    2002-01-01

    textabstractOBJECTIVE: The purpose of the present study was to determine the symptomatology, diagnostic procedures, and therapeutic strategies of patients with an isolated unilateral absence of a pulmonary artery (UAPA). BACKGROUND: Isolated UAPA is a rare anomaly. Some case

  12. ECG-gated pulmonary artery CTA for evaluation of right ventricular function in patients with acute pulmonary embolism.

    Science.gov (United States)

    Liang, Hong-Wei; Zhao, De-Li; Liu, Xin-Ding; Chen, Peng; Zhou, Hai-Ting; Zhao, Cheng-Lei; Wang, Guo-Kun; Xu, Mei-Ling; Zhang, Jin-Ling

    2017-02-01

    To evaluate right ventricular function in patients with acute pulmonary embolism (APE) using electrocardiogram-gated CTA and to discuss the clinical value of pulmonary artery CTA PATIENTS AND METHODS: Based on death risk evaluation, 86 APE patients were divided into high-risk group (n=46) and non-high-risk group (n=40). The CT pulmonary embolism (PE) index and parameters of right ventricular function were analyzed from the CTPA images and compared between the two groups. Potential correlation between the two was also discussed. CT PE index (median 24.69%) of the high-risk group was obviously higher than that of the non-high-risk group (median 8.58%) (Pright ventricular function were significantly different between the two groups (Pright ventricular function. ECG-gated pulmonary artery CTA is suitable for assessing the severity of APE and right ventricular function. © 2016, Wiley Periodicals, Inc.

  13. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Antonio Lopes

    2014-01-01

    Full Text Available Congenital heart disease (CHD with intracardiac/extracardiac shunts is an important etiology of pulmonary arterial hypertension (PAH. The majority of children with congenital cardiac shunts do not develop advanced pulmonary vasculopathy, as surgical repair of the anomalies is now performed early in life. However, if not repaired early, some defects will inevitably lead to pulmonary vascular disease (truncus arteriosus, transposition of the great arteries associated with a ventricular septal defect (VSD, atrioventricular septal defects remarkably in Down syndrome, large, nonrestrictive VSDs, patent ductus arteriosus and related anomalies. The majority of patients are now assigned to surgery based on noninvasive evaluation only. PAH becomes a concern (requiring advanced diagnostic procedures in about 2-10% of them. In adults with CHD, the prevalence of advanced pulmonary vasculopathy (Eisenmenger syndrome is around 4-12%. [1] This article will discuss the diagnostic and management approach for PAH associated with CHD (PAH-CHD.

  14. Relationship of daily arterial blood pressure monitoring readings and arterial stiffness profile in male patients with chronic obstructive pulmonary disease combined with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Karoli N.A.

    2013-06-01

    Full Text Available The aim of the study was to determine correlation between arterial blood pressure daily rhythm and daily profile of arterial stiffness in male patients with chronic obstructive pulmonary disease (COPD and arterial hypertension. Materials et methods: Prospective investigation comprised 45 male patients with COPD and arterial hypertension. Individuals of 40 years younger and 80 years elder, patients with diabetes, stroke, angina pectoris, or heart infarction, vascular diseases, and exacerbation of chronic disease, bronchial and pulmonary diseases of other etiology were excluded from the analyses. Comparison group included 47 patients with essential arterial hypertension and without chronic respiratory diseases closely similar on general parameters with patients from main clinical series. Twenty-four-hour arterial blood pressure monitoring (ABPM and daily arterial stiffness monitoring were performed using BPLab® MnSDP-2 apparatus (Petr Telegin, Russian Federation. Results: Patients with COPD combined with arterial hypertension with raised arterial stiffness measures prevail over individuals in essential hypertension group. There is pathological alteration of the ABPM circadian rhythm and raised «Pressure load» values in raised arterial stiffness group. Conclusion: We found ABPM raised parameters in patients with COPD and arterial hypertension. It confirms necessity of ABPM in daily arterial stiffness assessment in patients with COPD.

  15. [The relationship between pulmonary arterial and small airway inflammation in smokers with and without chronic obstructive pulmonary disease].

    Science.gov (United States)

    Lao, Qifang; Zeng, Xiaoliang; Zhong, Xiaoning; Zhang, Jianquan; He, Zhiyi

    2014-12-01

    To investigate the relationship between pulmonary arterial and small airway inflammation in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13) and group C (smokers with stable COPD, n = 10). Normal pulmonary tissue was obtained more than 5 cm away from cancer lesion. The pathomorphological changes of the pulmonary muscularized arteries (MA) and small airways were observed by HE and Victoria blue-Van Gieson's stains.Lymphocytes infiltrated in the MA and small airways were observed by immunohistochemical methods. The characteristics and the correlations between pulmonary arterial inflammation and small airway inflammation were analyzed. The thickness of MA wall in the three groups was (119 ± 11), (139 ± 25) and (172 ± 28) µm respectively. The total small airway pathology score was (49 ± 10), (101 ± 34) and (163 ± 36) respectively. The score in group B and C was significantly higher than that in group A (P 0.05). The infiltration of CD(+)(3)T-lymphocytes and CD(+)(8)T-lymphocytes in the whole layer of MA was positively correlated with the total small airway pathology score respectively (r = 0.431,0.633, P arteries and small airways is the same kind of inflammation, mainly in the adventitia of pulmonary arteries and small airways. They are a part of pulmonary inflammation in COPD and promote the development of COPD.

  16. Anomalous Origin of One Pulmonary Artery From the Ascending Aorta: From Diagnosis to Treatment in Angola.

    Science.gov (United States)

    Manuel, Valdano; Sousa-Uva, Miguel; Morais, Humberto; Magalhães, Manuel P; Pedro, Albino; Miguel, Gade; Nunes, Maria A S; Gamboa, Sebastiana; Júnior, António P F

    2015-10-01

    Anomalous origin of one pulmonary artery is a rare congenital heart disease in which one pulmonary artery branch originates from the ascending aorta. To describe the experience of a cardiothoracic center in an African country to repair anomalous origin of one pulmonary artery in the context of Portugal-Angola collaboration. Between March 2011 and March 2015, four consecutive patients with anomalous origin of pulmonary artery branch underwent surgical correction. The mean age was 1.6 months. The mean weight was 4 kg. All had right pulmonary artery branch originating from the ascending aorta. All patients underwent direct implantation of right pulmonary branch to main pulmonary artery. Two patents had patent ductus arteriosus and one had atrial septal defect. Two patients had pulmonary hypertension. There was no registration of death. The mean cardiopulmonary bypass time was 75.5 ± 4.5 minutes, mean aortic cross-clamping time was 40 ± 5.6 minutes, and mean duration of the postoperative intensive care unit stay was 6.8 ± 5.7 days. At discharge, one patient had residual gradient of 25 mm Hg, the remainder had no significant gradient. The mean follow-up time was 11 months (5-28 months). One week after discharge, one patient presented operative wound dehiscence. At the last follow-up, all patients were alive, and no significant residual gradient or stenosis at site of anastomosis was observed. No reintervention was required. Anomalous origin of one pulmonary artery is a rare but potentially treatable lesion if operated early in life. Direct implantation was a good technique with good short-term results. © The Author(s) 2015.

  17. Transition from parenteral to oral treprostinil in pulmonary arterial hypertension.

    Science.gov (United States)

    Chakinala, Murali M; Feldman, Jeremy P; Rischard, Franz; Mathier, Michael; Broderick, Meredith; Leedom, Nicole; Laliberte, Kevin; White, R James

    2017-02-01

    Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. At Week 24, subjects were taking a median total daily dose of 44 (15 to 75) mg, with 25 of 31 using a 3-times-daily regimen at 7- to 9-hour intervals. The 6-minute walk distance was preserved (median +17 m [-98 to 95 m]) at its baseline of 446 m. Hemodynamic variables, including pulmonary vascular resistance, were similar at Week 24 except for mixed venous saturation, which dropped from a median of 71% to 68% (p < 0.001). Overall quality of life and treatment satisfaction measures did not change; however, mood-related symptom and treatment convenience subscores improved. Common adverse effects included headache, nausea, flushing and diarrhea. Lower risk patients managed on parenteral treprostinil may be candidates for transition to a more convenient, oral form of the drug. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Transcatheter closure of large right pulmonary artery-to-left atrial fistula

    Directory of Open Access Journals (Sweden)

    Karunakar Vadlamudi

    2013-01-01

    Full Text Available We report the successful transcatheter closure of right pulmonary artery fistula to left atrium in a six-year-old boy, who had presented with cyanosis and shortness of breath. The two-dimensional echocardiogram with bubble contrast study demonstrated the communication between right pulmonary artery and left atrium. Computerized tomography confirmed the diagnosis and delineated the anatomy. The fistula was closed successfully by a transcatheter trans-septal approach using an 18/20 duct occluder.

  19. Time dependent modifications in arterial flow in a transplanted pulmonary lobe.

    Science.gov (United States)

    Pillard, D; Cathignol, D; Fourcade, C; Tiano, R; Gadot, P; Regairaz, C; Vuillard, P; Descotes, J

    1977-01-01

    Study of pulmonary arterial flow in the transplanted lung by means of an implanted ultrasonic flowmeter enables us: 1. To confirm results obtained by other methods (De Bono,8 Strider14 and Strandberg18): without specific treatment, rejection of graft causes increased peripheral resistances and the pulmonary arterial flow decreases progressively. 2. To prove by direct observation the existence in the treated animal of authentic precapillary shunts whose importance can cause the animal's death through functional disorder alone.

  20. Pulmonary artery dissection in a patient with Eisenmenger syndrome treated with heart and lung transplantation

    DEFF Research Database (Denmark)

    Tønder, Niels; Køber, Lars; Hassager, Christian

    2004-01-01

    We report the case of a patient with known Eisenmenger syndrome due to congenital ventricular septal defect, who developed pulmonary artery dissection. The patient was successfully treated with heart and lung transplantation.......We report the case of a patient with known Eisenmenger syndrome due to congenital ventricular septal defect, who developed pulmonary artery dissection. The patient was successfully treated with heart and lung transplantation....

  1. Percutaneous transhepatic venous embolization of pulmonary artery aneurysm in Hughes-Stovin syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Ah; Kim, Man Deuk; Oh, Do Yun; Park, Pil Won [Bundang CHA General Hospital, Pochon CHA University, Seongnam (Korea, Republic of)

    2007-08-15

    Hughes-Stovin syndrome is an extremely rare entity. We present a case of a 42-year-old man, who developed deep vein and inferior vena cava (IVC) thrombosis, repeated internal bleeding and pulmonary artery aneurysms (PAAs). The patient presented with massive hemoptysis and with PAAs of a 2.5 cm maximum diameter. We describe the successful percutaneous transhepatic venous embolization of the PAAs due to occluded common vascular pathways to the pulmonary artery.

  2. A unique case of pulmonary artery catheter bleeding from the oximetry connection port

    Directory of Open Access Journals (Sweden)

    Suman Rajagopalan

    2014-12-01

    Full Text Available Pulmonary artery catheter is an invasive monitor usually placed in high-risk cardiac surgical patients to optimize the cardiac functions. We present this case of blood oozing from the oximetry connection port of the pulmonary artery catheter that resulted in the inability to monitor continuous cardiac output requiring replacement of the catheter. The cause of this abnormal bleeding was later confirmed to be due to a manufacturing defect.

  3. CYSTIC MEDIONECROSIS OF PULMONARY ARTERIAL TRUNK AS A PROBABLE CAUSE OF THROMBOSIS OF ITS BRANCHES

    Directory of Open Access Journals (Sweden)

    S. А. Boldueva

    2017-01-01

    Full Text Available The article presents a rare clinical case of thrombosis of large and small branches of the pulmonary artery, the probable cause of which was the degeneration of the muscle fibers of the wall of the pulmonary artery trunk by type of the cystic medionecrosis, possibly having a viral etiology. The disease was associated with the tumor of the pancreas body, smoldering purulent pancreatitis complicated by the syndrome of disseminated intravascular coagulation.

  4. Rosiglitazone Attenuated Endothelin-1-Induced Vasoconstriction of Pulmonary Arteries in the Rat Model of Pulmonary Arterial Hypertension via Differential Regulation of ET-1 Receptors

    Directory of Open Access Journals (Sweden)

    Yahan Liu

    2014-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is a fatal disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular failure and death. Activation of the endothelin (ET-1 system has been demonstrated in plasma and lung tissue of PAH patients as well as in animal models of PAH. Recently, peroxisome proliferator-activated receptor γ (PPARγ agonists have been shown to ameliorate PAH. The present study aimed to investigate the mechanism for the antivasoconstrictive effects of rosiglitazone in response to ET-1 in PAH. Sprague-Dawley rats were exposed to chronic hypoxia (10% oxygen for 3 weeks. Pulmonary arteries from PAH rats showed an enhanced vasoconstriction in response to ET-1. Treatment with PPARγ agonist rosiglitazone (20 mg/kg per day with oral gavage for 3 days attenuated the vasocontractive effect of ET-1. The effect of rosiglitazone was lost in the presence of L-NAME, indicating a nitric oxide-dependent mechanism. Western blotting revealed that rosiglitazone increased ETBR but decreased ETAR level in pulmonary arteries from PAH rats. ETBR antagonist A192621 diminished the effect of rosiglitazone on ET-1-induced contraction. These results demonstrated that rosiglitazone attenuated ET-1-induced pulmonary vasoconstriction in PAH through differential regulation of the subtypes of ET-1 receptors and, thus, provided a new mechanism for the therapeutic use of PPARγ agonists in PAH.

  5. Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

    Directory of Open Access Journals (Sweden)

    Antunes Edson

    2008-05-01

    Full Text Available Abstract Background Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis. Male Wistar rats were divided into three groups: saline (SAL; tauracholate (TAU and phospholipase A2 (PLA2. Pancreatitis was induced by administration of TAU or PLA2 from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh, sodium nitroprusside (SNP and phenylephrine (PHE in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC50 and maximal responses (EMAX were determined. Blood samples were collected for biochemical analysis. Results In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold or PLA2 (about 6.9-fold compared to saline group without changes in the maximal responses. Neither pEC50 nor EMAX values for Ach were altered in pulmonary rings in any group. Similarly, the pEC50 and the EMAX values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively. No changes were seen in the EMAX for PHE. The nitrite/nitrate (NOx- levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA2 protocol, respectively. Conclusion Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NOx- levels as

  6. EVALUATION OF RIGHT VENTRICULAR DYSFUNCTION AND PULMONARY ARTERY HYPERTENSION SECONDARY TO COPD SEVERITY BY ELECTROCARDIOGRAM AND ECHOCARDIOGRAPHY

    OpenAIRE

    Bhupendra Kumar; Nikhilesh; Ashok; Ashwin

    2015-01-01

    Patient with COPD carry increased risk of morbidity and mortality due to pulmonary artery hypertension, corpulmonale, cardiac arrhythmias, congestive heart fa ilure and pulmonary embolism. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate the cardiac changes secondary to severe COPD. AIM : To evaluate right ventricular dysfunction and pulmonary artery hypertension secondary to COPD severity as per GOLD gui...

  7. A case of William's syndrome associated peripheral pulmonary arterial stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Kyung Hwa; Hwang, Mi Soo; Kim, Sun Yong; Chang, Jae Chun; Park, Bok Hwan [College of Medicine, Yeungam University, Daegu (Korea, Republic of)

    1988-06-15

    William's syndrome, in order to more completely delineate the total spectrum of the disorder, indicates that 'infantile hypercalcemia', 'peculiar facies' and 'supravalvular aortic stenosis.' In has other many vascular anomalies, such as peripheral pulmonary arterial stenosis, coronary arterial stenosis, celiac arterial stenosis, and renal aterial stenosis. Only 32% of the patients have evidence of supravalvular aortic stenosis. And it is very rare disease entity that has been reported rarely in Korea. Recently authors experienced a case that was questioned William's syndrome with peripheral pulmonary arterial stenosis, clinically and preliminary radiologically and this case was confirmed by operation. Here we report a case of William's syndrome with peripheral pulmonary arterial stenosis and reviewed literatures.

  8. Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

    Science.gov (United States)

    Schäfer, Michal; Barker, Alex J; Kheyfets, Vitaly; Stenmark, Kurt R; Crapo, James; Yeager, Michael E; Truong, Uyen; Buckner, J Kern; Fenster, Brett E; Hunter, Kendall S

    2017-12-20

    Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4-dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population. Patients with PH (n=35) and controls (n=10) underwent 4-dimensional flow magnetic resonance imaging study for computation of helicity and vorticity in the main pulmonary artery (MPA), the right pulmonary artery, and the RV outflow tract. Helicity and vorticity were correlated with standard RV volumetric and functional indexes along with MPA stiffness assessed by measuring relative area change. Patients with PH had a significantly decreased helicity in the MPA (8 versus 32 m/s2; Pflow hemodynamic character in patients with PH assessed via quantitative analysis is considerably different when compared with healthy and normotensive controls. A strong association between helicity in pulmonary arteries and ventricular-vascular coupling suggests a relationship between the mechanical and flow hemodynamic domains. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle.

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    William Hartman

    Full Text Available Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF, can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs.48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia.Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy.

  10. Peripheral arterial disease in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pecci, R; De La Fuente Aguado, J; Sanjurjo Rivo, A B; Sanchez Conde, P; Corbacho Abelaira, M

    2012-10-01

    Cardiovascular disease (CV) is the second leading cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Peripheral arterial disease (PAD) is associated with cardiovascular disease, and its risk factors are common to other atherosclerotic diseases. The objective is to determine the prevalence of PAD in a population of patients with COPD using the ankle / brachial index (ABI) and to investigate the relationship between PAD and lung disease severity. In a prospective cross-sectional study, 246 patients with COPD were recruited. Patients were enrolled consecutively according to their admission to Povisa hospital from September 1, 2008, until March 1, 2010, and were assessed by clinical history, spirometry and ABI. The COPD severity was graded by GOLD criteria in spirometry. Overall, 84 patients (36.8%) had abnormal ABI results and 59 (70.2%) were asymptomatic for PAD. COPD patients with PAD had a higher prevalence of moderate to severe COPD (61.9% vs. 41.7%, P=0.004), lower mean forced expiratory volume in 1 second (FEV1) values (46.7% ± 15 vs. 52.3±14%, P=0.001) and a higher prevalence of hypertension (69% vs. 54.3%, P=0.03) and previous cardiovascular disease (34.5% vs. 21.3%, P=0.03). There was a high prevalence of asymptomatic PAD in the COPD patients we examined. Abnormal ABI results were associated with a higher prevalence of cardiovascular risk factors and more severe lung disease. The diagnosis of peripheral arterial disease in COPD is important because this is an entity that limits the patient's physical activity and impairs their quality of life in addition to turn it into a high cardiovascular risk patient that requiring additional therapeutic measures.

  11. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

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    Yacoub Magdi H

    2006-01-01

    Full Text Available Abstract Background To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH. Methods Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. Results We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P Conclusion Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.

  12. [Pulsatile Fontan: transcatheter closure of patent pulmonary artery. Follow up mid-term].

    Science.gov (United States)

    Gamboa, Ricardo; Mollón, Francisco P; Ríos Méndez, Raúl E; Cayré, Raúl O; Cazzaniga, Mario; Arroyo, Graciela M; Gutiérrez, Diego F

    2008-01-01

    We report the percutaneous closure of the pulmonary artery with residual shunt in patients with Fontan type circuit. Patients aged 9 and 11 years, with SaO2 of 88 and 96%, respectively. One of them coursing with headaches and functional class II. Both patients with total cavopulmonary anastomosis and fenestrated extracardiac conduit and permeable pulmonary artery (pulsatile Fontan). An Amplatzer duct-occluder device was implanted in the pulmonary artery entering from the femoral vein. Follow-up by means of clinical examination, imaging, and catetherization was pursued. Case 1, patency fenestration, Qp/Qs: 0.7/1. Case 2, closed fenestration, Qp/Qs; 1.3/1. We obtained immediate occlusion with 6/4 and 8/6 devices, respectively; pressure recordings revealed modification of the arterial morphology to biphasic; pulmonary pressure dropped 2 mm Hg in the first patient, without alteration in the second case; no changes in SaO2 were registered. Time of fluoroscopy was 57 and 45 minutes, respectively. Follow-up was maintained for 2.8 and 2.3 years, respectively. In patient 1, headaches disappeared and the fenestration was occluded with an Amplatzer septal-occluder one year later, raising SaO2 to 96%; no complications occurred nor was recanalization of the pulmonary artery needed in either case. Percutaneous occlusion of patent pulmonary artery in patients with Fontan type circuit is a feasible and effective procedure, and avoids overload of the single ventricle.

  13. The Impact of Moderate-Altitude Staging on Pulmonary Arterial Hemodynamics after Ascent to High Altitude

    Science.gov (United States)

    2010-01-01

    parasternal and apical transducer positions. All data were stored digitally, and poststudy data analysis (EchoPac, Version 6.5, GE Healthcare, Wauwatosa, WI...step in hypoxic pulmonary vaso- constriction of rat pulmonary artery resistance vessels. Circulation. 96:3647–3654. Ghofrani H.A., Reichenberger F

  14. Modern approaches to diagnostics and treatment of patients with pulmonary arterial hypertension

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    Т. Г. Волкова

    2015-10-01

    Full Text Available Pulmonary arterial hypertension (PAH is a pathological condition complicating many diseases. PAH is characterized by a progressive increase in pulmonary vascular resistance (PVR leading to the development of right ventricular failure and premature death of patients. The article describes the modern clinical classification of pulmonary hypertension and diagnostic algorithms. Also considered are basic approaches to standard therapy, results and experience in using modern drugs: endothelin receptor antagonists, prostanoids, phosphodiesterase inhibitors, as well as surgical methods of treatment.

  15. Coronary to Bronchial Artery Fistula Causing Massive Hemoptysis in Patients with Longstanding Pulmonary Tuberculosis

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    Yoon, Ji Young; Jeon, Eui Yong; Lee, In Jae; Koh, Sung Hye [Hallym University College of Medicine, Anyang (Korea, Republic of)

    2012-01-15

    We report on three cases of longstanding pulmonary tuberculosis patients with coronary to bronchial artery fistula (CBF) who presented with recurrent massive hemoptysis. The first and second patients died because of decreased functional pulmonary volume plus massive hemoptysis and cannulation failure of CBF due to hypovolemic vasospasm, respectively. When recurrent hemoptysis occurs despite successful embolization treatment, CBF should be considered as a potential bleeding source. Moreover, a coronary angiography should be performed, especially in patients with longstanding cardiopulmonary disease such as pulmonary tuberculosis.

  16. Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia

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    Junjing Su

    2017-07-01

    Full Text Available Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT pulmonary angiography and ventilation/perfusion (V/Q scintigraphy, chronic thromboembolic pulmonary hypertension (CTEPH was initially considered the most plausible diagnosis. However, during an attempted pulmonary endarterectomy, loose fibrous tissues were observed in the mediastinum and cryosection of the right pulmonary artery showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot-derived dopamine agonists, which are known to cause cardiac valve fibrosis and less frequently, non-cardiac fibrotic changes. The underlying mechanism is attributed to their interactions with serotonin receptors. There is much evidence that serotonin, a potent vasoconstrictor and mitogen, is involved in the pathogenesis of pulmonary hypertension. In conclusion, as CT and V/Q scintigraphy findings can occasionally be deceptive, physicians should be particularly aware of differential diagnoses in patients without obvious history of venous thromboembolism that are suspected of having chronic thromboembolic pulmonary hypertension.

  17. Lung and heart-lung transplantation in pulmonary arterial hypertension

    Science.gov (United States)

    López-Meseguer, Manuel; Quezada, Carlos A.; Ramon, Maria A.; Lázaro, María; Dos, Laura; Lara, Antonio; López, Raquel; Blanco, Isabel; Escribano, Pilar

    2017-01-01

    Background Real use of lung (LT) and heart-lung (HLT) transplantation in pulmonary arterial hypertension (PAH) is unknown. The objectives were to describe the indication of these procedures on PAH treatment in a national cohort of PAH patients, and to analyze the potential improvement of its indication in severe patients. Methods Eligibility for LT/HLT was assessed for each deceased patient. Incident patients from REHAP diagnosed between January 2007 and March 2015 and considered eligible for LT/HLT were grouped as follows: those who finally underwent transplantation (LTP) and those who died (D-Non-LT). Findings Of 1391 patients included in REHAP, 36 (3%) were LTP and 375 (27%) died. Among those who died, 36 (3%) were D-Non-LT. LTP and D-Non-LT were equal in terms of age, gender, and clinical status. Ten percent of those who died were functional class I-II. Patients functional class IV were less likely to undergo LT (8.3% LTP vs. 30.6% D-Non-LT, p = 0.017). Patients with idiopathic and drug/toxin-associated PAH were more likely to undergo LT (44.4% LTP vs. 16.7% D-Non-LT, p = 0.011). Conclusions The present results show that the use of LT/HLT could double for this indication. Relevant mortality in early functional class reflects the difficulties in establishing the risk of death in PAH. PMID:29161284

  18. Pediatric Pulmonary Arterial Hypertension and Hyperthyroidism: A Potentially Fatal Combination

    Science.gov (United States)

    Trapp, Christine M.; Elder, Robert W.; Gerken, Adrienne T.; Sopher, Aviva B.; Lerner, Shulamit; Rosenzweig, Erika B.

    2012-01-01

    Context: Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death. Cases and Setting: We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline. Evidence Synthesis: Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and β-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation. Conclusions: Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism. PMID:22622024

  19. The role of combination therapy in managing pulmonary arterial hypertension

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    Hossein-Ardeschir Ghofrani

    2014-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a complex, progressive disease with several pathobiological mechanisms, including the endothelin, nitric oxide and prostacyclin pathways. Current treatments for PAH target one of these pathways and, in more severe cases or instances of disease worsening, may be combined with a view to target multiple pathways in parallel. Treatment combination is performed sequentially (as an intensification from initial monotherapy or upfront (use of two or more therapies in treatment-naı¨ve patients. Whilst combination therapy has been historically considered to be an option for the treatment of PAH, supporting evidence was typically limited to expert opinion, clinical experience and registry data. Data from randomised controlled trials on sequential combination therapy in particular has grown in recent years, resulting in a change in the level of recommendations in the latest update to the PAH treatment algorithm. However, short-term trials have shown inconsistent results, and have not been powered to assess morbidity/mortality outcomes. More recent data from long-term trials suggest a potential clinical benefit associated with sequential combination therapy. In this review we will introduce the concept of combination therapy, consider the latest evidence for both sequential and upfront combination therapy, and discuss additional considerations when initiating combination therapy in clinical practice.

  20. Assessment of daily life physical activities in pulmonary arterial hypertension.

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    Vincent Mainguy

    Full Text Available BACKGROUND: In pulmonary arterial hypertension (PAH, the six-minute walk test (6MWT is believed to be representative of patient's daily life physical activities (DL(PA. Whether DL(PA are decreased in PAH and whether the 6MWT is representative of patient's DL(PA remain unknown. METHODS: 15 patients with idiopathic PAH (IPAH and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities >3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DL(PA. RESULTS: The mean number of daily steps and the mean daily energy expenditure and duration of physical activities >3 METs were all reduced in PAH patients compared to their controls (all p<0.05. The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p<0.01 and r = 0.85, p<0.01, respectively. CONCLUSION: DL(PA are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL(PA in PAH.

  1. Challenges in the diagnosis and treatment of pulmonary arterial hypertension.

    LENUS (Irish Health Repository)

    2012-12-01

    Advances in the diagnosis and management of pulmonary arterial hypertension (PAH) have resulted in significant improvements in outcomes for patients with this devastating and progressive disease. However, because of the non-specific nature of its symptoms, and the low level of suspicion among clinicians, prompt and accurate diagnosis of PAH as a rare disease remains a challenge. This article explains some of the issues that need to be addressed when faced with a patient with suspected PAH and describes how noninvasive and invasive techniques can be used effectively to ensure an accurate diagnosis. The availability of PAH-specific therapy means that once diagnosed, patients have a much greater chance of survival than they would have had in the past. However, despite improved survival, mortality is still high and, therefore, there is still room for improvement. It is currently recommended that patients with an inadequate clinical response to treatment receive sequential combination therapy; however, supportive data are still scarce. Although there is no clear explanation, these findings may be explained by the design and end-points chosen in clinical trials, the changing population of PAH and a need to improve the management strategy in this disease. Indeed, there is a clear need for randomised controlled studies that investigate whether adopting individualised treatment strategies, including upfront combination therapy, could help to optimise long-term management of patients with PAH.

  2. Information Experiences and Needs in Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension

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    Bodil Ivarsson

    2014-01-01

    Full Text Available Background. Pulmonary arterial hypertension (PAH and chronic thromboembolic pulmonary hypertension (CTEPH are fatal, noncurable, but treatable diseases that strongly affect the patients. Objective. To describe patients’ experience of information relating to PAH or CTEPH. Methods. A qualitative method using content analysis was applied. Seventeen patients (thirteen women and four men aged 28–73 years from a regional PAH centre were individually interviewed. Results. Three categories that describe patients’ experiences of information emerged: handling of information, struggling with feelings that also affect others, and vulnerability associated with uncertainty. The patients would have welcomed more information to relatives from the healthcare professionals. Shortcomings on communicating a prognosis were experienced. The mediated information and knowledge gave the patients insight into physical or psychosocial problems. Mutual exchange of information between patients and healthcare professionals were marred by different experiences of attitudes, behaviour, and ownership. Conclusions. In the future, healthcare organizations must struggle to achieve a holistic healthcare by making it more person-centred, and they must also promote cooperation between PAH centres and local healthcare providers. It is essential to determine the most appropriate and valuable path of information and communication and, thereby, the most cost-effective management of PAH or CTEPH.

  3. Impairment of pulmonary vascular reserve and right ventricular systolic reserve in pulmonary arterial hypertension.

    Science.gov (United States)

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Arredondo, Christian; Bouteldja, Nadia; Messeguer, Manuel López; Roman, Antonio

    2014-04-24

    Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH. Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: ΔmPAP > 5 mm Hg and 2: ΔmPAP ≤ 5 mm Hg. Cardiovascular reserve was estimated as the change (delta, Δ) during DST compared with rest, including ΔmPAP with respect to ΔCO (ΔmPAP/ΔCO). All patients were prospectively followed up for 2 years. PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher ΔmPAP/ΔCO (p 0.05). Pulmonary vascular reserve and RV systolic reserve are significantly impaired in patients with PAH. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome.

  4. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension.

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    Nikki L Jernigan

    Full Text Available Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1 compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2 Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3 Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4 This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models

  5. Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection.

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    Zhu, Rong; Bi, Li-Qing; Wu, Su-Ling; Li, Lan; Kong, Hui; Xie, Wei-Ping; Wang, Hong; Meng, Zi-Li

    2015-08-01

    The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia-induced pulmonary arterial hypertension (PAH) rat model. Ninety-six Sprague-Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)-1β and IL-10. Immunohistochemical analysis for ED1(+) monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia-induced PAH rats. Iptakalim also prevented an increase in IL-1β and a decrease in IL-10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia-induced PAH rats. Furthermore, iptakalim enhanced PECAM-1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM-1 and eNOS, suggesting that iptakalim may represent a

  6. Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension.

    Science.gov (United States)

    Hadri, Lahouaria; Kratlian, Razmig G; Benard, Ludovic; Maron, Bradley A; Dorfmüller, Peter; Ladage, Dennis; Guignabert, Christophe; Ishikawa, Kiyotake; Aguero, Jaume; Ibanez, Borja; Turnbull, Irene C; Kohlbrenner, Erik; Liang, Lifan; Zsebo, Krisztina; Humbert, Marc; Hulot, Jean-Sébastien; Kawase, Yoshiaki; Hajjar, Roger J; Leopold, Jane A

    2013-07-30

    Pulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, vascular injury is associated with downregulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) and alterations in Ca(2+) homeostasis in vascular smooth muscle cells that stimulate proliferation. We, therefore, hypothesized that downregulation of SERCA2a is permissive for pulmonary vascular remodeling and the development of PAH. SERCA2a expression was decreased significantly in remodeled pulmonary arteries from patients with PAH and the rat monocrotaline model of PAH in comparison with controls. In human pulmonary artery smooth muscle cells in vitro, SERCA2a overexpression by gene transfer decreased proliferation and migration significantly by inhibiting NFAT/STAT3. Overexpresion of SERCA2a in human pulmonary artery endothelial cells in vitro increased endothelial nitric oxide synthase expression and activation. In monocrotaline rats with established PAH, gene transfer of SERCA2a via intratracheal delivery of aerosolized adeno-associated virus serotype 1 (AAV1) carrying the human SERCA2a gene (AAV1.SERCA2a) decreased pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and fibrosis in comparison with monocrotaline-PAH rats treated with a control AAV1 carrying β-galactosidase or saline. In a prevention protocol, aerosolized AAV1.SERCA2a delivered at the time of monocrotaline administration limited adverse hemodynamic profiles and indices of pulmonary and cardiac remodeling in comparison with rats administered AAV1 carrying β-galactosidase or saline. Downregulation of SERCA2a plays a critical role in modulating the vascular and right ventricular pathophenotype associated with PAH. Selective pulmonary SERCA2a gene transfer may offer benefit as a therapeutic intervention in PAH.

  7. Paradoxical emboli: demonstration using helical computed tomography of the pulmonary artery associated with abdominal computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Delalu, P.; Ferretti, G.R.; Bricault, I.; Ayanian, D.; Coulomb, M. [Service Central de Radiologie et Imagerie Medicale, CHU Grenoble (France)

    2000-02-01

    We report the case of a 60-year-old woman with a recent history of a cerebrovascular accident. Because of clinical suspicion of pulmonary embolism and negative Doppler ultrasound findings of the lower limbs, spiral computed tomography of the pulmonary artery was performed and demonstrated pulmonary emboli. We emphasize the role of computed tomography of the abdomen, performed 3 min after the thoracic acquisition, which showed an unsuspected thrombus within the abdominal aorta and the left renal artery with infarction of the left kidney. Paradoxical embolism was highly suspected on computed tomography data and confirmed by echocardiography which demonstrated a patent foramen ovale. (orig.)

  8. Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2005-09-01

    Full Text Available Abstract background Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. Case presentation We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. Conclusion This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

  9. [Regulatory role of calcium activated chloride channel in pulmonary vascular structural remodeling in rats with pulmonary arterial hypertension induced by high pulmonary blood flow].

    Science.gov (United States)

    Wang, K; Pang, Y S; Su, D Y; Ye, B B; Qin, S Y; Liu, D L; Han, Y L

    2016-09-01

    To explore the regulatory role of calcium activated chloride channel (CaCC) in vascular structural remodeling in pathogenesis of pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow. An abdominal aorta and inferior vena cava shunting operation was used to induce high pulmonary blood flow and establish a PAH rat model.Seventy-five SD rats were randomly divided into normal, sham, shunt, niflumic acid (NFA) 1(0.2 mg/(kg·d))and NFA 2 (0.4 mg/(kg·d)) groups. There were 15 rats in each group. Pulmonary artery pressure and vascular structural remodeling were measured, arteriole contraction ratio among these groups were compared using vascular tone analysis system, and the electrophysiology of pulmonary artery smooth muscle cell (PASMC) was recorded using patch clamp technology. Differences between multiple groups were compared through variance analysis and that between groups with q test. Compared with normal ((14.4±1.3 ) mmHg, 1 mmHg=0.133 kPa)and sham groups ((13.5±2.3 ) mmHg), mean pulmonary artery pressure in shunt group ((27.4±2.4 ) mmHg) increased significantly (Ppulmonary artery pressure in NFA 1 group ((21.2±2.0) mmHg) and NFA 2 group ((22.3±2.0) mmHg) decreased significantly (PPulmonary vascular structural remodeling including pulmonary artery stenosis presented in shunt group. Compared with normal ((114.3±1.2)%) and sham ((115.5±1.1)%) groups, arteriole contraction ratio to 10(-5) mol/L phenylephrine in shunt group ((132.6±1.4)%) increased significantly (Ppulmonary vascular structural remodeling alleviated in NFA 1 and NFA 2 groups. Arteriole contraction ratio in NFA 1 group ((126.4±1.3)%) and NFA 2 group ((124.6±1.0)%) decreased significantly compared with shunt group (Ppulmonary arterial hypertension induced by high pulmonary blood flow through regulating membrane potential. NFA attenuate pulmonary vascular structural remodeling and pulmonary pressure through decreasing CaCC current density of PASMC membrane.

  10. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    Science.gov (United States)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  11. Fatal pulmonary arterial hypertension in an infant girl with incontinentia pigmenti.

    Science.gov (United States)

    Yasuda, Kenji; Minami, Noriaki; Yoshikawa, Yoko; Taketani, Takeshi; Fukuda, Seiji; Yamaguchi, Seiji

    2016-05-01

    We report the case of an infant girl with incontinentia pigmenti (IP) complicated by fatal pulmonary arterial hypertension (PAH). She was diagnosed with IP, based on the presence of specific skin lesions, neonatal seizures, hypereosinophilia and a maternal family history of IP. At the age of 2 months, she was diagnosed with PAH on systolic heart murmur due to tricuspid valve regurgitation. Despite several treatments for PAH but not including epoprostenol, severe PAH persisted and she died of pulmonary hypertensive crisis at the age of 5 months. On postmortem histopathology the pulmonary artery had severe intimal thickening, with occlusion or stenosis of the vascular lumen of the small pulmonary arteries as well as partial plexiform lesions, all of which were compatible with PAH. Modulation of nuclear factor-κB signaling may be involved in the development of PAH in IP. © 2016 Japan Pediatric Society.

  12. Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA in an Old Adult

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    Maryam Esmaeilzadeh

    2011-09-01

    Full Text Available The anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA is a rare congenital cardiac malformation. It presents predominantly in infancy and its main presenting feature is myocardial ischemia or heart failure. Survival to adulthood is quite uncommon. If untreated, mortality from ALCAPA approaches 90% in infancy; early recognition and surgical correction are, therefore, essential. With early surgical correction, the prognosis is good. There are two types of ALCAPA syndrome: the infant type and the adult type, each of which has different manifestations and outcomes. Infants experience myocardial infarction and congestive heart failure, and approximately 90% die within the first year of life. A literature review regarding this anomaly in teenagers and adults show that only 25 cases have been diagnosed during life and 18 additional cases of ALCAPA in these age groups have been diagnosed post mortem. We present a rare case of a 60-year-old man, who referred to our center due to dyspnea on exertion from the previous year without any history of chest pain and diagnosed as ALCAPA. Given the absence of ischemia and the patient’s age, only medical therapy was recommended.

  13. Intra-arterial digital subtraction angiography of the pulmonary arteries using a flow-directed balloon catheter in the diagnosis of pulmonary embolism

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    Rooij, W.J.J. van; Heeten, G.J. den (St. Elisabethziekenhuis Tilburg, Dept. of Radiology (Netherlands))

    1992-04-01

    Selective intra-arterial digital subtraction angiography (IA-DSA) of the pulmonary vessels was performed in 70 patients suspected of acute pulmonary embolism. A flow-directed Swan-Ganz pulmonary angiography catheter was used. The spatial resolution of the equipment used was 3.3 lp/mm for DSA and 6.0 lp/mm for conventional pulmonary angiography (CPA). Image quality of the angiograms was assessed by determining the highest visible branching division of the main pulmonary artery. The mean visible branching division for IA-DSA was 4.71 (range 3-7). In 10 patients where IA-DSA and CPA were performed during the same procedure there was no difference in visualization of peripheral arteries (mean 4.70 visible or for both modalities). IA-DSA makes the procedure rapid, saves on films and contrast material and allows good visualization of areas where exposure is difficult. The spatial resolution of state-of-the-art equipment permits sufficient definition of subsegmental vessels. The use of the flow-directed balloon catheter makes the examination easy to perform and minimizes the risk of catheter induced cardiac arrhythmias. (orig.).

  14. Non-arterial assessment of blood gas status in patients with chronic pulmonary disease.

    Science.gov (United States)

    Elborn, J S; Finch, M B; Stanford, C F

    1991-10-01

    Assessment of blood gas status is important in the management of patients with chronic pulmonary disease. Arterial puncture is often painful and may damage the arterial wall. Measurement of oxygen saturation by transcutaneous oximetry offers a non-invasive alternative to arterial methods but does not allow assessment of partial pressure of carbon dioxide. We have examined the value of oximetry and dorsal hand venous carbon dioxide as an alternative to arterial puncture. Transcutaneous oxygen saturation correlated with arterial oxygen saturation (r = 0.76, p less than 0.001) with an error of 2.1% and dorsal hand venous carbon dioxide tension correlated with the arterial tension (r = 0.84, p less than 0.001) with an error of 8%. Changes in oximetric oxygen saturation and venous carbon dioxide tension following oxygen therapy reflected arterial values. Assessment of blood gas status using oximetry and dorsal hand venous carbon dioxide tension is a useful alternative to arterial puncture.

  15. Pulmonary Artery Dimensions as a Prognosticator of Transplant-Free Survival in Scleroderma Interstitial Lung Disease.

    Science.gov (United States)

    Gleason, James Benjamin; Patel, Krunal B; Hernandez, Felix; Hadeh, Anas; Highland, Kristin B; Rahaghi, Franck; Mehta, Jinesh P

    2017-08-01

    Systemic sclerosis is a chronic debilitating autoimmune disease characterized by endothelial dysfunction and multi-organ fibrosis. Interstitial lung disease, a common manifestation of SSc, is termed scleroderma-related interstitial lung disease (SSc-ILD) and along with pulmonary hypertension contributes to a majority of deaths in SSc. SSc-ILD patients frequently develop pulmonary hypertension, which prognosticates a poorer outcome. We investigated pulmonary artery dimensions as an outcome predictor in patients with SSc-ILD. A retrospective chart review abstracting data from SSc-ILD patients evaluated at a large tertiary care center was performed. HRCT imaging was reviewed and pulmonary artery (PA) and ascending aorta (Ao) diameters were measured for calculation of the PA:Ao ratio. Additionally, demographics, vital signs, spirometric parameters, comorbidities, and mean pulmonary artery pressures were collected when available. Outcome analysis with lung transplant or death events within 4 years based on pulmonary artery size as well as PA:Ao ratio was performed. 70 SSc-ILD patients were identified. Mean pulmonary artery diameter and PA:Ao ratio was 31.17 and 1.07 mm, respectively. Patients with a pulmonary artery diameter ≥32 mm had higher risk of lung transplantation or death (p < 0.001) within 4 years. Patients with a PA:Ao ratio ≥1.1 also had higher risk of lung transplantation or death (p < 0.001) within 4 years. Unadjusted outcomes analyses also identified PA:Ao ratio ≥1.1 as an independent outcome predictor (hazard ratio 3.30, p < 0.001). In SSc-ILD patients, a PA:Ao ratio ≥1.1 is associated with higher risk of lung transplant or death. These data suggest that PA:Ao dimension may be used for prognostication in SSc-ILD.

  16. Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Apitz, Christian; Zimmermann, Rainer; Kreuder, Joachim; Jux, Christian; Latus, Heiner; Pons-Kühnemann, Joern; Kock, Ines; Bride, Peter; Kreymborg, Karsten Grosse; Michel-Behnke, Ina; Schranz, Dietmar

    2012-07-10

    The purpose of our study was to assess pulmonary endothelial function by vasodilator response to acetylcholine (Ach) administered in segmental pulmonary arteries in children with idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that there was a relationship among pulmonary endothelial response to Ach, severity of the disease, and clinical outcome. IPAH may be associated with pulmonary endothelial dysfunction; however, data regarding the impact of endothelial dysfunction on severity and prognosis of this disease are limited. Forty-three children and adolescents (mean age: 10.4 ± 5.5 years) with IPAH were included in the study. Changes in pulmonary blood flow in response to Ach were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. Mean PFR of all patients was 1.58 ± 0.67. Mean follow-up after catheterization was 55.7 ± 41.9 months. Freedom from serious cardiovascular events (lung transplantation or death) was 83% after 2 years, 76% after 3 years, and 57% after 5 years. PFR was related significantly to World Health Organization functional class. Receiver-operating characteristic curves revealed a PFR of 1.4 as the best cutoff value. Kaplan-Meier analysis demonstrated that a PFR of pulmonary endothelial response to Ach and prognosis of children with IPAH. As an adjunct to the usual testing protocol, this method provides additional information for therapeutic guidance. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

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    Serra Walter

    2010-07-01

    Full Text Available Abstract Background Pulmonary arterial hypertension (PAH in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. Objectives The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO. Methods Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of 2. They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO, HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR derived from the acceleration time of the pulmonary outflow tract (ACTpo, and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE. Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test. The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant. Results Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP

  18. T-helper 17 cell polarization in pulmonary arterial hypertension.

    Science.gov (United States)

    Hautefort, Aurélie; Girerd, Barbara; Montani, David; Cohen-Kaminsky, Sylvia; Price, Laura; Lambrecht, Bart N; Humbert, Marc; Perros, Frédéric

    2015-06-01

    Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic cells (DCs) and T cells, key driver and effector cells, respectively, of the immune system, may allow the identification of immunopathologic approaches to PAH management. Using flow cytometry, we performed immunophenotyping of monocyte-derived DCs (MoDCs) and circulating lymphocytes from patients with idiopathic PAH and control subjects. With the same technique, we performed cytokine profiling of both populations following stimulation, coculture, or both. We tested the immunomodulatory effects of a glucocorticoid (dexamethasone [Dex]) on this immunophenotype and cytokine profile. Using an epigenetic approach, we confirmed the immune polarization in blood DNA of patients with PAH. The profile of membrane costimulatory molecules of PAH MoDCs was similar to that of control subjects. However, PAH MoDCs retained higher levels of the T-cell activating molecules CD86 and CD40 after Dex pretreatment than did control MoDCs. This was associated with an increased expression of IL-12p40 and a reduced migration toward chemokine (C-C motif) ligand 21. Moreover, both with and without Dex, PAH MoDCs induced a higher activation and proliferation of CD4+ T cells, associated with a reduced expression of IL-4 (T helper 2 response) and a higher expression of IL-17 (T helper 17 response). Purified PAH CD4+ T cells expressed a higher level of IL-17 after activation than did those of control subjects. Lastly, there was significant hypomethylation of the IL-17 promoter in the PAH blood DNA as compared with the control blood. We have highlighted T helper 17 cell immune polarization in patients with PAH, as has been previously demonstrated in other chronic inflammatory and autoimmune conditions.

  19. Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response

    Science.gov (United States)

    Keserü, Benjamin; Barbosa-Sicard, Eduardo; Popp, Rüdiger; Fisslthaler, Beate; Dietrich, Alexander; Gudermann, Thomas; Hammock, Bruce D.; Falck, John R.; Weissmann, Norbert; Busse, Rudi; Fleming, Ingrid

    2008-01-01

    Recent findings have indicated a role for cytochrome P-450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) in acute hypoxic pulmonary vasoconstriction (HPV). Given that the intracellular concentration of EETs is determined by the soluble epoxide hydrolase (sEH), we assessed the influence of the sEH and 11,12-EET on pulmonary artery pressure and HPV in the isolated mouse lung. In lungs from wild-type mice, HPV was significantly increased by sEH inhibition, an effect abolished by pretreatment with CYP epoxygenase inhibitors and the EET antagonist 14,15-EEZE. HPV and EET production were greater in lungs from sEH−/− mice than from wild-type mice and sEH inhibition had no further effect on HPV, while MSPPOH and 14,15-EEZE decreased the response. 11,12-EET increased pulmonary artery pressure in a concentration-dependent manner and enhanced HPV via a Rho-dependent mechanism. Both 11,12-EET and hypoxia elicited the membrane translocation of a transient receptor potential (TRP) C6-V5 fusion protein, the latter effect was sensitive to 14,15-EEZE. Moreover, while acute hypoxia and 11,12-EET increased pulmonary pressure in lungs from TRPC6+/− mice, lungs from TRPC6−/− mice did not respond to either stimuli. These data demonstrate that CYP-derived EETs are involved in HPV and that EET-induced pulmonary contraction under normoxic and hypoxic conditions involves a TRPC6-dependent pathway.—Keserü, B., Barbosa-Sicard, E., Popp, R., Fisslthaler, B., Dietrich, A., Gudermann, T., Hammock, B. D., Falck, J. R., Weissmann, N., Busse, R., Fleming, I. Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response. PMID:18725458

  20. Effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease complicated by pulmonary arterial hypertension.

    Science.gov (United States)

    Wang, Peidong; Yang, Jie; Yang, Yanwei; Ding, Zhixin

    2017-01-01

    To evaluate the effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease (COPD) complicated by pulmonary arterial hypertension. Eighty-six patients who developed COPD and pulmonary arterial hypertension and received treatment from August 2013 to October 2014 were selected and randomly divided into an observation group and a control group using random number table, 43 in each group. Patients in the control group were orally administrated 20 mg of simvastatin, once a day. Patients in the observation group took 0.25g of azithromycin enteric-coated tablets, once a day, besides simvastatin. The treatment course of both groups was six months. Blood gas analysis indexes, forced expiratory volume in first second (FEV 1 ), six minutes walking distance, dyspnea grade and blood lipid parameter were recorded and compared between the two groups. Arterial partial pressure of oxygen (PaO 2 ) and arterial partial pressure of carbon dioxide (PaCO 2 ) of the observation group were (68.13±3.03) mmHg and (45.08±2.27) mmHg after treatment, respectively. In the control group, the values were (60.01±4.72) mmHg and (38.93±1.61) mmHg, respectively. The improvement amplitude of the observation group was superior to that of the control group ( P peripheral systolic blood pressure (PSBP) and peripheral diastolic blood pressure (PDBP) of patients in the observation group were both lower than those of the control group, and the difference had statistical significance ( P arterial hypertension as it can significantly relieve ventilation disturbance, improve lung function, and decrease pulmonary arterial pressure. Hence it is worth clinical promotion.

  1. NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Dumas, Sébastien J; Bru-Mercier, Gilles; Courboulin, Audrey; Quatredeniers, Marceau; Rücker-Martin, Catherine; Antigny, Fabrice; Nakhleh, Morad K; Ranchoux, Benoit; Gouadon, Elodie; Vinhas, Maria-Candida; Vocelle, Matthieu; Raymond, Nicolas; Dorfmüller, Peter; Fadel, Elie; Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2018-02-14

    Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown. Methods -We assessed the status of the glutamate-NMDAR axis in the pulmonary arteries of PAH patients and controls, through mass spectrometry imaging, western blotting and immunohistochemistry. We measured the glutamate release from cultured pulmonary vascular cells using enzymatic assays, and analyzed NMDAR regulation/phosphorylation through western blot experiments. The effect of NMDAR blockade on human pulmonary arterial smooth muscle cell (hPASMC) proliferation was determined using a BrdU incorporation assay. We assessed the role of NMDARs in vascular remodeling associated to pulmonary hypertension (PH), both in smooth muscle-specific NMDAR knockout mice exposed to chronic hypoxia and in the monocrotaline rat model of PH using NMDAR blockers. Results -We report glutamate accumulation, upregulation of the NMDAR, and NMDAR engagement reflected by increases in GluN1-subunit phosphorylation, in the pulmonary arteries of human PAH patients. K v channel inhibition and ETAR activation amplified calcium-dependent glutamate release from hPASMCs, and ETAR and PDGFR activation led to NMDAR engagement, highlighting crosstalk between the glutamate-NMDAR axis and major PAH-associated pathways. The PDGF-BB-induced proliferation of hPASMCs involved NMDAR activation and phosphorylated GluN1 subunit localization to cell-cell contacts, consistent with glutamatergic communication between

  2. Deformation pattern and predictive value of right ventricular longitudinal strain in children with pulmonary arterial hypertension.

    Science.gov (United States)

    Muntean, Iolanda; Benedek, Theodora; Melinte, Mihaela; Suteu, Carmen; Togãnel, Rodica

    2016-07-29

    Right ventricular function has been identified as an important prognostic factor in children with pulmonary arterial hypertension. The aim of the study was to assess the deformation pattern and prognostic value of right ventricular longitudinal strain in children with pulmonary arterial hypertension. We prospectively evaluated 46 children (25 with pulmonary arterial hyperetension and 21 age and sex matched controls) using conventional and speckle-tracking echocardiography, brain natriuretic peptide levels and clinical status expressed by WHO functional class and 6-min walking test. According to the clinical status after 12 months of follow-up, the pulmonary arterial hypertension patients were divided in two groups: non-worsening (13) and worsening (12). Right ventricular free wall longitudinal strain and strain rate were significantly lower in children with PAH compared with controls (-24.72 ± 3.48 vs -15.60 ± 3.40, p = 0.0001 and -1.44 ± 0.09 vs -1.09 ± 0.15, p = 0.0001, respectively). There was a more expressed decrease of basal than apical region of right ventricular free wall longitudinal strain/strain rate in pulmonary arterial hypertension patients compared with controls (strain: p = 0.0001 vs p = 0.07 and strain rate: p = 0.0001 vs p = 0.002). Comparing worsening and non-worsening pulmonary arterial hypertension patients there was a significant difference in Mid right ventricular free wall longitudinal strain (-14.00 ± 3.13 vs. -20.76 ± 4.62, p = 0.0001). In multivariable logistic regression analysis Mid right ventricular free wall longitudinal strain was an independent predictor of worsening in pulmonary arterial hypertension children (OR 0.45; 95 % CI: 0.21-0.96, p = 0.041). In ROC curve analysis a cut-off value of Mid right ventricular free wall longitudinal strain of -18.50 % predicted clinical worsening in pulmonary arterial hypertension children, with a sensitivity and specificity of 91

  3. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

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    Sakkas Lazaros

    2009-05-01

    Full Text Available Abstract Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH is well recognized. Vascular endothelial growth factor (VEGF has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP LCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.

  4. Is chronic obstructive pulmonary disease associated with increased arterial stiffness?

    DEFF Research Database (Denmark)

    Janner, Julie H; McAllister, David A; Godtfredsen, Nina S

    2012-01-01

    We hypothesize that airflow limitation is associated with increasing arterial stiffness and that having COPD increases a non-invasive measure of arterial stiffness - the aortic augmentation index (AIx) - independently of other CVD risk factors....

  5. Fibromuscular hyperplasia of the pulmonary artery in sudden infant and perinatal unexpected death.

    Science.gov (United States)

    Ottaviani, Giulia; Lavezzi, Anna Maria; Matturri, Luigi

    2009-01-01

    The purpose of this study was to describe cases presenting with fibromuscular hyperplasia of the pulmonary arteries that could belong to the group of sudden infant death syndrome (SIDS) and sudden unexpected perinatal death "gray zone" or borderline cases. In a total of 12 cases, eight females and four males, ranging in age from 39 gestational weeks to 93 postnatal days, dying suddenly and unexpectedly, a fibromuscular hyperplasia of the pulmonary artery was detected. Postmortem examinations were requested with a clinical SIDS or sudden unexpected perinatal death. A complete autopsy was performed, including close examination of the brainstem and cardiac conduction system. Histological examination showed the presence of various degrees of fibromuscular hyperplasia with fibrosis of the right (six cases), left (five cases) or both (one case) pulmonary arteries. In our cases, fibromuscular hyperplasia of the pulmonary artery alone might or might not have accounted for the sudden deaths, if it had not been for the concomitant presence of hypoplasia of the arcuate nucleus in the brainstem and/or cardiac conduction system abnormalities. Therefore, they were classified as SIDS/sudden unexpected perinatal death gray zone or borderline cases. Necropsy studies of sudden infant and perinatal death should always include an accurate gross and histological examination of the pulmonary arteries, as well as of the brainstem and cardiac conduction system.

  6. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Durand-Gasselin, Ingrid; Tcherakian, Colas; Le Pavec, Jérôme; Mazmanian, Michel; Fadel, Elie; Mussot, Sacha; Mercier, Olaf; Hervé, Philippe; Emilie, Dominique; Eddahibi, Saadia; Simonneau, Gérald; Souza, Rogério; Humbert, Marc

    2008-07-01

    Platelet-derived growth factor (PDGF) promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), and may play a role in the progression of pulmonary arterial hypertension (PAH), a condition characterized by proliferation of PASMCs resulting in the obstruction of small pulmonary arteries. To analyze the expression and pathogenic role of PDGF in idiopathic PAH. PDGF and PDGF receptor mRNA expression was studied by real-time reverse transcription-polymerase chain reaction performed on laser capture microdissected pulmonary arteries from patients undergoing lung transplantation for idiopathic PAH. Immunohistochemistry was used to localize PDGF, PDGF receptors, and phosphorylated PDGFR-beta. The effects of imatinib on PDGF-B-induced proliferation and chemotaxis were tested on human PASMCs. PDGF-A, PDGF-B, PDGFR-alpha, and PDGFR-beta mRNA expression was increased in small pulmonary arteries from patients displaying idiopathic PAH, as compared with control subjects. Western blot analysis revealed a significant increase in protein expression of PDGFR-beta in PAH lungs, as compared with control lungs. In small remodeled pulmonary arteries, PDGF-A and PDGF-B mainly localized to PASMCs and endothelial cells (perivascular inflammatory infiltrates, when present, showed intensive staining), PDGFR-alpha and PDGFR-beta mainly stained PASMCs and to a lesser extent endothelial cells. Proliferating pulmonary vascular lesions stained phosphorylated PDGFR-beta. PDGF-BB-induced proliferation and migration of PASMCs were inhibited by imatinib. This effect was not due to PASMC apoptosis. PDGF may play an important role in human PAH. Novel therapeutic strategies targeting the PDGF pathway should be tested in clinical trials.

  7. Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure

    Science.gov (United States)

    Pinciroli, Riccardo; Stowell, Christopher P.; Wang, Lin; Yu, Binglan; Fernandez, Bernadette O.; Feelisch, Martin; Mietto, Cristina; Hod, Eldad A.; Chipman, Daniel; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.; Zapol, Warren M.

    2014-01-01

    Rationale: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. Objectives: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure. Methods: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide. Measurements and Main Results: The age of volunteers was 41 ± 4 years (mean ± SEM), and their body mass index was 33.4 ± 1.3 kg/m2. Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 ± 2 to 23 ± 2 mm Hg; P transfusing 3-day blood (17 ± 2 to 18 ± 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 ± 2 to 12 ± 1 mm Hg; P Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502). PMID:25162920

  8. A novel mouse model of high flow-induced pulmonary hypertension-surgically induced by right pulmonary artery ligation.

    Science.gov (United States)

    Zhang, Anchen; Wang, Hongfei; Wang, Shengwei; Huang, Xiaofan; Ye, Ping; Du, Xinling; Xia, Jiahong

    2017-02-01

    This study sought to establish a new model of high-flow pulmonary hypertension (PH) in mice. This model may be useful for studies seeking to reduce the pulmonary vascular resistance and delay the development of PH caused by congenital heart disease. The right pulmonary artery was ligated via a right posterolateral thoracotomy. Pulmonary hemodynamics was evaluated by right heart catheterization immediately after ligation and at 2, 4, 8, and 12 wk postoperatively. The right ventricle (RV) and the left ventricle (LV) with septum (S) were weighed to calculate the RV/(LV + S) ratio as an index of right ventricular hypertrophy. Morphologic changes in the left lungs were analyzed, and percentages of muscularized pulmonary vessels were assessed by hematoxylin and eosin, elastica van Gieson and alpha-smooth muscle actin staining. All the study data were compared with data from a model of PH generated by hypoxic stimulation. A pulmonary hypertensive state was successfully induced by 2 wk after surgery. However, the morphologic analysis demonstrated that pulmonary vascular muscularization, as evaluated using right ventricular systolic pressure and RV/(LV + S), was not significantly increased until 4 wk postoperatively. When mice from the new model and the hypoxic model were compared, no significant differences were observed in any of the evaluated indices. High-flow PH can be induced within 4 wk after ligation of the right pulmonary artery, which is easily performed in mice. Such mice can be used as a model of high-flow PH. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. [Measurement of Rho-kinase in peripheral blood monocytes in patients with pulmonary arterial hypertension related to chronic obstructive pulmonary diseases].

    Science.gov (United States)

    Cai, Qian; Wu, Shangjie; Zhao, Xuefeng

    2012-05-01

    To determine effects of the RhoA/Rho kinase signaling pathway on patients with pulmonary arterial hypertension related to chronic obstructive pulmonary diseases by testing levels of Rho-associated coiled-coil containing protein kinase 1(ROCK1) in peripheral blood monocytes in healthy subjects, patients with chronic obstructive pulmonary diseases (COPD), and patients with pulmonary arterial hypertension related to COPD. Ten healthy subjects (Group A), 10 patients with COPD (Group B), and 10 patients with pulmonary arterial hypertension related to COPD (Group C) were enrolled, all of whom were hospitalized in the Third Hospital of Changsha between Dec. 2010 and Apr. 2011. Twenty milliliters of blood was collected from each subject. The peripheral blood mononuclear cells (PBMC) were separated by Percoll and, monocytes were incubated. Levels of ROCK1 in the three groups were measured by ELISA. The pulmonary function was measured by spirometric tests, and the pulmonary arterial systolic pressure (PASP) was detected by color Doppler echocardiogram. 1)The PASP in Group C was significantly higher than that of Groups A and B(P0.05). Rho kinase plays a key role in the pathogenesis of pulmonary arterial hypertension. The ROCK1 may be a marker of the severity of pulmonary arterial hypertension related to COPD.

  10. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves

    OpenAIRE

    Tian, Lian; Lammers, Steven R.; Kao, Philip H.; Reusser, Mark; Stenmark, Kurt R.; Hunter, Kendall S.; Qi, H. Jerry; Shandas, Robin

    2011-01-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, r...

  11. Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia

    DEFF Research Database (Denmark)

    Su, Junjing; Simonsen, Ulf; Carlsen, Jørn

    2017-01-01

    Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who...... showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot...... was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT) pulmonary angiography...

  12. Induced cytoskeletal changes in bovine pulmonary artery endothelial cells by resveratrol and the accompanying modified responses to arterial shear stress

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    Lerea Kenneth M

    2001-01-01

    Full Text Available Abstract Background Atherosclerosis and coronary heart disease (CHD are significant contributors to morbidity and mortality in developed countries. A noted exception is the low mortality of CHD in France, particularly the southwest region. This phenomenon, commonly referred to as the French paradox, may be associated with high consumption of red wine. We investigate whether the cardioprotective activity of red wine may involve the grape skin-derived polyphenol, resveratrol. We further test the possibility that resveratrol acts by modulating structural and functional changes in endothelial cells lining the blood vessel wall. Results Bovine pulmonary artery endothelial cells (BPAEC were incubated with resveratrol, with and without concurrent exposure to simulated arterial shear stress. Resveratrol significantly affected proliferation and shape of BPAEC; growth was suppressed and cells became elongated, based on morphologic analysis of rhodamine-conjugated phalloidin stained F-actin by confocal microscopy. Using selective signaling inhibitors, we showed that the resveratrol-induced cellular phenotype was dependent on intracellular calcium and tyrosine kinase activities, and assembly of actin microfilaments and microtubules, but was unrelated to PKC activity. Exposure to simulated arterial flow revealed that, whereas controls cells easily detached from the culture support in a time-dependent manner, resulting in total cell loss after a 5 min challenge with simulated arterial flow conditions, a significant percentage of the treated cells remained attached to the cultured plastic coverslips under identical experimental conditions, suggesting that they adhered more strongly to the surface. Western blot analysis shows that whereas cells treated with 25 μM and 100 μM resveratrol had no change in total ERK1/2, treatment did result in an increase in phosphorylated ERK1/2, which probably involved stabilization of the active enzyme. An increase in nitric

  13. Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Hood, Katie Y; Mair, Kirsty M; Harvey, Adam P; Montezano, Augusto C; Touyz, Rhian M; MacLean, Margaret R

    2017-07-01

    Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. HPASMCs from controls and PAH patients, and PASMCs from Nox1(-/-) mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1(-/-) mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Serotonin can induce cellular Src-related kinase-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT1B receptors contribute to

  14. Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure.

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    Han, June-Chiew; Guild, Sarah-Jane; Pham, Toan; Nisbet, Linley; Tran, Kenneth; Taberner, Andrew J; Loiselle, Denis S

    2017-01-01

    Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role. In this study, we tested this hypothesis by examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in rats treated with monocrotaline. Experiments were performed across multiple-scales: the whole-heart in vivo and ex vivo , and its trabeculae in vitro . Under the in vivo state where the RV was pressure-overloaded, we measured reduced systemic blood pressure and LV ventricular pressure. In contrast, under both ex vivo and in vitro conditions, where the effect of RV pressure overload was circumvented, we found that LV was capable of developing normal systolic pressure and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume remained lower, thereby contributing to lower LV mechanical work output. Concomitantly lower oxygen consumption and change of enthalpy were observed, and hence LV energy efficiency was unchanged. Our internally consistent findings between working-heart and trabecula experiments explain the rapid improvement of LV systolic function observed in patients with chronic pulmonary hypertension following surgical relief of RV pressure overload.

  15. Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

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    Jafri, Salema; Ormiston, Mark L

    2017-12-01

    Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4+ helper T cell populations, defined by excessive Th17 responses and impaired Treg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8+ T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

  16. Aberrant Chloride Intracellular Channel 4 Expression Contributes to Endothelial Dysfunction in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Wojciak-Stothard, Beata; Abdul-Salam, Vahitha B.; Lao, Ka Hou; Tsang, Hilda; Irwin, David C.; Lisk, Christina; Loomis, Zoe; Stenmark, Kurt R.; Edwards, John C; Yuspa, Stuart H.; Howard, Luke S.; Edwards, Robert J.; Rhodes, Christopher J.; Gibbs, J Simon R.; Wharton, John; Zhao, Lan; Wilkins, Martin R.

    2014-01-01

    Background Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodelled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension (PAH). CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of PAH. Methods and Results CLIC4 protein expression was increased in plasma and blood-derived endothelial cells from patients with idiopathic PAH (IPAH) and in the pulmonary vascular endothelium of 3 rat models of pulmonary hypertension. CLIC4 gene deletion markedly attenuated the development of chronic hypoxia-induced pulmonary hypertension in mice. Adenoviral overexpression of CLIC4 in cultured human pulmonary artery endothelial cells compromised pulmonary endothelial barrier function and enhanced their survival and angiogenic capacity, while CLIC4 shRNA had an inhibitory effect. Similarly, inhibition of CLIC4 expression in blood-derived endothelial cells from patients with IPAH attenuated the abnormal angiogenic behaviour that characterises these cells. The mechanism of CLIC4 effects involves p65-mediated activation of nuclear factor-κB, followed by stabilisation of hypoxia-inducible factor-1α and increased downstream production of vascular endothelial growth factor and endothelin-1. Conclusions Increased CLIC4 expression is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension. PMID:24503951

  17. Adaptive model based pulmonary artery segmentation in 3D chest CT

    Science.gov (United States)

    Feuerstein, Marco; Kitasaka, Takayuki; Mori, Kensaku

    2010-03-01

    The extraction and analysis of the pulmonary artery in computed tomography (CT) of the chest can be an important, but time-consuming step for the diagnosis and treatment of lung disease, in particular in non-contrast data, where the pulmonary artery has low contrast and frequently merges with adjacent tissue of similar intensity. We here present a new method for the automatic segmentation of the pulmonary artery based on an adaptive model, Hough and Euclidean distance transforms, and spline fitting, which works equally well on non-contrast and contrast enhanced data. An evaluation on 40 patient data sets and a comparison to manual segmentations in terms of Jaccard index, sensitivity, specificity, and minimum mean distance shows its overall robustness.

  18. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    Science.gov (United States)

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study. © 2015 Wiley Periodicals, Inc.

  19. Congenital anomalous/aberrant systemic artery to pulmonary venous fistula: Closure with vascular plugs & coil embolization

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    Pankaj Jariwala

    2014-01-01

    Full Text Available A 7-month-old girl with failure to thrive, who, on clinical and diagnostic evaluation [echocardiography & CT angiography] to rule out congenital heart disease, revealed a rare vascular anomaly called systemic artery to pulmonary venous fistula. In our case, there was dual abnormal supply to the entire left lung as1 anomalous supply by normal systemic artery [internal mammary artery]2 and an aberrant feeder vessel from the abdominal aorta. Left Lung had normal bronchial connections and normal pulmonary vasculature. The fistula drained through the pulmonary veins to the left atrium leading to ‘left–left shunt’. Percutaneous intervention in two stages was performed using Amplatzer vascular plugs and coil embolization to close them successfully. The patient gained significant weight in follow up with other normal developmental and mental milestones.

  20. Review of the diagnosis and pharmacological management of pulmonary arterial hypertension in connective tissue disease

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    Tang Chun-Pong

    2016-08-01

    Full Text Available Connective-tissue-disease-associated pulmonary arterial hypertension (CTD-PAH is a well-recognised pulmonary complication most commonly seen in patients with systemic sclerosis, followed by systemic lupus erythematosus and mixed connective tissue disease. In systemic-sclerosis-associated-pulmonary arterial hypertension (SSc-PAH, patients usually present late and the progression can be rapid with poor prognosis and survival. Early detection and prompt intervention of SSc-PAH is an important cornerstone to halt the disease progression. Various pulmonary vasodilatory agents were developed over the past two decades. They were shown to improve patients’ symptoms, functional status, exercise capacity, haemodynamics and long-term survival. Other immunosuppressive therapies also demonstrated to improve symptoms and functional status in certain group of patients. This article is to review the diagnosis and pharmacological management of patient with CTD-PAH.

  1. The Surgical Outcome of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery

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    Tasneem Muzaffar

    2014-06-01

    Full Text Available Background:: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA is a rare congenital anomaly which represents one of the most common causes of myocardial ischemia and infarction in children. This anomaly, if left untreated, results in a very high mortality rate within the first year of life. Yet, immediate surgical correction can lead to excellent results.. Objectives:: The present study aimed to determine the surgical outcome of ALCAPA.. Methods:: This study was conducted on 53 patients with ALCAPA operated from January 2005 to December 2012. Surgical repair was carried out as soon as the diagnosis was made. Surgery was thus undertaken on an urgent basis (within 48 hours in the patients with congestive heart failure or critical clinical status and on a semi- elective basis (within a few days in the remaining children. Operations for all the patients were performed through a median sternotomy using established standard cardiopulmonary bypass technique. Grouped variables were compared using chi-square test with Yates’ correction. Besides, McNemar’s test was used to assess the relationship between preoperative ejection fraction and mitral incompetence. All the analyses were performed using the SPSS statistical software, version 11.5 (SPSS Inc., Chicago, IL.. Results:: The patients’ median age at presentation was 4 months. The mean preoperative ejection fraction was 36.5%. The results showed a significant relationship between age at presentation and impairment of ejection fraction (P < 0.001. At first, 23% of our patients presented with ejection fraction < 35%. However, 6 months after the operation, the ejection fraction improved to a mean of 53.07% (SD = 8.5 ranging from 38 - 66%. There were 5 postoperative hospital deaths with an overall mortality rate of 9.6%.. Conclusions:: Excellent results with desirable long-term outcomes can be achieved in the infants with ALCAPA using coronary artery implantation

  2. TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction.

    Science.gov (United States)

    Rogers, Natasha M; Sharifi-Sanjani, Maryam; Yao, Mingyi; Ghimire, Kedar; Bienes-Martinez, Raquel; Mutchler, Stephanie M; Knupp, Heather E; Baust, Jeffrey; Novelli, Enrico M; Ross, Mark; St Croix, Claudette; Kutten, Johannes C; Czajka, Caitlin A; Sembrat, John C; Rojas, Mauricio; Labrousse-Arias, David; Bachman, Timothy N; Vanderpool, Rebecca R; Zuckerbraun, Brian S; Champion, Hunter C; Mora, Ana L; Straub, Adam C; Bilonick, Richard A; Calzada, Maria J; Isenberg, Jeffrey S

    2017-01-01

    Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1-/- mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n = 23) and without (n = 16) PH. Compared with controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA. In control PAs, treatment with exogenous TSP1 inhibited vasodilation and potentiated vasoconstriction to ET-1. Treatment of diseased PAs from PH patients with a CD47 blocking antibody improved sensitivity to vasodilators. Hypoxic wild type (WT) mice developed PH and displayed upregulation of pulmonary TSP1, CD47, and ET-1/ETA concurrent with down regulation of the transcription factor cell homolog of the v-myc oncogene (cMyc). In contrast, PH was attenuated in hypoxic CD47-/- mice while pulmonary TSP1 and ET-1/ETA were unchanged and cMyc was overexpressed. In CD47-/- pulmonary endothelial cells cMyc was increased and ET-1 decreased. In CD47+/+ cells, forced induction of cMyc suppressed ET-1 transcript, whereas suppression of cMyc increased ET-1 signaling. Furthermore, disrupting TSP1-CD47 signaling in pulmonary smooth muscle cells abrogated ET-1-stimulated hypertrophy. Finally, a CD47 antibody given 2 weeks after monocrotaline challenge in rats upregulated pulmonary cMyc and improved aberrations in PH-associated cardiopulmonary parameters. In pre-clinical models of PH CD47 targets cMyc to increase ET-1 signaling. In clinical PH TSP1-CD47 is upregulated, and in both, contributes to pulmonary arterial vasculopathy and dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  3. [Huge Solitary Fibrous Tumor of Pleura Combined with Peripheral Pulmonary Artery Aneurysm: A Case Resport].

    Science.gov (United States)

    Cheng, Yuanda; Gao, Yang; Zhang, Weixing; Zhang, Chunfang

    2015-08-01

    Solitary fibrous tumor of pleura (SFTP) is uncommon, accounts for less than 5% of all pleural tumors. Pulmonary artery aneurysm (PAA) is also not common, 80% of which often occurs in the main pulmonary trunk and peripheral PAA is rare. SFTP combined with PAA in one patient has not been reported. This paper reports a case of SFTP combined with peripheral PAA, and SFTP maybe accelerate PAA formation.

  4. Plastic bronchitis: symptomatic improvement after pulmonary arterial stenting in four patients with Fontan circulation.

    Science.gov (United States)

    Tanase, Daniel; Ewert, Peter; Eicken, Andreas

    2015-01-01

    Plastic bronchitis is a severe complication after a Fontan procedure, with an estimated incidence around 1-2% and poor prognosis. We present the cases of four patients with plastic bronchitis after a total cavopulmonary connection with a stenosis of the left pulmonary artery that was stented successfully. In three of the four patients, symptoms improved after catheter intervention in combination with pulmonary vasodilator and inhalative treatment.

  5. [Giant pulmonary artery aneurysm: etiology and an exceptional 17 years natural course].

    Science.gov (United States)

    Anzouan-Kacou, J-B; Séka, R; N'guetta, R; Kramoh, E; Konin, C

    2015-04-01

    True pulmonary artery aneurysm (AAP) is rare and represent less than 1% of intra-thoracic aneurysms. We report a case of a AAP in a patient with a likely cor triatrium sinister, with an obstructive membrane responsible for pulmonary hypertension, explaining AAP. The long-term evolution of 17 years is made to an uncomplicated myocardial infarction. The patient died eight months later suddenly probably due to the rupture of the PAA. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

    NARCIS (Netherlands)

    Fowler, E.D.; Benoist, D.; Drinkhill, M.J.; Stones, R.; Helmes, M.H.B.; Wüst, R.C.I.; Stienen, G.J.M.; Steele, D.S.; White, E.

    2015-01-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

  7. Use of Remote Pulmonary Artery Pressure Monitoring (CardioMEMS System) in Total Artificial Heart to Assess Pulmonary Hemodynamics for Heart Transplantation.

    Science.gov (United States)

    Gohar, Salman; Taimeh, Ziad; Morgan, Jeff; Frazier, O H; Arabia, Francisco; Civitello, Andrew; Nair, Ajith

    2017-11-08

    The temporary total artificial heart (TAH-t) has been valuable as a bridge to transplantation in patients with biventricular failure. However, the challenges of accurately assessing pulmonary vascular resistance after TAH-t implantation can preclude these patients from heart transplantation, especially those with pre-existing pulmonary hypertension. The CardioMEMS Heart Failure System (St. Jude's Medical, Little Canada, MN) comprises a wireless pressure sensor that is implanted percutaneously in the pulmonary artery and transmits real-time measurements of pulmonary artery pressures. Systolic and diastolic pulmonary artery (PA) pressures measurements have been well correlated between the CardioMEMS PA Sensor and traditional Swan-Ganz catheter and between the CardioMEMS PA Sensor and standard echocardiography. Here, we report the use of the CardioMEMS device in a patient with severe pulmonary hypertension supported with a SynCardia TAH-t (Tucson, AZ) during assessment for candidacy for transplantation.

  8. Canadian Cardiovascular Society and Canadian Thoracic Society Position Statement on Pulmonary Arterial Hypertension

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    David Langleben

    2005-01-01

    Full Text Available The Canadian Cardiovascular Society and the Canadian Thoracic Society requested a position statement on pulmonary arterial hypertension from leading Canadian experts. The present document is intended to act as an update for the clinician, to provide a template for the initial evaluation of patients, to enable the understanding of current therapeutic paradigms based on approved indications for Canada, to highlight new therapies on the horizon, and to state the positions of the Canadian Cardiovascular Society and the Canadian Thoracic Society on resource management for pulmonary arterial hypertension in Canada.

  9. 'End-stage' heart failure therapy: potential lessons from congenital heart disease: from pulmonary artery banding and interatrial communication to parallel circulation.

    Science.gov (United States)

    Schranz, Dietmar; Akintuerk, Hakan; Voelkel, Norbert F

    2017-02-15

    The final therapy of 'end-stage heart failure' is orthotopic heart, lung or heart-lung transplantation. However, these options are not available for many patients worldwide. Therefore, novel therapeutical strategies are needed. Based on pathophysiological insights regarding (1) the long-term impact of an obstructive pulmonary outflow tract in neonates with congenitally corrected transposition of the great arteries, (2) the importance of a restrictive versus a non-restrictive atrial septum in neonates born with a borderline left ventricle and (3) the significance of both, a patent foramen ovale and/or open ductus arteriosus for survival of newborns with persistent pulmonary hypertension, the current review introduces some therapeutical strategies that may be applicable to selected patients with heart failure. These strategies include (1) reversible pulmonary artery banding in left ventricular-dilated cardiomyopathy with preserved right ventricular function, (2) the creation of restrictive interatrial communication to treat diastolic (systolic) heart failure, (3) atrioseptostomy or reverse Potts shunt in pulmonary arterial hypertension and (4) return to a fetal, parallel circulation by combining atrioseptostomy and reversed Potts shunt with or without placement of a bilateral pulmonary artery banding. While still being experimental, it is hoped that the procedures presented in the current overview will inspire future novel therapeutic strategies that may be applicable to selected patients with heart failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. RGD peptides induce relaxation of pulmonary arteries and airways via β3-integrins.

    Science.gov (United States)

    Welschoff, Julia; Matthey, Michaela; Wenzel, Daniela

    2014-05-01

    Novel relaxants of pulmonary arteries and airways are of special interest to obtain insights into pulmonary signaling pathways and to develop treatment strategies for lung diseases. Herein, we demonstrate that Arg-Gly-Asp (RGD) peptides induce a dose-dependent relaxation of pulmonary arteries and airways in mouse. The relaxing effect was specific because it was strongly reduced using the control peptides RGE or RAD (Ppeptide sequences containing RGD and its flanking amino acids found in fibronectin showed a similar effect even at a 10-fold lower concentration. The relevance of RGD-induced pulmonary vasorelaxation was demonstrated in isometric force measurements, lung slices, and the isolated perfused lung model under normoxia and hypoxia and in vivo. As cell surface receptor we identified β3- but not β1-integrin subunits. Moreover, vasorelaxation by RGD peptides was strongly diminished after removal of the endothelium in endothelial nitric oxide synthase-deficient (eNOS(-/-) mice; PRGD peptides are relaxants of pulmonary arteries and airways. These findings may help to establish novel therapeutic approaches for pulmonary hypertension and obstructive lung disease.

  11. Anomalous origin of the left coronary artery from the right pulmonary artery with intramural aortic trajectory. Clinicosurgical diagnostic implications

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    Edmar Atik

    1999-08-01

    Full Text Available OBJECTIVE: Anomalous origin of the left coronary artery from the right pulmonary artery (AOLCARPA, is a rare entity that is usually associated with other defects. Of the 20 cases of AOLCARPA reported in the literature, 14 (70% had associations. We describe four patients with AOLCARPA without associated defects, but with a peculiar intramural aortic trajectory. METHODS: Fifty-five patients with anomalous origin of the left coronary artery were operated upon at INCOR-FMUSP. Four of the patients had the anomalous origin from the right pulmonary artery (RPA without associated defects but with intramural aortic trajectory. Clinical and laboratory examinations were analyzed, as well as surgical findings. RESULTS: All patients had congestive heart failure (CHF and 3 also had angina pectoris. Two patients had a murmur of mitral regurgitation, signs of myocardial infarction on the ECG and cardiomegaly. The shortening fraction varied from 9% to 23%. The hemodynamic study confirmed the diagnosis of anomalous origin of the coronary artery, but the intramural trajectory and the origin from the RPA were established only at surgery. In 3 patients, the technique of side-to-side anastomosis was performed with a good outcome. One patient, who underwent end-to-side anastomosis, died 6 months after the surgery. CONCLUSION: Association with other defects usually occurs in the AOLCARPA, and the intramural aortic trajectory is difficult to clinically diagnose but easy to surgically correct.

  12. The Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA: a Case Series and Brief Review

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    Aliasghar Moeinipour

    2016-02-01

    Full Text Available Background Anomalous left coronary artery from the pulmonary artery (ALCAPA is a rare congenital cardiovascular defect that occurs in approximately 1/300 000 live births or 0.5% of children with congenital heart disease. There are two types of ALCAPA syndrome: the infant type and the adult type. The most infants experience myocardial infarction and congestive heart failure, and approximately 90% die within the first year of life; also, without early surgical intervention they have a dismal prognosis. Materials and Methods We report 3- year experiences from January 2013 to January 2016 of Imam Reza Hospital center (a tertiary referral hospital North East of Iran that consist of all patients with ALCAPA syndrome. Results The Takeuchi procedure, were successfully performed in five children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA. There was no death and significant mitral regurgitation postoperative (n=0 in this short study. All of patients (n=5 had evidence of improving ischemic myocardium status by increasing of ejection fraction and regional wall motion of left ventricular in follow up echocardiography. Conclusion The only cure treatment for ALCAPA syndrome is surgical intervention that needs to be performed immediately after diagnosis to prevent myocardial infarction and chronic heart failure. Today, establishing a system with two coronary arteries is the goal in definitive surgical repair. The Takeuchi procedure is a prefer method to establish a two-coronary repair for ALCAPA.

  13. Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

    Science.gov (United States)

    Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

    2005-06-07

    Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of

  14. Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

    Science.gov (United States)

    Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

    2007-01-01

    Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly

  15. Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Paulin Roxane

    2011-09-01

    Full Text Available Background Pulmonary arterial hypertension (PAH is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis and the upregulation of growth factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET-1 promoting PASMC proliferation. Krüppel-like factor 5 (KLF5, is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation, proliferation, migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the implication of KLF5 in pulmonary arterial hypertension (PAH remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis. Methods and results We showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5 promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers survivin expression hyperpolarizing mitochondria membrane potential decreasing PASMC ability to undergo apoptosis. Conclusion We demonstrated for the first time that KLF5 is activated in human PAH and implicated in the pro-proliferative and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our findings will open new avenues of investigation on the role of KLF5 in PAH and might lead to the

  16. The role of nuclear factor of activated T cells in pulmonary arterial hypertension.

    Science.gov (United States)

    Chen, Rui; Yan, Jinchuan; Liu, Peijing; Wang, Zhongqun; Wang, Cuiping; Zhong, Wei; Xu, Liangjie

    2017-03-19

    Nuclear factor of activated T cells (NFAT) was first identified as a transcription factor about 3 decades ago and was not well studied until the development of immunosuppressant. Numerous studies confirm that calcineurin/NFAT signaling is very important in the development of vasculature and cardiovascular system during embryogenesis and is involved in the development of vascular diseases such as hypertension, atherosclerosis and restenosis. Recent studies demonstrated that NFAT proteins also regulate immune response and vascular cells in the pulmonary microenvironment. In this review, we will discuss how different NFAT isoforms contribute to pulmonary vascular remodeling and potential new therapeutic targets for treating pulmonary arterial hypertension.

  17. Ruptured penetrating ulcer of the ascending aorta with pulmonary artery compression.

    Science.gov (United States)

    Okiwelu, Ngozichukwuka; Finn, Chris; Vanden Driesen, Rohan; Sanders, Lucas; Joshi, Pragnesh

    2016-03-01

    Pulmonary artery involvement has been reported in various degrees of complicated dissection of the ascending aorta. The prognosis remains poor without high-risk surgical intervention, but conservative management can be considered in high-risk cases. We report a case of nonoperative management of an octogenarian who presented with a contained rupture of his proximal ascending aorta, likely from a penetrating atherosclerotic ulcer. It was complicated by extrinsic compression of the pulmonary trunk and transient pulmonary hypertension without features of acute right heart failure. He remained alive at the one-year follow-up. © The Author(s) 2014.

  18. Is CT angiography of the pulmonary arteries indicated in patients with high clinical probability of pulmonary embolism?

    Science.gov (United States)

    Martínez Montesinos, L; Plasencia Martínez, J M; García Santos, J M

    2017-06-30

    When a diagnostic test confirms clinical suspicion, the indicated treatment can be administered. A problem arises when the diagnostic test does not confirm the initially suspected diagnosis; when the suspicion is grounded in clinically validated predictive rules and is high, the problem is even worse. This situation arises in up to 40% of patients with high suspicion for acute pulmonary embolism, raising the question of whether CT angiography of the pulmonary arteries should be done systematically. This paper reviews the literature about this issue and lays out the best evidence about the relevant recommendations for patients with high clinical suspicion of acute pulmonary embolism and negative findings on CT angiography. It also explains the probabilistic concepts derived from Bayes' theorem that can be useful for ascertaining the most appropriate approach in these patients. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Accidental Left Circumflex Artery to Right Lung Fistula in a Suspected Case of Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Saeed Alipourparsa

    2014-01-01

    Full Text Available A 56-year-old woman was referred to the cardiology department of the Shahid Modarres hospital. The patient had a history of pulmonary thromboembolism 20 years ago which had been managed by the inferior vena cava filter and since then the patient has been on warfarin. Her chief complaint was chronic dyspnea on exertion (NYHA class II from several years ago. Right and left heart catheterization was performed for evaluation of pulmonary artery pressure. We found rich collateral formations between LCX as well as RCA and right pulmonary artery, primarily assumed as multiple fistulas. Among patients who have chronic thromboembolic pulmonary hypertension, systemic collateral supply to the pulmonary parenchyma has been previously reported to occur from both bronchial and/or nonbronchial systemic circulations. Our patient had neither signs of heart failure nor myocardial ischemia and, thus, was a candidate for conservative management. The adenosine pulmonary reactivity test was not performed because of low pulmonary pressure which had been estimated to be high.

  20. MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction.

    Science.gov (United States)

    Dahan, Diana; Hien, Tran Thi; Tannenberg, Philip; Ekman, Mari; Rippe, Catarina; Boettger, Thomas; Braun, Thomas; Tran-Lundmark, Karin; Tran, Phan-Kiet; Swärd, Karl; Albinsson, Sebastian

    2017-01-01

    Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling. © 2017 S. Karger AG, Basel.

  1. Use of pulmonary artery catheter in coronary artery bypass graft. Costs and long-term outcomes.

    Directory of Open Access Journals (Sweden)

    Fei Xu

    Full Text Available Pulmonary artery catheters (PAC are used widely to monitor hemodynamics in patients undergoing coronary bypass graft (CABG surgery. However, recent studies have raised concerns regarding both the effectiveness and safety of PAC. Therefore, our aim was to determine the effects of the use of PAC on the short- and long-term health and economic outcomes of patients undergoing CABG.1361 Chinese patients who consecutively underwent isolated, primary CABG at the Cardiovascular Institute of Fuwai Hospital from June 1, 2012 to December 31, 2012 were included in this study. Of all the patients, 453 received PAC during operation (PAC group and 908 received no PAC therapy (control group. Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis and propensity score matched-pair analysis was used to yield two well-matched groups for further comparison.The patients who were managed with PAC more often received intraoperative vasoactive drugs dopamine (70.9% vs. 45.5%; P<0.001 and epinephrine (7.7% vs. 2.6%; P<0.001. In addition, costs for initial hospitalization were higher for PAC patients ($14,535 vs. $13,873, respectively, p = 0.004. PAC use was neither associated with the perioperative mortality or major complications, nor was it associated with long-term mortality and major adverse cardiac and cerebrovascular events. In addition, comparison between two well-matched groups showed no significant differences either in baseline characteristics or in short-term and long-term outcomes.There is no clear indication of any benefit or harm in managing CABG patients with PAC. However, use of PAC in CABG is more expensive. That is, PAC use increased costs without benefit and thus appears unjustified for routine use in CABG surgery.

  2. New concepts in the invasive and non invasive evaluation of remodelling of the right ventricle and pulmonary vasculature in pulmonary arterial hypertension.

    Science.gov (United States)

    Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio

    2009-03-12

    Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH.

  3. Genetic counselling for pulmonary arterial hypertension: a matter of variable variability

    NARCIS (Netherlands)

    Leter, E. M.; Boonstra, A. B.; Postma, F. B.; Gille, J. J. P.; Meijers-Heijboer, E. J.; Vonk Noordegraaf, A.

    2011-01-01

    We report three cases which highlight the complex considerations surrounding genetic counselling for pulmonary arterial hypertension (PAH). The first counselee developed PAH symptoms shortly after his daughter's death from PAH and was diagnosed with a delay of 1 year. An early diagnosis of familial

  4. Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Butrous Ghazwan S

    2011-10-01

    Full Text Available Abstract Background Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. Methods Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin, lipophobic (pravastatin and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. Results Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550 was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. Conclusions Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.

  5. Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre

    NARCIS (Netherlands)

    Douwes, Johannes M.; Roofthooft, Marcus T. R.; Van Loon, Rosa L. E.; Ploegstra, Mark-Jan; Bartelds, Beatrijs; Hillege, Hans L.; Berger, Rudolphus

    2014-01-01

    Objective In paediatric pulmonary arterial hypertension (PAH), the effectiveness of add-on combination PAH-therapy has not yet been systematically studied. The purpose of this study was to determine the effect of sildenafil add-on therapy in paediatric PAH patients treated with bosentan. Methods In

  6. Aneurysm of the Pulmonary Artery, a Systematic Review and Critical Analysis of Current Literature

    NARCIS (Netherlands)

    Duijnhouwer, A.L.; Navarese, E.P.; Dijk, A.P.J. van; Loeys, B.L.; Roos-Hesselink, J.W.; Boer, M.J. de

    2016-01-01

    BACKGROUND: Pulmonary artery (PA) aneurysms are rare and their related complications like dissection or rupture have been so far reported in a few reports, and a systematic description of the disease is lacking. To identify patients with PA aneurysm, at high-risk for complications, is critical. We

  7. Relationship between chronic obstructive pulmonary disease and subclinical coronary artery disease in long-term smokers

    DEFF Research Database (Denmark)

    Rasmussen, Thomas; Køber, Lars; Pedersen, Jesper Holst

    2013-01-01

    Cardiovascular conditions are reported to be the most frequent cause of death in patients with chronic obstructive pulmonary disease (COPD). However, it remains unsettled whether severity of COPD per se is associated with coronary artery disease (CAD) independent of traditional cardiovascular risk...

  8. Isolated unilateral absence of a pulmonary artery: a case report and review of the literature

    NARCIS (Netherlands)

    ten Harkel, A. Derk Jan; Blom, Nico A.; Ottenkamp, Jaap

    2002-01-01

    OBJECTIVE: The purpose of the present study was to determine the symptomatology, diagnostic procedures, and therapeutic strategies of patients with an isolated unilateral absence of a pulmonary artery (UAPA). BACKGROUND: Isolated UAPA is a rare anomaly. Some case reports exist, but the best

  9. Pulmonary arterial hypertension in congenital heart disease : An epidemiologic perspective from a Dutch registry

    NARCIS (Netherlands)

    Duffels, M. G. J.; Engelfriet, P. M.; Berger, R. M. F.; van Loon, R. L. E.; Hoendermis, E.; Vriend, J. W. J.; Bresser, P.; Mulder, B. J. M.; van der Velde, Enno T.

    2007-01-01

    Background: Pulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-topulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients

  10. Bleeding Pulmonary Artery Pseudoaneurysm Secondary to Squamous Cell Lung Cancer: Computed Tomography Findings and Endovascular Management

    Energy Technology Data Exchange (ETDEWEB)

    Akpinar, E.; Turkbey, B.; Canyigit, M.; Peynircioglu, B.; Hazirolan, T.; Pamuk, A.G.; Cil, B.E. [Hacettepe Univ. School of Medicine, Ankara (Turkey). Dept. of Radiology

    2006-11-15

    A case of bleeding pulmonary artery pseudoaneurysm secondary to squamous cell lung cancer is reported. The patient presented with massive hemoptysis, diagnosis was made with multidetector computed tomography, and the pseudoaneurysm was successfully embolized with platinum coils. Hemoptysis ceased following the procedure.

  11. Pulmonary artery thrombosis in a patient with right‑sided heart failure

    African Journals Online (AJOL)

    2013-09-19

    Sep 19, 2013 ... present a case of a 76-year-old man, known to have cardiac failure on regular treatment who presented with predominant features of right-sided heart failure accompanied with dizziness. He was diagnosed to have pulmonary artery thrombosis by computerized tomography. Anticoagulation therapy was ...

  12. Pulmonary artery thrombosis in a patient with right-sided heart failure

    African Journals Online (AJOL)

    We present a case of a 76-year-old man, known to have cardiac failure on regular treatment who presented with predominant features of right-sided heart failure accompanied with dizziness. He was diagnosed to have pulmonary artery thrombosis by computerized tomography. Anticoagulation therapy was initiated with ...

  13. Pulmonary artery location during microgravity activity: Potential impact for chest-mounted Doppler during space travel

    Science.gov (United States)

    Hadley, A. T., III; Conkin, J.; Waligora, J. M.; Horrigan, D. J., Jr.

    1984-01-01

    Doppler, or ultrasonic, monitoring for pain manifestations of decompression sickness (the bends) is accomplished by placing a sensor on the chest over the pulmonary artery and listening for bubbles. Difficulties have arisen because the technician notes that the pulmonary artery seems to move with subject movement in a one-g field and because the sensor output is influenced by only slight degrees of sensor movement. This study used two subjects and mapped the position of the pulmonary artery in one-g, microgravity, and two-g environments using ultrasound. The results showed that the pulmonary artery is fixed in location in microgravity and not affected by subject position change. The optimal position corresponded to where the Doppler signal is best heard with the subject in a supine position in a one-g environment. The impact of this result is that a proposed multiple sensor array on the chest proposed for microgravity use may not be necessary to monitor an astronaut during extravehicular activities. Instead, a single sensor of approximately 1 inch diameter and mounted in the position described above may suffice.

  14. Clinical classification in pediatric pulmonary arterial hypertension associated with congenital heart disease

    NARCIS (Netherlands)

    Zijlstra, Willemijn M. H.; Douwes, Johannes M.; Ploegstra, Mark-Jan; Krishnan, Usha; Roofthooft, Marcus T. R.; Hillege, Hans L.; Ivy, D. Dunbar; Rosenzweig, Erika B.; Berger, Rolf M. F.

    Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore

  15. Endovascular Treatment of an Aneurysmal Aberrant Systemic Artery Supplying a Pulmonary Sequestrum

    DEFF Research Database (Denmark)

    Kristensen, Katrine Lawaetz; Duus, Louise Aarup; Elle, Bo

    2015-01-01

    An aberrant systemic artery originating from the abdominal aorta supplying a pulmonary sequestration is a rare congenital malformation. This causes a left-to-left shunt. Symptoms include recurrent pneumonias, hemoptysis, and, in the long term, heart failure. Aneurysm of the aberrant vessel...

  16. Frequency and Prognostic Significance of Hemoptysis in Pediatric Pulmonary Arterial Hypertension

    NARCIS (Netherlands)

    Roofthooft, Marcus T. R.; Douwes, Johannes M.; Vrijlandt, Elianne J. L. E.; Berger, Rolf M. F.

    2013-01-01

    Data concerning the prevalence, risk factors, and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch national cohort of 74 children with either idiopathic or heritable PAH (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease

  17. The anomalous origin of the branch pulmonary artery from the ascending aorta.

    Science.gov (United States)

    Garg, Pankaj; Talwar, Sachin; Kothari, Shyam Sunder; Saxena, Anita; Juneja, Rajnish; Choudhary, Shiv Kumar; Airan, Balram

    2012-07-01

    The anomalous origin of one pulmonary artery branch from the aorta (AOPA) is rare. We report our single-institution surgical experience with this condition. Between January 1994 and February 2011, 17 patients (age: 1 month-25 years) with AOPA underwent surgery at our institute. Thirteen patients had an anomalous origin of the right pulmonary artery (RPA) while four had an anomalous origin of the left pulmonary artery (LPA) from the aorta. In patients with anomalous RPA, 11 patients had the proximal type and two patients had the distal type of AOPA. Four patients had associated Tetralogy of Fallot (TOF). In 14 patients, direct implantation into the main pulmonary artery was performed, while three patients required interpositon of a graft. There was one operative death due to persistent hypoxia in a 7-month old child with TOF and an anomalous LPA from the aorta. At a median follow-up of 36.5 months (range: 2-192 months), all 16 survivors were asymptomatic. On echocardiography, two patients showed a gradient of 25 and 30 mmHg across the anastomosis and are being followed up. In our experience, early repair of AOPA results in acceptable haemodynamic and anatomic results. Long-term survival can be expected with a low incidence of re-operation or re-intervention.

  18. Growth in children with pulmonary arterial hypertension : a longitudinal retrospective multiregistry study

    NARCIS (Netherlands)

    Ploegstra, Mark-Jan; Ivy, D. Dunbar; Wheeler, Jeremy G.; Brand, Monika; Beghetti, Maurice; Rosenzweig, Erika B.; Humpl, Tilman; Iriart, Xavier; Muros-Le Rouzic, Erwan; Bonnet, Damien; Berger, Rolf M. F.

    BACKGROUND: To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. METHODS: We did a retrospective longitudinal study of height and body-mass index in

  19. Effects of exercise training in patients with idiopathic pulmonary arterial hypertension

    NARCIS (Netherlands)

    de Man, F.S.; Handoko, M.L.; Groepenhoff, H.; van 't Hul, A.J.; Abbink, J.; Koppers, R.J.H.; Grotjohan, H.P.; Twisk, J.W.R.; Bogaard, H.J.; Boonstra, A.; Postmus, P.E.; Westerhof, N.; van der Laarse, W.J.; Vonk Noordegraaf, A.

    2009-01-01

    We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise

  20. Persistent pulmonary hypertension of the newborn with transposition of the great arteries

    NARCIS (Netherlands)

    Roofthooft, Marcus T. R.; Bergman, Klasina A.; Ebels, Tjark; Bartelds, Beatrijs; Berger, Rolf M. F.; Waterbolk, T

    Background. Persistent pulmonary hypertension of the newborn (PPHN) in patients with transposition of the great arteries (TGA) is reported to be a high-risk and often therapy-resistant condition, associated with a high mortality. However, data on its incidence and prognosis are scarce and originate

  1. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    Science.gov (United States)

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.

  2. Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification

    NARCIS (Netherlands)

    Riel, A.C. van; Schuuring, M.J.; Hessen, I.D. van; Zwinderman, A.H.; Cozijnsen, L.; Reichert, C.L.; Hoorntje, J.C.A.; Wagenaar, L.J.; Post, M.C.; Dijk, A.P.J. van; Hoendermis, E.S.; Mulder, B.J.; Bouma, B.J.

    2014-01-01

    BACKGROUND: The aging congenital heart disease (CHD) population is prone to develop a variety of sequelae, including pulmonary arterial hypertension (PAH). Previous prevalence estimates are limited in applicability due to the use of tertiary centers, or database encoding only. We aimed to

  3. Acute Vasodilator Response in Pediatric Pulmonary Arterial Hypertension : Current Clinical Practice From the TOPP Registry

    NARCIS (Netherlands)

    Douwes, Johannes M.; Humpl, Tilman; Bonnet, Damien; Beghetti, Maurice; Ivy, D. Dunbar; Berger, Rolf M. F.

    2016-01-01

    BACKGROUND In pulmonary arterial hypertension (PAH), acute vasodilator response testing (AVT) is considered important to identify adult patients with favorable prognosis using calcium-channel blocker (CCB) therapy. However, in pediatric PAH, criteria used to identify acute responders and CCB use are

  4. TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension

    NARCIS (Netherlands)

    Kerstjens-Frederikse, Wilhelmina S.; Bongers, Ernie M. H. F.; Roofthooft, Marcus T. R.; Leter, Edward M.; Douwes, J. Menno; Van Dijk, Arie; Vonk-Noordegraaf, Anton; Dijk-Bos, Krista K.; Hoefsloot, Lies H.; Hoendermis, Elke S.; Gille, Johan J. P.; Sikkema-Raddatz, Birgit; Hofstra, Robert M. W.; Berger, Rolf M. F.

    Background Childhood-onset pulmonary arterial hypertension (PAH) is rare and differs from adult-onset disease in clinical presentation, with often unexplained mental retardation and dysmorphic features (MR/DF). Mutations in the major PAH gene, BMPR2, were reported to cause PAH in only 10-16% of

  5. Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry : A Candidate Clinical Endpoint

    NARCIS (Netherlands)

    Zijlstra, Willemijn M H; Ploegstra, Mark-Jan; Vissia-Kazemier, Theresia R; Roofthooft, Marcus T. R.; du Marchie Sarvaas, Gideon; Bartelds, Beatrijs; Rackowitz, Annette; van den Heuvel, Freek; Hillege, Hans L; Plasqui, Guy; Berger, Rolf M F

    2017-01-01

    Rationale: The development of evidence-based treatment guidelines for pediatric pulmonary arterial hypertension (PAH) is hampered by lack of pediatric clinical trials. Trial design is hampered by lack of a feasible clinical endpoint in this population. Objectives: To evaluate the use of

  6. Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

    Directory of Open Access Journals (Sweden)

    Bohn Olga L

    2012-11-01

    Full Text Available Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045.

  7. Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

    Science.gov (United States)

    2012-01-01

    Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045. PMID:23134683

  8. The importance of echocardiography in diagnostics of idiopathic pulmonary arterial hypertension: A case report

    Directory of Open Access Journals (Sweden)

    Stojković Gabrijela

    2011-01-01

    Full Text Available Introduction. Idiopathic pulmonary arterial hypertension (IPAH is rare and difficult progressive disease with prevalence of approximately 15 cases per million residents, with predominant female cases. Case Outline. A 47-year-old female presented with symptoms and signs of the right heart chambers failure. Over prior seven years the patient had the feeling of suffocation and fatigue when walking, and received treatment for bronchial asthma. Physical examination revealed a marked loud second heart sound over the pulmonary artery. Electrocardiogram: right ventricular hypertrophy. Spirometric (pulmonary capacity test, cardiac perfusion scan and spiral CT scanning excluded secondary pulmonary arterial hypertension. Blood testing for connective tissue diseases and HIV were within normal reference limits. Transthoracic colour Doppler echocardiography demonstrated a mild tricuspid regurgitation with high values of estimated maximal and middle systolic pressure of the right ventricle (135/110 mm Hg, and excluded previous heart disease. Cardiac catheterization confirmed IPAH diagnosis, with systolic right ventricular pressure of 101/47/66 mm Hg and pulmonary capillary pressure of 30/13/10 mm Hg. Basic therapy with sildenafil, nevertheless, considerable limitations of strain tolerance was still present. Conclusion. IPAH is a severe heart disease with non-specific signs and symptoms. Screening for IPAH is transthoracic colour Doppler echocardiography shows high correlation with cardiac catheterization.

  9. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Irene M. Lang

    2015-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.

  10. Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gautam V Ramani

    2010-05-01

    Full Text Available Gautam V Ramani, Myung H ParkUniversity of Maryland, Baltimore, MD, USAAbstract: Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH. The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. Keywords: sildenafil, pulmonary arterial hypertension, phosphodiesterase type 5 inhibitor

  11. Experimental and numerical studies of two arterial wall delamination modes.

    Science.gov (United States)

    Leng, Xiaochang; Zhou, Boran; Deng, Xiaomin; Davis, Lindsey; Lessner, Susan M; Sutton, Michael A; Shazly, Tarek

    2017-09-19

    Arterial wall dissection, which results from various pathophysiological processes, can lead to the occurrence of large area delamination in the aortic wall that can potentially block blood flow and lead to deleterious clinical conditions. Despite its critical clinical relevance, few studies have focused on investigating the failure mode of delamination in the arterial wall. In this study, we quantify the energy release rate of the medial layer of a porcine abdominal aorta via two delamination experiments: the mixed-mode delamination experiment and the "T"-shaped delamination experiment. A cohesive zone model (CZM) is applied to simulate the arterial wall delamination and Holzapfel-Gasser-Ogden (HGO) material model is used to capture the bulk arterial material behavior. A set of parameter values for the HGO and CZM models are identified through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements. Then the parameter values and critical energy release rates obtained from experiments are used as input data for simulation predictions for two arterial wall delamination experiments. The simulation predictions show that the delamination front matches well with experimental measurements. Moreover, the mixed-mode delamination experiment reveals a shear mode-dominated failure event, whereas the "T"-shaped delamination experiment is an opening failure process. The integration of experimental data and numerical predictions of arterial delamination events provides a comprehensive description of distinct failure modes and aids in the prediction of aortic dissection. Copyright © 2017. Published by Elsevier Ltd.

  12. Pulmonary artery dissection following balloon valvuloplasty in a dog with pulmonic stenosis.

    Science.gov (United States)

    Grint, K A; Kellihan, H B

    2017-04-01

    A 3-month-old, 9.9 kg, male pit bull cross was referred for evaluation of collapse. A left basilar systolic heart murmur graded V/VI and a grade IV/VI right basilar systolic heart murmur were ausculted. Echocardiography showed severe pulmonic stenosis characterized by annular hypoplasia, leaflet thickening, and leaflet fusion. After 1 month of atenolol therapy, a pulmonic valve balloon valvuloplasty procedure was performed, and the intra-operative right ventricular pressure was reduced by 43%. Echocardiography, performed the following day, showed apparent rupture of a pulmonary valve leaflet and a membranous structure within the pulmonary artery consistent with a dissecting membrane. Short-term follow-up has shown no apparent progression of the pulmonary artery dissection and the patient remains free of clinical signs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis.

    Science.gov (United States)

    Serra, Walter; Chetta, Alfredo; Santilli, Daniele; Mozzani, Flavio; Dall'Aglio, Pier Paolo; Olivieri, Dario; Cattabiani, Maria Alberta; Ardissino, Diego; Gherli, Tiziano

    2010-07-05

    Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO). Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of 0.05 was considered significant. Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 +/- 8 mmHg), whereas right ventricular function was normal (TAPSE 23 +/- 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01). Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.

  14. The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Lucchetta, Luca; Monge-Garcia, M Ignacio; Borges, Joao Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-03-01

    To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. Experimental study. Animal research laboratory. Ten pigs, 35 ± 5.2 kg. Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p mechanics compared with higher or lower positive end-expiratory pressure settings.

  15. Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.

    Science.gov (United States)

    Segura-Ibarra, Victor; Amione-Guerra, Javier; Cruz-Solbes, Ana S; Cara, Francisca E; Iruegas-Nunez, David A; Wu, Suhong; Youker, Keith A; Bhimaraj, Arvind; Torre-Amione, Guillermo; Ferrari, Mauro; Karmouty-Quintana, Harry; Guha, Ashrith; Blanco, Elvin

    2017-05-30

    Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model.

    Science.gov (United States)

    Chen, Yu-Cai; Yuan, Tian-Yi; Zhang, Hui-Fang; Wang, Dan-Shu; Yan, Yu; Niu, Zi-Ran; Lin, Yi-Huang; Fang, Lian-Hua; Du, Guan-Hua

    2016-06-01

    The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg(-1)·d(-1)) or a positive control bosentan (30 mg·kg(-1)·d(-1)) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.

  17. Induced Pluripotent Stem Cell Model of Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity.

    Science.gov (United States)

    Sa, Silin; Gu, Mingxia; Chappell, James; Shao, Ning-Yi; Ameen, Mohamed; Elliott, Kathryn A T; Li, Dan; Grubert, Fabian; Li, Caiyun G; Taylor, Shalina; Cao, Aiqin; Ma, Yu; Fong, Ryan; Nguyen, Long; Wu, Joseph C; Snyder, Michael P; Rabinovitch, Marlene

    2017-04-01

    Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies. Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns that differed from those in unused donor cells. We then investigated whether endothelial cells differentiated from pluripotent cells could serve as surrogates to test emerging therapies. Functional changes assessed included adhesion, migration, tube formation, and propensity to apoptosis. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and its target, collagen IV, signaling of the phosphorylated form of the mothers against decapentaplegic proteins (pSMAD1/5), and transcriptomic profiles were also analyzed. Native pulmonary arterial and induced pluripotent stem cell-derived endothelial cells from patients with idiopathic and heritable pulmonary arterial hypertension compared with control subjects showed a similar reduction in adhesion, migration, survival, and tube formation, and decreased BMPR2 and downstream signaling and collagen IV expression. Transcriptomic profiling revealed high kisspeptin 1 (KISS1) related to reduced migration and low carboxylesterase 1 (CES1), to impaired survival in patient cells. A beneficial angiogenic response to potential therapies, FK506 and Elafin, was related to reduced slit guidance ligand 3 (SLIT3), an antimigratory factor. Despite the site of disease in the lung, our study indicates that induced pluripotent stem cell-derived endothelial cells are useful surrogates to uncover novel features related to disease mechanisms and to better match patients to

  18. Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J.; Reed, William

    2007-01-01

    Background Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. Objectives The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. Methods We conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Results Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03). Conclusions Chronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. PMID:17687455

  19. Aortic and pulmonary artery calcification: An unusual manifestation of twin-to-twin transfusion syndrome

    Directory of Open Access Journals (Sweden)

    Sumitra Venkatesh

    2017-01-01

    Full Text Available Twin-to-twin transfusion syndrome (TTTS at times complicates monochorionic twin gestations, resulting in conditions ranging from discordant sizes to fetal demise of one baby. Various types of cardiac defects have been described in the recipient twin of this syndrome. Isolated great artery calcification, i.e. aortic and pulmonary artery calcification is one such uncommon condition associated with TTTS. Calcification of the walls of great vessels may be due to chronic vascular injury sustained as a result of circulatory volume overload in the recipient twin. It may also cause severe systemic hypertension and cardiomyopathy. An accurate diagnosis is important for an optimal follow-up and appropriate genetic counseling. We report a case of aortic and pulmonary artery calcification in association with TTTS.

  20. Pulmonary arterial wall disease in COPD and interstitial lung diseases candidates for lung transplantation.

    Science.gov (United States)

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Messeguer, Manuel López; Roman, Antonio

    2017-05-06

    Pulmonary hypertension (PH) associated with lung disease has the worst prognosis of all types of PH. Pulmonary arterial vasculopathy is an early event in the natural history of chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The present study characterized the alterations in the structure and function of the pulmonary arterial (PA) wall of COPD and ILD candidates for lung transplantation (LTx). A cohort of 73 patients, 63 pre-LTx (30 COPD, 33 ILD), and ten controls underwent simultaneous right heart catheterisation and intravascular ultrasound (IVUS). Total pulmonary resistance (TPR), capacitance (Cp), and the TPR-Cp relationship were assessed. PA stiffness and the relative area of wall thickness were estimated as pulse PA pressure/IVUS pulsatility and as [(external sectional area-intimal area)/external sectional area] × 100, respectively. Twenty-seven percent of patients had pulmonary arterial wedge pressure > 15 mmHg and were not analyzed. PA stiffness and the area of wall thickness were increased in comparison with controls, even in patients without PH (p < 0.05). ILD patients showed a significant higher PA stiffness, and lower Cp beyond mean PA pressure (mPAP) and lower area of wall thickness than COPD patients (p < 0.05). TPR-Cp relationship was shifted downward left for ILD patients. Significant increase of PA stiffness and area of wall thickness were present even in patients without PH and can make the diagnosis of pulmonary vasculopathy at a preclinical stage in PH-lung disease candidates for LTx. ILD patients showed the worst PA stiffness and Cp with respect to COPD.

  1. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.; Ji, Y.X.; Jiang, W.L.; Lv, C.J. [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai (China)

    2015-05-08

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC{sub 50} of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  2. Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension

    NARCIS (Netherlands)

    van Beers, Eduard J.; van Eck-Smit, Berthe L. F.; Mac Gillavry, Melvin R.; van Tuijn, Charlotte F. J.; van Esser, Joost W. J.; Brandjes, Dees P. M.; Kappers-Klunne, Mies C.; Duits, Ashley J.; Biemond, Bart J.; Schnog, John-John B.

    2008-01-01

    Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown.

  3. [Absent pulmonary valve syndrome with ductal origin of the left pulmonary artery. Diagnosis only by 2-D echo doppler color flow mapping].

    Science.gov (United States)

    Cazzaniga, M; Rico Gómez, F; Ros Pérez, P; Quero Jiménez, C; Rodríguez Vázquez del Rey, M

    2000-01-01

    A two-month old infant is described with the rare combination of absent pulmonary valve syndrome, ventricular septal defect, pulmonar "anular" stenosis and ductal origin of the left pulmonary artery. The diagnosis that was confirmed in the operating room was made by 2-D echocardiographic Doppler color flow mapping study without the support of cardiac catheterization.

  4. Iron Deficiency in COPD Associates with Increased Pulmonary Artery Pressure Estimated by Echocardiography

    DEFF Research Database (Denmark)

    Plesner, Louis L; Schoos, Mikkel M; Dalsgaard, Morten

    2017-01-01

    OBJECTIVES: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients....... METHODS: Non-anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin...0.05). Ferritin inversely correlated with TR Vmax in ID patients (-0.37 (p=0.04)). The prevalence of TR Vmax ≥ 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID...

  5. A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects

    Science.gov (United States)

    Gomez-Arroyo, Jose; Saleem, Sheinei J.; Mizuno, Shiro; Syed, Aamer A.; Bogaard, Harm J.; Abbate, Antonio; Taraseviciene-Stewart, Laimute; Sung, Yon; Kraskauskas, Donatas; Farkas, Daniela; Conrad, Daniel H.; Nicolls, Mark R.

    2012-01-01

    Many chronic pulmonary diseases are associated with pulmonary hypertension (PH) and pulmonary vascular remodeling, which is a term that continues to be used to describe a wide spectrum of vascular abnormalities. Pulmonary vascular structural changes frequently increase pulmonary vascular resistance, causing PH and right heart failure. Although rat models had been standard models of PH research, in more recent years the availability of genetically engineered mice has made this species attractive for many investigators. Here we review a large amount of data derived from experimental PH reports published since 1996. These studies using wild-type and genetically designed mice illustrate the challenges and opportunities provided by these models. Hemodynamic measurements are difficult to obtain in mice, and right heart failure has not been investigated in mice. Anatomical, cellular, and genetic differences distinguish mice and rats, and pharmacogenomics may explain the degree of PH and the particular mode of pulmonary vascular adaptation and also the response of the right ventricle. PMID:22307907

  6. Isquemia pulmonar embólica: aspectos clínicos e experimentais Pulmonary embolic ischemia: clinical and experimental aspects

    Directory of Open Access Journals (Sweden)

    Fabio Biscegli Jatene

    2003-09-01

    Full Text Available A isquemia está freqüentemente relacionada a mecanismos embólicos e esta oclusão arterial mecânica não é sempre seguida de conseqüências isquêmicas severas porque mudanças na circulação brônquica suprem as áreas sem fluxo sangüíneo. No entanto, ocorre o fenômeno de remodelação vascular, também relacionado a níveis elevados de pressão arterial pulmonar, principalmente no tromboembolismo pulmonar crônico. Modelos experimentais têm sido produzidos para estudar a relação entre a oclusão arterial mecânica, a hipertensão pulmonar e a remodelação vascular, entretanto mais avaliações sistemáticas são necessárias para se entender esta relação no parênquima pulmonar isquêmico e não isquêmico.Pulmonary ischemia is usually related with embolics mechanisms, and this mechanic artery occlusion is not always followed by severe ischemic consequences, because the bronchial circulation changes supply the areas without blood flow. However, small artery vascular remodeling occurs, related to persistent high pulmonary pressure levels, mainly in the chronic pulmonary thromboembolism. Experimental models have been produced to study the relation-ship between mechanic artery occlusion, pulmonary hypertension and vascular remodeling, however, more systematic evaluation is necessary to understand such a these relation-ship, in the ischemic and not ischemic lung parenchyma.

  7. A 50-year-old woman with haemoptysis, cough and tachypnea: cholesterol pneumonia accompanying with pulmonary artery hypertension.

    Science.gov (United States)

    Li, Mengxi; Zhang, Nuofu; Zhou, Ying; Li, Jinhui; Gu, Yingying; Wang, Jian; Liu, Chunli

    2017-03-01

    Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. Here we described a case of a 50-year-old woman with haemoptysis, cough and tachypnea, who was diagnosed with cholesterol pneumonia accompanying with pulmonary artery hypertension. The extremely high pulmonary artery pressure achieved, in this case, is alarming and should alert the physicians that the cholesterol pneumonia may be one of the underlying causes of pulmonary artery hypertension. After a treatment of methylprednisolone, her clinical symptoms were significantly improved, which suggested that steroid might be a promising therapeutic for patients with cholesterol pneumonia. © 2015 John Wiley & Sons Ltd.

  8. 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

  9. Computed tomography angiography with pulmonary artery thrombus burden and right-to-left ventricular diameter ratio after pulmonary embolism.

    Science.gov (United States)

    Ouriel, Kenneth; Ouriel, Richard L; Lim, Yeun J; Piazza, Gregory; Goldhaber, Samuel Z

    2017-02-01

    Purpose Computed tomography angiography is used for quantifying the significance of pulmonary embolism, but its reliability has not been well defined. Methods The study cohort comprised 10 patients randomly selected from a 150-patient prospective trial of ultrasound-facilitated fibrinolysis for acute pulmonary embolism. Four reviewers independently evaluated the right-to-left ventricular diameter ratios using the standard multiplanar reformatted technique and a simplified (axial) method, and thrombus burden with the standard modified Miller score and a new, refined Miller scoring system. Results The intraclass correlation coefficient for intra-observer variability was .949 and .970 for the multiplanar reformatted and axial methods for estimating right-to-left ventricular ratios, respectively. Inter-observer agreement was high and similar for the two methods, with intraclass correlation coefficient of .969 and .976. The modified Miller score had good intra-observer agreement (intraclass correlation coefficient .820) and was similar to the refined Miller method (intraclass correlation coefficient .883) for estimating thrombus burden. Inter-observer agreement was also comparable between the techniques, with intraclass correlation coefficient of .829 and .914 for the modified Miller and refined Miller methods. Conclusions The reliability of computed tomography angiography for pulmonary embolism was excellent for the axial and multiplanar reformatted methods for quantifying the right-to-left ventricular ratio and for the modified Miller and refined Miller scores for quantifying of pulmonary artery thrombus burden.

  10. Anomalous origin of the left coronary artery from the pulmonary artery in an elderly patient, football player in youth.

    Science.gov (United States)

    Facciorusso, Antonio; Lanna, Pompeo; Vigna, Carlo; Massaro, Raimondo; Stanislao, Mario; Santoro, Tiberio; Valle, Guido; Carbone, Carmine; Grilli, Gian Paolo; Fanelli, Raffaele

    2008-10-01

    Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital defect. Without surgical treatment, approximately 90% of infants die within the first year of life. Late presentation in the adult or elderly is rare. Factors that may lead to survival in advanced age include the development of intercoronary collaterals. Furthermore, the risk of sudden cardiac death due to ischaemic malignant ventricular dysrhythmias exists even in asymptomatic adult patients and, classically, is precipitated by exercise. We report the case of a 67-year-old man, a football player in his youth, always asymptomatic until presentation at our centre for symptomatic sustained ventricular tachycardia and shortness of breath on exertion. We show the features of the ECG, transthoracic echocardiography, angiography study of the coronary and the pulmonary system, myocardial basal and stress gated single photon emission computed tomography with Tc-tetrofosmin and cardiac CT 64 slices. The patient was referred to cardiac surgery. We believe that this patient's favourable course may be ascribed to the large network of collaterals from the right coronary artery supplying the entire heart. However, the exact reason why these favourable evolutions (both vascular and clinical) occur only in some individuals remains largely unknown.

  11. Hybrid pulmonary valve implantation: injection of a self-expanding tissue valve through the main pulmonary artery.

    Science.gov (United States)

    Dittrich, Sven; Gloeckler, Martin; Arnold, Raoul; Sarai, Koppany; Siepe, Matthias; Beyersdorf, Friedhelm; Schlensak, Christian

    2008-02-01

    An 8-year-old (35 kg) boy presented with progressive right ventricular outflow tract enlargement (28 mm) and progressive tricuspid regurgitation after transannular repair of tetralogy of Fallot and was scheduled for pulmonary valve replacement. To spare reoperation on full sternotomy, a transverse mini-thoracotomy through the third intercostal space was used to implant an injectable 29-mm stented porcine valve directly through an incision of the pulmonary artery bifurcation. The procedure was performed while rapid ventricular pacing and right ventricular unload by a short running femorally implanted cardiopulmonary bypass. The stented valve was fixed with three single sutures to avoid embolization. The interventional result was well with full competence of the valve. The boy was discharged at day 4 after the procedure.

  12. Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome.

    Science.gov (United States)

    Miwa, Kenji; Matsubara, Takashi; Uno, Yoshihide; Yasuda, Toshihiko; Sakata, Kenji; Tsuda, Toyonobu; Kanaya, Honin

    2007-05-01

    Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.

  13. Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Pugliese SC

    2016-01-01

    Full Text Available Steven C Pugliese,1 Todd M Bull1,2 1Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, 2UCD Pulmonary Vascular Disease Center, Division of Pulmonary Sciences and Critical Care Medicine and Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH. Intravenous (IV epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin. Recent Phase III clinical trials have shown the drug to improve exercise tolerance in treatment-naïve PAH patients, but not patients on background oral therapy. Oral treprostinil appears to be most efficacious at higher doses, but its side effect profile and complexities with dosing complicate its use. While oral treprostinil’s current therapeutic role in PAH remains unclear, ongoing studies of this class of medication should help clarify their role in the treatment of PAH. Keywords: oral treprostinil, pulmonary arterial hypertension, selexipag

  14. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

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    Tselios K

    2016-12-01

    Full Text Available Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, ON, Canada Abstract: Systemic lupus erythematosus (SLE is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH, after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg with normal pulmonary capillary wedge pressure (≤15 mmHg and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan, phosphodiesterase type 5 inhibitors (sildenafil, and vasodilators (epoprostenol. Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively. Keywords: systemic lupus erythematosus, pulmonary arterial hypertension, immunosuppressive, transthoracic echocardiogram, endothelin receptor antagonists

  15. Hypoxia and nitric oxide exposure promote apoptotic signaling in contractile pulmonary arterial smooth muscle but not in pulmonary epithelium.

    Science.gov (United States)

    Postolow, F; Fediuk, J; Nolette, N; Hinton, M; Dakshinamurti, S

    2011-12-01

    Neonatal pulmonary hypertension is characterized by hypoxia, abnormal vascular remodeling, and impaired alveolarization. Nitric oxide (NO) regulates cell replication and activation of apoptosis. Our objective was to examine cell phenotype-specific effects of hypoxia and NO exposure on cumulative apoptotic signal in neonatal pulmonary epithelial cells and arterial smooth muscle. Primary cultured newborn porcine pulmonary arterial myocytes and epithelial cells were grown in normoxic (21% O2) or hypoxic conditions (10% O2). Myocyte phenotype was predetermined by serum-supplementation or -deprivation. Cells were exposed to sodium nitroprusside (10(-7) -10(-4)  M) or diluent for 3 days. Cell survival was estimated by MTT assay; BAX, Bcl-2, and cleaved caspase-3 by Western blot; cell cycle entry by laser scanning cytometry. Hypoxic epithelial cells exhibited a small increase in anti-apoptotic Bcl2, and decrease in BAX. Cell survival and active caspase-3 were unchanged. Exposure to NO had no impact on epithelial apoptosis, but initiated necrosis. In contractile myocytes, pro-apoptotic BAX abundance and caspase-3 activation were increased by hypoxia, augmented by NO exposure promoting apoptosis. Hypoxia decreased BAX/Bcl-2 ratio and promoted survival of synthetic myocytes; NO increased apoptosis of normoxic synthetic myocytes, but decreased apoptosis of hypoxic synthetic myocytes. The effect of NO on pulmonary apoptosis is phenotype-dependent. A cumulative apoptotic effect of hypoxia and NO in vitro exerted on contractile myocytes may lead to contraction of this subpopulation, while synthetic myocyte survival and proliferation is enhanced by hypoxia and NO. Epithelial survival is unaffected. We speculate that alveolar rarefaction reported after neonatal hypoxia may arise from growth arrest in the vascular rather than the epithelial compartment. Copyright © 2011 Wiley Periodicals, Inc.

  16. Anomalous origin of the right pulmonary artery from the abdominal aorta with aberrant right subclavian artery and left patent ductus arteriosus.

    Science.gov (United States)

    Fu, Songling; Xie, Chunhong; Gong, Fangqi; Zhu, Weihua

    2011-06-01

    Anomalous origin of the pulmonary artery (AOPA) from the aorta is a rare congenital heart malformation. This report describes a case of AOPA from the abdominal aorta in association with an aberrant right subclavian artery and a patent ductus arteriosus, which never has been reported previously in the literature.

  17. Astragalus Polysaccharides Attenuate Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats.

    Science.gov (United States)

    Yuan, Lin-Bo; Hua, Chun-Yan; Gao, Sheng; Yin, Ya-Ling; Dai, Mao; Meng, Han-Yan; Li, Piao-Piao; Yang, Zhong-Xin; Hu, Qing-Hua

    2017-01-01

    Astragalus polysaccharides (APS) have been shown to possess a variety of biological activities including anti-oxidant and anti-inflammation functions in a number of diseases. However, their function in pulmonary arterial hypertension (PAH) is still unknown. Rats received APS (200[Formula: see text]mg/kg once two days) for 2 weeks after being injected with monocrotaline (MCT; 60[Formula: see text]mg/kg). The pulmonary hemodynamic index, right ventricular hypertrophy, and lung morphological features of the rat models were examined, as well as the NO/eNOS ratio of wet lung and dry lung weight and MPO. A qRT-PCR and p-I[Formula: see text]B was used to assess IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] and WB was used to detect the total I[Formula: see text]B. Based on these measurements, it was found that APS reversed the MCT-induced increase in mean pulmonary arterial pressure (mPAP) (from 32.731[Formula: see text]mmHg to 26.707[Formula: see text]mmHg), decreased pulmonary vascular resistance (PVR) (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text] min/L to 246.351[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L), and reduced right ventricular hypertrophy (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L to 246.351 mmHg[Formula: see text][Formula: see text][Formula: see text]min/L) ([Formula: see text]0.05). In terms of pulmonary artery remodeling, the WT% and WA% decreased with the addition of APS. In addition, it was found that APS promoted the synthesis of eNOS and the secretion of NO, promoting vasodilation and APS decreased the MCT-induced elevation of MPO, IL-1[Formula: see text], IL-6 and TNF-[Formula: see text], reducing inflammation. Furthermore, APS was able to inhibit the activation of pho-I[Formula: see text]B[Formula: see text]. In couclusion, APS ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial

  18. Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways.

    Science.gov (United States)

    Grzegorzewska, Agnieszka P; Seta, Francesca; Han, Rong; Czajka, Caitlin A; Makino, Katsunari; Stawski, Lukasz; Isenberg, Jeffrey S; Browning, Jeffrey L; Trojanowska, Maria

    2017-02-02

    Pulmonary arterial hypertension (PAH) is a fatal condition for which there is no cure. Dimethyl Fumarate (DMF) is an FDA approved anti-oxidative and anti-inflammatory agent with a favorable safety record. The goal of this study was to assess the effectiveness of DMF as a therapy for PAH using patient-derived cells and murine models. We show that DMF treatment is effective in reversing hemodynamic changes, reducing inflammation, oxidative damage, and fibrosis in the experimental models of PAH and lung fibrosis. Our findings indicate that effects of DMF are facilitated by inhibiting pro-inflammatory NFκB, STAT3 and cJUN signaling, as well as βTRCP-dependent degradation of the pro-fibrogenic mediators Sp1, TAZ and β-catenin. These results provide a novel insight into the mechanism of its action. Collectively, preclinical results demonstrate beneficial effects of DMF on key molecular pathways contributing to PAH, and support its testing in PAH treatment in patients.

  19. Exercise training attenuates right ventricular remodeling in rats with pulmonary arterial stenosis

    Directory of Open Access Journals (Sweden)

    Brunno Lemes

    2016-12-01

    Full Text Available Introduction: Pulmonary arterial stenosis (PAS is a congenital defect that causes outflow tract obstruction of the right ventricle (RV. Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks. Methods & Results: Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt1 activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling - ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance. Conclusion: Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility.

  20. Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Brittain, Evan L; Talati, Megha; Fessel, Joshua P; Zhu, He; Penner, Niki; Calcutt, M Wade; West, James D; Funke, Mitch; Lewis, Gregory D; Gerszten, Robert E; Hamid, Rizwan; Pugh, Meredith E; Austin, Eric D; Newman, John H; Hemnes, Anna R

    2016-05-17

    The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH. We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4±1.3% triglyceride versus 0.22±0.11% triglyceride, P=0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV. Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation. © 2016 American Heart Association, Inc.

  1. Cognitive, emotional, and quality of life outcomes in patients with pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Glissmeyer Eric W

    2006-03-01

    Full Text Available Abstract Background The effects of pulmonary arterial hypertension on cardiovascular and physical function are well documented. Limited information exists regarding the effects of pulmonary arterial hypertension on cognitive function despite patient reports of problems with memory and attention. Our primary purpose was to determine if a prospectively identified cohort of pulmonary arterial hypertension patients had cognitive sequelae. Our secondary purpose was to determine the relationships between cognitive sequelae and neuropsychological test scores with depression, anxiety, and quality of life. Methods Forty-six adults with pulmonary arterial hypertension underwent assessment of cognitive function, depression, anxiety, and quality of life using standardized neuropsychological tests and questionnaires. The patients' scores were compared to normal population data. Medical, affective, neuropsychological, and quality of life data for patients with and without cognitive sequelae were compared using analysis of variance, Chi-square, or Fisher exact tests for categorical data. Correlations assessed relationships between neuropsychological test scores, depression, anxiety, quality of life, and medical data. Results Cognitive sequelae occurred in 58% (27/46 of the pulmonary arterial hypertension patients. Patients with cognitive sequelae had worse verbal learning, delayed verbal memory, executive function, and fine motor scores compared to patients without cognitive sequelae. Twenty-six percent of patients had moderate to severe depression and 19% had moderate to severe anxiety. Depression, anxiety and quality of life were not different for patients with or without cognitive sequelae. Our patients had decreased quality of life, which was associated with worse working memory. Conclusion Patients with pulmonary arterial hypertension have cognitive impairments, depression, anxiety, and decreased quality of life. Depression, anxiety, and quality of life

  2. [Hyperlucent lung syndrom caused by pulmonary artery hypoplasia in patient with diagnosed asthma--case report].

    Science.gov (United States)

    Górska, Lucyna; Kuziemski, Krzysztof; Wajda, Beata; Damps-Konstańska, Iwona; Tokarska, Beata; Jassem, Ewa

    2008-05-01

    We present case of 67-years-old, non-smoking woman with unilateral hyperlucent lung syndrome. She has diagnosed asthma and since 1997 she has been treated with inhaled corticosteroids and long-acting beta-agonists without improvement. She complained of a cough, shortness of breath, pulmonary function test reveal irrvesibility airflow obstruction. The routine X-ray chest showed unilateral hyperlucent left lung. Ct-angiography has shown unilateral hypoplasia of pulmonary artery. It indicates that in all cases of uncontrolled asthma should be considered another or coexisting diagnosis.

  3. Rapid Fatal Outcome from Pulmonary Arteries Compression in Transitional Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ioannis A. Voutsadakis

    2009-01-01

    Full Text Available Transitional cell carcinoma of the urinary bladder is a malignancy that metastasizes frequently to lymph nodes including the mediastinal lymph nodes. This occurrence may produce symptoms due to compression of adjacent structures such as the superior vena cava syndrome or dysphagia from esophageal compression. We report the case of a 59-year-old man with metastatic transitional cell carcinoma for whom mediastinal lymphadenopathy led to pulmonary artery compression and a rapidly fatal outcome. This rare occurrence has to be distinguished from pulmonary embolism, a much more frequent event in cancer patients, in order that proper and prompt treatment be initiated.

  4. Missed diagnosis of atresia of the right pulmonary artery in woman with left-sided pneumothorax

    DEFF Research Database (Denmark)

    Dagnegård, Hanna; Ryom, Philip

    2016-01-01

    Isolated pulmonary atresia is an uncommon condition, which can go undiagnosed for a long time in asymptomatic patients. Sometimes, diagnosis can be made at pregnancy due to respiratory symptoms. There is no known increased risk of pneumothorax. We here present a case where a second-time pregnant...... woman with an unknown atresia of the right pulmonary artery received a left-sided pneumothorax. The diagnosis was initially missed in spite of adequate imaging and the condition progressed to respiratory stop. We describe the course of diagnostics and the chosen strategy of treatment....

  5. 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.

  6. Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding

    Directory of Open Access Journals (Sweden)

    Marcos Danillo P. Oliveira

    2016-01-01

    Full Text Available Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae.

  7. Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding.

    Science.gov (United States)

    Oliveira, Marcos Danillo P; de Melo, Pedro H M Craveiro; Abreu-Silva, Érlon O; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

    2016-01-01

    Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae.

  8. Characterization of 5-HT receptors on human pulmonary artery and vein: functional and binding studies

    Science.gov (United States)

    Cortijo, Julio; Martí-Cabrera, Miguel; Bernabeu, Eva; Domènech, Teresa; Bou, Josep; Fernández, Andrés G; Beleta, Jorge; Palacios, José M; Morcillo, Esteban J

    1997-01-01

    This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), α-methyl 5-HT (α-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists.All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (−log EC50 values) was ergotamine (6.88)>5-HT (6.41)⩾SCMGT (6.20)=sumatriptan (6.19) ⩾α-Me (6.04) in the artery, and ergotamine (7.84)>5-HT (6.96)>sumatriptan (6.60)=α-Me (6.56)>SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5-HT were similar in intact and endothelium-denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium.GR127935 (1 nM to 0.5 μM) produced an unsurmountable antagonism of the response to 5-HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 μM) also reduced the maximum contractile responses to 5-HT, ergotamine and α-Me in artery and vein preparations without affecting those to sumatriptan and SCMGT. In endothelium-denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of α-Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pKB values of GR127935 (9.17±0.11 in artery and 9.11±0.05 in vein) and ritanserin (8.82±0.09 in artery and 8.98±0.12 in vein).WAY100635 (1 nM to 1 μM), zacopride (1 nM to 1 μM), or SB204070 (1 nM) did not significantly alter the concentration-response curves for 5-HT, sumatriptan, ergotamine, SCMGT or 2-Me in human pulmonary artery or vein thus indicating that 5-HT1A, 5-HT3 and 5-HT4 receptors are

  9. Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension

    NARCIS (Netherlands)

    Ruiter, G.; Wong, Y.Y.; de Man, F.S.; Handoko, M.L.; Jaspers, R.T.; Postmus, P.E.; Westerhof, N.; Niessen, H.W.M.; van der Laarse, W.J.; Vonk Noordegraaf, A.

    2013-01-01

    Background: In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined

  10. Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Duncan; Hollingworth, Greg; Soldermann, Nicolas; Sprague, Elizabeth; Schuler, Walter; Vangrevelinghe, Eric; Duggan, Nicholas; Thomas, Matthew; Kosaka, Takatoshi; Waters, Nigel; van Eis, Maurice J.

    2014-10-01

    A novel class of selective inhibitors of ROCK1 and ROCK2 has been identified by structural based drug design. PK/PD experiments using a set of highly selective Rho kinase inhibitors suggest that systemic Rho kinase inhibition is linked to a reversible reduction in lymphocyte counts. These results led to the consideration of topical delivery of these molecules, and to the identification of a lead molecule 7 which shows promising PK and PD in a murine model of pulmonary hypertension after intra-tracheal dosing.

  11. Pulmonary Arterial Hypertension With Abnormal V/Q Single-Photon Emission Computed Tomography.

    Science.gov (United States)

    Chan, Kenneth; Ioannidis, Stefanos; Coghlan, John G; Hall, Margaret; Schreiber, Benjamin E

    2017-10-16

    This study aimed to evaluate the incidence and clinical outcomes of abnormal ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) without thromboembolism, especially in patients with group I pulmonary arterial hypertension (PAH). American Heart Association/American College of Cardiology and European Society of Cardiology guidelines recommend V/Q scan for screening for chronic thromboembolic pulmonary hypertension. The significance of patients with abnormal V/Q SPECT findings but no thromboembolism demonstrated in further investigations remained unclear. A distinct pattern of global patchy changes not typical of thromboembolism is recognized, but guidelines for reporting these in the context of PAH are lacking. A total of 136 patients who underwent V/Q SPECT and right-sided heart catheterization showing mean pulmonary arterial pressure ≥25 mm Hg were included. V/Q SPECT findings were reported using European Association of Nuclear Medicine criteria for pulmonary embolism followed by computed tomography pulmonary angiography screening for positive thromboembolism and further invasive pulmonary angiography for distal thromboembolism. The abnormal V/Q SPECT images were further analyzed according to perfusion pattern into focal or global perfusion defects. V/Q SPECT showed thromboembolic disease in 44 patients, but 19 of these patients had no thromboembolism demonstrated by pulmonary angiography. Among these patients, 15 of 19 (78.9%) had group I PAH, and the majority had diffuse, patchy perfusion defects. After redefining V/Q SPECT images according to the perfusion pattern, those patients with global perfusion defects had higher mean pulmonary arterial pressure compared with patients with focal perfusion defects and normal scans (mean difference +13.9 and +6.2 mm Hg, respectively; p = 0.0002), as well as higher pulmonary vascular resistance (mean difference +316.6 and +226.3 absolute resistance units, respectively; p = 0

  12. Sudden cardiac death as a presentation of anomalous origin of the left coronary artery from pulmonary artery in a young adult.

    Science.gov (United States)

    Pachon, Ronald; Bravo, Claudio; Niemiera, Mark

    2015-12-01

    Sudden cardiac death in 5-10% of cases is explained by patients with congenital abnormalities that include coronary artery malformations such as anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). We report a case of sudden cardiac death as the first presentation of ALCAPA in a young female with no history of hypertrophic cardiomyopathy. © The European Society of Cardiology 2014.

  13. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    Directory of Open Access Journals (Sweden)

    Salvatore Rosanio

    2014-01-01

    Full Text Available This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

  14. [Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by up-regulating heme oxygenase-1 expression].

    Science.gov (United States)

    Zhang, Yukun; Wang, Daoxin; Zhu, Tao; Li, Changyi

    2012-02-01

    To study the effect of genistein on the expression of heme oxygenase-1 (HO-1) in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Sixty male Sprague-Dawley rats were randomly divided into 4 groups (n=15), namely the control group, model group, low-dose (20 µg/kg) genistein group and high-dose (80 µg/kg) genistein group. The hemodynamic parameters were measured and the remodeling of pulmonary small arteries was observed by electron microscope (EM). The expression of HO-1 in the lung tissues were detected by Western blotting. Compared with the model group, genistein treatment significantly reduced the elevated mean pulmonary arterial pressure, improved the right ventricular hypertrophy index, and increased the expression of HO-1 in a dose-dependent manner. Genistein attentuates pulmonary arterial hypertension in MCT-treated rats possibly by up-regulation of HO-1 in the lung tissues.

  15. Coarctation of the Aorta with Aortic Arch Hypoplasia: Midterm Outcomes of Aortic Arch Reconstruction with Autologous Pulmonary Artery Patch

    Directory of Open Access Journals (Sweden)

    Zhi-Ling Ma

    2017-01-01

    Conclusion: AA reconstruction with coarctation resection and aortoplasty with autologous pulmonary artery patch could effectively correct CoA with AAH, and the rate of reintervention for restenosis is low.

  16. Anomalous origin of the right coronary artery from the pulmonary artery: an autopsied sudden death case with severe atherosclerotic disease of the left coronary artery.

    Science.gov (United States)

    Nagai, T; Mukai, T; Takahashi, S; Takada, A; Saito, K; Harada, K; Mori, S; Abe, N

    2014-03-01

    Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare anomaly. It may contribute to myocardial ischemia or sudden death, although the lesion is usually asymptomatic. We report a sudden death case of a 58-year-old man with ARCAPA coexisting with severe atherosclerotic coronary artery disease. He had been healthy until he complained of chest pain, several days before death, despite the discovery of heart murmur in childhood and suspicion of valvular heart disease. The autopsy revealed not only typical findings of the right coronary anomaly with well-developed collateral circulations but also severe atherosclerotic lesions of the left coronary artery, and ischemic change of the myocardium in the left and right coronary arterial perfusion territory. In addition to the "coronary steal" phenomenon primarily caused by ARCAPA, the reduced flow of both coronary arteries and further increase of "coronary steal" due to atherosclerotic obstructive coronary disease might have contributed to the patient's death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Successful Interventional Management for Pulmonary Arterial Injury Secondary to Pacemaker Implantation

    Directory of Open Access Journals (Sweden)

    Hiroyuki Tokue

    2016-01-01

    Full Text Available Subclavian vein puncture is a relatively fast and safe technique to access the right heart for placement of pacemaker leads. Hemothorax related to injury of the pulmonary artery (PA is a rare complication of subclavian vein access but can be life-threatening. We report a case of hemothorax occurring after subclavian vein puncture for pacemaker implantation. No cases of transcatheter arterial embolization for PA injury secondary to pacemaker implantation have been reported. Understanding of this rare complication after pacemaker implantation along with its specific clinical presentation may lead to early diagnosis and intervention.

  18. Arteriovenous Fistula after Femoral Artery Puncture Leading to Pulmonary Edema: The Role of Ultrasonography

    Directory of Open Access Journals (Sweden)

    Jan Malík

    2012-01-01

    Full Text Available Local complications of arterial puncture include hematoma, pseudoaneurysm and formation of arteriovenous fistula (AVF. The latter could cause ischemia of the particular extremity or can be hemodynamically significant especially in patients suffering from congestive heart failure. We report a case of femoro-femoral AVF after thin needle arterial puncture for blood drawing. The development of this iatrogenic AVF led to pulmonary edema. The patient stabilized completely after surgical closure of the AVF. The AVF was diagnosed by duplex Doppler ultrasonography and this method was also used for estimation of blood flow through the AVF. We discuss the role of ultrasound AVF diagnostics and the method of flow calculation.

  19. Early Manifestation of Supravalvular Aortic and Pulmonary Artery Stenosis in a Patient with Williams Syndrome

    Directory of Open Access Journals (Sweden)

    Jong Uk Lee

    2016-04-01

    Full Text Available Williams syndrome (WS is a developmental disorder characterized by vascular abnormalities such as thickening of the vascular media layer in medium- and large-sized arteries. Supravalvular aortic stenosis (SVAS and peripheral pulmonary artery stenosis (PPAS are common vascular abnormalities in WS. The natural course of SVAS and PPAS is variable, and the timing of surgery or intervention is determined according to the progression of vascular stenosis. In our patient, SVAS and PPAS showed rapid concurrent progression within two weeks after birth. We report the early manifestation of SVAS and PPAS in the neonatal period and describe the surgical treatment for stenosis relief.

  20. Covered Stent and Coils Embolization of a Pulmonary Artery Pseudoaneurysm After Gunshot Wound

    Energy Technology Data Exchange (ETDEWEB)

    Huet, Nicolas, E-mail: nhuet@chu-grenoble.fr; Rodiere, Mathieu, E-mail: mrodiere@chu-grenoble.fr [Hôpital Universitaire de Grenoble and Université Grenoble Alpes, Department of Radiology and Medical Imaging (France); Badet, Michel, E-mail: michel.badet@ch-chambery.fr [Centre Hospitalier Métropôle Savoie, site de Chambéry, Intensive Care Unit (France); Michoud, Marie, E-mail: marie.michoud@ch-chambery.fr [Centre Hospitalier Métropôle Savoie, Site de Chambéry, Department of Radiology (France); Brichon, Pierre-Yves, E-mail: pybrichon@chu-grenoble.fr [Hôpital Universitaire de Grenoble and Université Grenoble Alpes, Department of Thoracic and Vascular Surgery (France); Ferretti, Gilbert, E-mail: gferretti@chu-grenoble.fr; Thony, Frédéric, E-mail: fthony@chu-grenoble.fr [Hôpital Universitaire de Grenoble and Université Grenoble Alpes, Department of Radiology and Medical Imaging (France)

    2016-05-15

    We report the first case of endovascular covered stent implantation for the treatment of a large pulmonary artery pseudoaneurysm (PAPA) following a right thoracic gunshot wound. After resuscitation and hemodynamic stabilization, a CT angiography was performed to analyze the neck size of the PAPA and its position relative to the branches of the parent artery. Covered stent implantation with additional coil embolization was successfully performed. At the 4-year follow-up, the stents remained patent and there was neither pseudoaneurysm recurrence nor treatment-related complication.

  1. Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

    Directory of Open Access Journals (Sweden)

    J.H.T. Ferreira

    2006-09-01

    Full Text Available The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 ± 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 ± 8.64 to 39.14 ± 6.77 mmHg and alveolar air (from 92.97 ± 2.14 to 63.91 ± 8.27 mmHg. The effective alveolar ventilation exhibited a significant reduction (from 199.62 ± 42.01 to 84.34 ± 44.13 consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio also presented a significant reduction after embolization (from 0.96 ± 0.34 to 0.33 ± 0.17 fraction. The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 ± 1.71 to 60.76 ± 6.62 mmHg, but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 ± 1.22 to 23.15 ± 8.24 mmHg. Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 ± 1.36 to 37.61 ± 12.79 mmHg, as also did the calculated alveolar (from 56.38 ± 22.47 to 178.09 ± 37.46 mL and physiological (from 0.37 ± 0.05 to 0.75 ± 0.10 fraction dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution

  2. Multi-detector CT coronary angiographic findings of coronary-to-pulmonary artery fistula

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Jae Seok; Park, Eun Ah; Lim, Ji Yeon; Lee, Whal [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Park, Jae Hyung [Dept. of Radiology, Myongji Hospital, Seonam University College of Medicine, Goyang (Korea, Republic of)

    2017-01-15

    To evaluate multi-detector CT (MDCT) coronary angiographic findings of coronary-to-pulmonary artery fistula (CPAF). We retrospectively reviewed images of patients with CPAF from the coronary CT angiography (CCTA) database obtained with a 64-channel MDCT between January 2008 and March 2011. We analyzed the CCTA findings for feeding arteries, fistula, association with peripulmonary arterial aneurysms, and the presence of communication between the CPAF and bronchial arteries. Fifty-five of the 15042 (0.37%) patients were diagnosed with CPAFs. The feeding artery was single (n = 18) or multiple (n = 37). The fistula had a single drainage site (n = 54) or multiple drainage sites (n = 1). The mean diameter of the fistulous opening was 2.7 ± 1.4 mm. A peripulmonary arterial aneurysm was present in 24 (44%) patients. Communication between CPAF and bronchial arteries was present in eight (14.5%) patients. MDCT coronary angiography can provide comprehensive morphologic details on CPAF and may help in presurgical or preinterventional planning.

  3. Identification of G-Protein-Coupled-Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as Novel Therapeutic Targets

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0372 TITLE: Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as...DATES COVERED 2 Sep 2015 - 1Sep2016 4. TITLE AND SUBTITLE Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells ...smooth muscle cells (PASMCs). The underlying idea of this project is that the currently limited treatments for PAH represent an unmet medical need

  4. Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

    Directory of Open Access Journals (Sweden)

    Shian Huang

    2017-01-01

    Full Text Available This study aimed to investigate the effects and mechanisms of quercetin on pulmonary arterial endothelial cell (PAEC transdifferentiation into smooth muscle-like cells. TGF-β1-induced PAEC transdifferentiation models were applied to evaluate the pharmacological actions of quercetin. PAEC proliferation was detected with CCK8 method and BurdU immunocytochemistry. Meanwhile, the identification and transdifferentiation of PAECs were determined by FVIII immunofluorescence staining and α-SMA protein expression. The related mechanism was elucidated based on the levels of Akt and Erk1/2 signal pathways. As a result, quercetin effectively inhibited the TGF-β1-induced proliferation and transdifferentiation of the PAECs and activation of Akt/Erk1/2 cascade in the cells. In conclusion, quercetin is demonstrated to be effective for pulmonary arterial hypertension (PAH probably by inhibiting endothelial transdifferentiation possibly via modulating Akt and Erk1/2 expressions.

  5. Anomalous Origin of One Pulmonary Artery Branch From the Aorta: Role of MDCT Angiography.

    Science.gov (United States)

    Liu, Hui; Juan, Yu-Hsiang; Chen, Jimei; Xie, Zhaofeng; Wang, Qiushi; Zhang, Xiaoshen; Liang, Changhong; Huang, Hongfei; Kwong, Raymond Y; Saboo, Sachin S

    2015-05-01

    The purpose of this study was to evaluate the prevalence, MDCT angiography (MDCTA) appearance, associated congenital cardiovascular abnormalities, and prognosis of anomalous origin of one pulmonary artery from the aorta (AOPA) on the basis of MDCTA. We conducted a retrospective search of patients with AOPA from our database in a single center, consisting of 5729 patients referred for MDCTA with known or suspected congenital heart diseases from transthoracic echocardiography. The clinical information, subtypes of AOPA, associated cardiovascular anomalies, and surgical and clinical outcomes were retrospectively collected and analyzed. The MDCTA images were retrospectively processed for analysis, and the MDCTA and echocardiography images were interpreted by radiologist and cardiologist without knowledge of the actual diagnosis or surgical outcome. AOPA was seen in 19 patients (14 males and five females; median age, 3 months; range, 4 days-21 years) showing a prevalence of 0.33%. Anomalous origin of the right pulmonary artery (AORPA, 89%), proximal origin subtype of the AOPA (89%), and ipsilateral aortic wall origin of AOPA (58%) were more commonly seen. In addition to the benefit of preoperative planning, MDCTA also supplemented echocardiography by providing accurate diagnosis of AOPA and other associated cardiovascular anomalies compared with transthoracic echocardiography (TTE). We found a total of four patients (21%) with misdiagnosis by TTE, including three patients with underdiagnosis of AOPA and one patient with misdiagnosis as transposition of the great arteries. In addition, two other patients had AOPA diagnosed, but the associated patent ductus arteriosus (PDA) was not detected. MDCTA revealed 95% association with other congenital cardiovascular anomalies, including PDA (71% of AORPA), and aortic arch anomalies (100% of anomalous origin of the left pulmonary artery, AOLPA). The types of surgery depended on the MDCTA findings, including the sub-type, origin

  6. Gene Variant of the Bradykinin B2 Receptor Influences Pulmonary Arterial Pressures in Heart Failure Patients.

    Science.gov (United States)

    Olson, Thomas P; Frantz, Robert P; Turner, Stephen T; Bailey, Kent R; Wood, Christina M; Johnson, Bruce D

    2009-01-01

    Pulmonary arterial pressure (PAP) varies considerably in heart failure (HF) despite similar degrees of left ventricular (LV) dysfunction. Bradykinin alters vascular tone and common variations in the kinin B2 receptor (BDKRB2) gene exists. We hypothesized that genetic variation in this receptor would influence PAP in HF. 131 HF patients (>1yr history systolic HF), without COPD, not currently smoking, BMI tone in stable HF.

  7. Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease

    OpenAIRE

    Myers, Patrick Olivier; Tissot-Daguette, Cécile; Beghetti, Maurice

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease, and is now predominantly among patients with uncorrected left-to-right shunts. A growing population is characterized by persistent or recurrent PAH after surgical or interventional correction of left-to-right shunts; the latter having a worse prognosis than other forms of PAH associated with congenital heart disease. New treatments for PAH have been shown to be effective in improving PAH exercise capac...

  8. Status of Systemic To Pulmonary Arterial Collateral Flow After the Fontan Procedure

    OpenAIRE

    Whitehead, Kevin K.; Harris, Matthew A.; Glatz, Andrew C.; Gillespie, Matthew J.; DiMaria, Michael V.; Harrison, Neil E.; Dori, Yoav; Keller, Marc S.; Rome, Jonathan J.; Fogel, Mark A.

    2015-01-01

    We recently validated a method of quantifying systemic to pulmonary arterial collateral flow using phase-contrast magnetic resonance imaging velocity mapping (PC-MRI). Cross-sectional data suggest decreased collateral flow in patients with total cavopulmonary connections (TCPC) compared to those with superior cavopulmonary connections (SCPC). However, no studies have examined serial changes in collateral flow from SCPC to TCPC in the same patients. We sought to examine differences in collater...

  9. Lymphangiomatosis Involving the Inferior Vena Cava, Heart, Pulmonary Artery and Pelvic Cavity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hun; Seo, Hye Sun; Seo, Jon; Kim, Hee Kyung; Her, Keun [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Suk, Eun Ha [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2010-02-15

    A 38-year-old woman who had undergone pelvic lymphangioma resection two months previously presented with cough and dyspnea. Transthoracic echocardiography and CT demonstrated the presence of a mixed cystic/solid component tumor involving the inferior vena cava, heart and pulmonary artery. Complete resection of the cardiac tumor was performed and lymphangioma was confirmed based on histopathologic examination. To the best of our knowledge, this is the first report of lymphangiomatosis with cardiac and pelvic involvement in the published clinical literature.

  10. Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

    Directory of Open Access Journals (Sweden)

    M. Rizzo

    2011-09-01

    Full Text Available Objective: Pulmonary arterial hypertension (PAH is a rare but severe complication of connective tissue diseases (CTD, with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases, SLE (2 cases, mixed connective tissue disease (1 case and polymyositis (1 case attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

  11. An advanced protocol-driven transition from parenteral prostanoids to inhaled trepostinil in pulmonary arterial hypertension

    OpenAIRE

    Oudiz, Ronald; Agarwal, Manyoo; Rischard, Franz; De Marco, Teresa

    2016-01-01

    Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids—such as catheter-related infections and intolerable adverse effects—may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients...

  12. Facilitation of granulocyte migration into bovine pulmonary artery intimal explants by intact viable endothelium.

    OpenAIRE

    Niedermeyer, M E; Meyrick, B.; Parl, F.F.; Brigham, K L

    1984-01-01

    To characterize the role of normal endothelium in granulocyte chemotaxis, the authors measured granulocyte adherence to and migration into bovine pulmonary artery intimal explants. Explants were placed, endothelium uppermost, in chemotaxis chambers with zymosan-activated plasma in the lower well and 5 X 10(6)/ml 51Cr-labeled granulocytes in the upper well. After 15, 30, 60, 120, 180, or 240 minutes incubation at 37 C, granulocyte adherence was measured by removal of adherent granulocytes from...

  13. Transcatheter Arterial Embolization With Spherical Embolic Agent for Pulmonary Metastases From Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Akihiko, E-mail: sekia@igtc.jp; Hori, Shinichi, E-mail: horishin@igtc.jp; Sueyoshi, Satoru, E-mail: sueyoshis@igtc.jp; Hori, Atsushi, E-mail: horiat@igtc.jp; Kono, Michihiko, E-mail: konom@igtc.jp; Murata, Shinichi, E-mail: muratas@igtc.jp; Maeda, Masahiko, E-mail: maedam@igtc.jp [Gate Tower Institute for Image Guided Therapy, Department of Radiology (Japan)

    2013-12-15

    Purpose: This retrospective study aimed to evaluate the safety and local efficacy of transcatheter arterial embolization (TAE) with superabsorbent polymer microspheres (SAP-MS) in patients with pulmonary metastases from renal cell carcinoma (RCC). Methods: Sixteen patients with unresectable pulmonary metastases from RCC refractory to standard therapy were enrolled to undergo TAE with the purpose of mass reduction and/or palliation. The prepared SAP-MS swell to approximately two times larger than their dry-state size (100-150 {mu}m [n = 14], 50-100 {mu}m [n = 2]). Forty-nine pulmonary nodules (lung n = 22, mediastinal lymph node n = 17, and hilar lymph node n = 10) were selected as target lesions for evaluation. Local tumor response was evaluated 3 months after TAE according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The relationship between tumor enhancement ratio by CT during selective angiography and local tumor response was evaluated. Results: The number of TAE sessions per patient ranged from 1 to 5 (median 2.9). Embolized arteries at initial TAE were bronchial arteries in 14 patients (87.5 %) and nonbronchial systemic arteries in 11 patients (68.8 %). Nodule-based evaluation showed that 5 (10.2 %) nodules had complete response, 17 (34.7 %) had partial response, 15 (30.6 %) had stable disease, and 12 (24.5 %) had progressive disease. The response rate was significantly greater in 22 lesions that had a high tumor enhancement ratio than in 27 lesions that had a slight or moderate ratio (90.9 vs. 7.4 %, p = 0.01). Severe TAE-related adverse events did not occur. Conclusion: TAE with SAP-MS might be a well-tolerated and locally efficacious palliative option for patients with pulmonary metastases from RCC.

  14. Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology.

    Science.gov (United States)

    Morchi, Gira S; Ivy, D Dunbar; Duster, Mark C; Claussen, Lori; Chan, Kak-Chen; Kay, Joseph

    2009-04-01

    OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. DESIGN: A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t-tests were used for statistical analyses. PATIENTS: Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m(2) prior to starting sildenafil. RESULTS: Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre-treatment vs. 91.0 ± 5.5% post-treatment, P = .017). In the four out of five patients who have had follow-up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre-treatment vs. 13.8 ± 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular resistance pre- and post-sildenafil treatment (3.5 ± 1.0 Wood units × m(2) pre-treatment vs. 2.0 ± 0.4 Wood units × m(2) post-treatment, P = .031). CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.

  15. Effect of acute arteriolar vasodilation on capacitance and resistance in pulmonary arterial hypertension.

    Science.gov (United States)

    Newman, John H; Brittain, Evan L; Robbins, Ivan M; Hemnes, Anna R

    2015-04-01

    Pulmonary vascular capacitance (PVC) is reduced in pulmonary arterial hypertension (PAH). In normal lung, PVC is largely a function of vascular compliance. In PAH, increased pulmonary vascular resistance (PVR) arises from the arterioles. PVR and PVC share pressure and volume variables. The dependency between the two qualities of the vascular bed is unclear in a state of intense vasoconstriction. We compared PVC and PVR before and during nitric oxide (NO) inhalation during right-sided heart catheterization in eight NO-responsive patients with PAH. NO only directly affects tone in parenchymal vessels. During NO inhalation, pulmonary arterial systolic pressure decreased, 80 ± 20 SD to 48 ± 20 mm Hg, and stroke volume increased, 62 ± 19 mL to 86 ± 24 mL (P Wood units to 4.7 ± 2.2 Wood units (P < .012), and PVC increased from 1.4 ± 1.1 mL/mm Hg to 3.2 ± 1.8 mL/mm Hg (P < .018). The magnitude of PVR drop was 57% ± 6% and the decrease in 1/PVC was 54% ± 14% (P = not significant). In vasoresponsive PAH, PVC is a function of the pressure response of the vasoconstricted arterioles to stroke volume. Immediately upon vasodilation, the capacitance increases markedly. The compliance vessels are, thus, the same as the resistance vessels. The immediate reduction in pulmonary arterial pressure during NO inhalation suggests that large vessel remodeling is not a major contributor to systolic pressure in these patients.

  16. Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial dysfunction of pulmonary arteries in rats.

    Directory of Open Access Journals (Sweden)

    Zhuo Wang

    Full Text Available Obstructive sleep apnoea (OSA is a risk factor for cardiovascular disorders and in some cases is complication of pulmonary hypertension. We simulated OSA by exposing rats to cyclic intermittent hypoxia (CIH to investigate its effect on pulmonary vascular endothelial dysfunction. Sprague-Dawley Rats were exposed to CIH (FiO2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/wk for 3 wk, and the pulmonary arteries of normoxia and CIH treated rats were analyzed for expression of endothelin-1 (ET-1 and ET receptors by histological, immunohistochemical, RT-PCR and Western Blot analyses, as well as for contractility in response to ET-1. In the pulmonary arteries, ET-1 expression was increased, and ET-1 more potently elicited constriction of the pulmonary artery in CIH rats than in normoxic rats. Exposure to CIH induced marked endothelial cell damage associated with a functional decrease of endothelium-dependent vasodilatation in the pulmonary artery. Compared with normoxic rats, ETA receptor expression was increased in smooth muscle cells of the CIH rats, while the expression of ETB receptors was decreased in endothelial cells. These results demonstrated endothelium-dependent vasodilation was impaired and the vasoconstrictor responsiveness increased by CIH. The increased responsiveness to ET-1 induced by intermittent hypoxia in pulmonary arteries of rats was due to increased expression of ETA receptors predominantly, meanwhile, decreased expression of ETB receptors in the endothelium may also participate in it.

  17. An excellent result of surgical treatment in patients with severe pulmonary arterial hypertension following mitral valve disease.

    Science.gov (United States)

    Song, Xiaochun; Zhang, Cui; Chen, Xin; Chen, Yongming; Shi, Qiankun; Niu, Yongsheng; Xiao, Jilai; Mu, Xinwei

    2015-05-13

    Observe the efficacy of surgical treatment in patients with severe pulmonary arterial hypertension caused by mitral valve disease. We examined the results of surgical treatment in 32 patients with mitral valve disease and severe pulmonary arterial hypertension (pulmonary arterial systolic pressure ≥ 80 mmHg) retrospectively. Operative and postoperative data collection included type of the surgery, cardiopulmonary bypass time, cross-clamp time and the mortality rate. Pulmonary arterial systolic pressure, left atrial diameter, left ventricular end-diastolic diameter, and left ventricular ejection fraction were recorded and compared. A total number of 32 patients had the operation of mitral valve replacement. Among those subjects, twenty-seven patients were surgically replaced with mechanical prosthesis and five patients with tissue prosthesis. Only one patient died of pneumonia, with a mortality rate of 3.1 %. The statistical results of preoperative and postoperative echocardiographic data showed significant decrease in pulmonary arterial systolic pressure (101.2 ± 20.3 versus 48.1 ± 14.3 mmHg, P Mitral valve replacement can be performed successfully in patients with mitral valve disease and severe pulmonary arterial hypertension with an acceptable perioperative risk.

  18. Endovascular Treatment of an Aneurysmal Aberrant Systemic Artery Supplying a Pulmonary Sequestrum

    Energy Technology Data Exchange (ETDEWEB)

    Kristensen, Katrine Lawaetz, E-mail: klk@dadlnet.dk [Odense University Hospital, Department of Thoracic and Vascular Surgery (Denmark); Duus, Louise Aarup, E-mail: louise.brodersen@gmail.com [Sygehus Lillebaelt Vejle, Department of Radiology (Denmark); Elle, Bo, E-mail: Bo.Elle@rsyd.dk [Odense University Hospital, Department of Radiology (Denmark)

    2015-10-15

    An aberrant systemic artery originating from the abdominal aorta supplying a pulmonary sequestration is a rare congenital malformation. This causes a left-to-left shunt. Symptoms include recurrent pneumonias, hemoptysis, and, in the long term, heart failure. Aneurysm of the aberrant vessel is rarely seen. Traditionally, treatment of pulmonary sequestrations includes ligation of the feeding vessel and lobectomy. A new promising treatment is an endovascular approach. Only a few cases describe endovascular treatment of pulmonary sequestration. This is the first published case of a giant aneurysmal branch from the abdominal aorta to the normal basal segments of the lung, successfully occluded with an Amplatzer Vascular Plug II (AVP II, St.Jude Medical, MN, USA) alone.

  19. Transient but not genetic loss of miR-451 is protective in the development of pulmonary arterial hypertension

    NARCIS (Netherlands)

    Grant, Jennifer S; Morecroft, Ian; Dempsie, Yvonne; van Rooij, Eva; MacLean, Margaret R; Baker, Andrew H

    2013-01-01

    MicroRNAs are small noncoding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work has established that miR-451 is upregulated in rodent models of PAH. The role of miR-451 in the pulmonary

  20. Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

    NARCIS (Netherlands)

    Szulcek, R.; Happe, C.M.; Rol, N.; Fontijn, R.D.; Dickhoff, C.; Hartemink, K.J.; Grünberg, K.; Tu, L.; Timens, W.; Nossent, G.D.; Paul, M.A.; Leyen, T.A.; Horrevoets, A.J.; Man, F.S. de; Guignabert, C.; Yu, P.B.; Vonk-Noordegraaf, A.; Nieuw Amerongen, G.P. van; Bogaard, H.J.

    2016-01-01

    RATIONALE: Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear. OBJECTIVES: We hypothesize that

  1. Prevalence of renal artery stenosis in flash pulmonary oedema: determination using gadolinium-enhanced MRA.

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    PURPOSE: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS. MATERIALS AND METHODS: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension\\/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+\\/-SD). RESULTS: 20 patients (4 male, 16 female, age 78.5+\\/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+\\/-38 mm Hg) than those without (134+\\/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+\\/-23 mm Hg) than those without (76+\\/-17 mm Hg) (p<.01). All patients with RAS and 6\\/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed. CONCLUSION: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation.

  2. Intra-procedural Bronchoscopy to Prevent Bronchial Compression During Pulmonary Artery Stent Angioplasty.

    Science.gov (United States)

    O'Byrne, Michael L; Rome, Nita; Santamaria, Ramiro W Lizano; Hallbergson, Anna; Glatz, Andrew C; Dori, Yoav; Gillespie, Matthew J; Goldfarb, Samuel; Haas, Andrew R; Rome, Jonathan J

    2016-03-01

    Stenosis of the pulmonary arteries frequently occurs during staged palliation of hypoplastic left heart syndrome and variants, often necessitating stent angioplasty. A complication of stent angioplasty is compression of the ipsilateral mainstem bronchus. Following such a case, we re-evaluated our approach to PA stent angioplasty in these patients. The incident case is described. A retrospective observational study of children and adults with superior (SCPC) and/or total cavopulmonary connection (TCPC) undergoing left pulmonary artery (LPA) stent angioplasty between January 1, 2005 and January 5, 2014 and subsequent chest CT was performed to assess the incidence of bronchial compression. The current strategy of employing bronchoscopy to assess bronchial compression during angioplasty is described with short-term results. Sixty-five children and adults underwent LPA stent angioplasty. Other than the incident case, none had symptomatic bronchial compression. Of the total study population, 12 % had subsequent CT, of which one subject had moderate bronchial compression. To date, seven subjects have undergone angioplasty of LPA stenosis and bronchoscopy. In one case, stent angioplasty was not performed because of baseline bronchial compression, exacerbated during angioplasty. In the rest of cases, mild-moderate compression was seen during angioplasty. Following stent angioplasty, the resultant compression was not worse than that seen on test angioplasty. Bronchial compression is a rare complication of stent angioplasty of the pulmonary arteries in children and adults with SCPC/TCPC. Angioplasty of the region of interest with procedural bronchoscopy can help to identify patients at risk of this complication.

  3. Acute absolute vasodilatation is associated with a lower vascular wall stiffness in pulmonary arterial hypertension.

    Science.gov (United States)

    Grignola, Juan C; Domingo, Enric; Aguilar, Rio; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Roman, Antonio

    2013-04-05

    Acute vasoreactivity testing (VT) is considered mandatory in the diagnostic work-up of patients with pulmonary arterial hypertension (PAH). We studied the relation between the acute absolute arterial vasodilatation and the severity of vascular remodeling estimated by intravascular ultrasound (IVUS) in patients with idiopathic PAH. Simultaneous right heart catheterization and IVUS of the pulmonary artery (PA) were performed both in basal conditions and during short-term intravenous epoprostenol infusion in nineteen idiopathic PAH patients. Pulmonary vascular resistance (PVRi) and capacitance indexes (stroke volume/pulse pressure, Cp), were calculated. Local pulsatility was estimated by IVUS (IVUSp) (systolic-diastolic lumen area/diastolic lumen area×100; sA-dA/dA) and PA stiffness was assessed by the elastic modulus (E: pulse pressure/IVUSp). Epoprostenol infusion (11±2ng/kg/min) determined a real vasodilatation (increment of dA>10%) in six patients. This vasodilation group presented on average significantly higher cardiac index, stroke volume index and Cp, and lower PVRi and IVUSp (Prights reserved.

  4. Gerbode defect following endocarditis and misinterpreted as severe pulmonary arterial hypertension

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    Allajbeu Iris

    2010-09-01

    Full Text Available Abstract A Gerbode -type defect is a ventricular septal defect communicating directly between the left ventricle and right atrium. It is usually congenital, but rarely is acquired, as a complication of endocarditis. This can be anatomically possible because the normal tricuspid valve is more apically displaced than the mitral valve. However, identification of an actual communication is often extremely difficult, so a careful and meticulous echocardiogram should be done in order to prevent echocardiographic misinterpretation of this defect as pulmonary arterial hypertension. The large systolic pressure gradient between the left ventricle and the right atrium would expectedly result in a high velocity systolic Doppler flow signal in right atrium and it can be sometimes mistakably diagnosed as tricuspid regurgitant jet simulating pulmonary arterial hypertension. We present a rare case of young woman, with endocarditis who presented with severe pulmonary arterial hypertension. The preoperative diagnosis of left ventricle to right atrial communication (acquired Gerbode defect was suspected initially by echocardiogram and confirmed at the time of the surgery. A point of interest, apart from the diagnostic problem, was the explanation for its mechanism and presentation. The probability of a bacterial etiology of the defect is high in this case.

  5. Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Palevsky Harold I

    2005-04-01

    Full Text Available Abstract Background The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. Methods 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. Results For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each. Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09. All telephone tests were completed within one hour. Conclusion Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

  6. Endothelial hyperpermeability in severe pulmonary arterial hypertension: role of store-operated calcium entry

    Science.gov (United States)

    Zhou, Chun; Townsley, Mary I.; Alexeyev, Mikhail; Voelkel, Norbert F.

    2016-01-01

    Here, we tested the hypothesis that animals with severe pulmonary arterial hypertension (PAH) display increased sensitivity to vascular permeability induced by activation of store-operated calcium entry. To test this hypothesis, wild-type and transient receptor potential channel 4 (TRPC4) knockout Fischer 344 rats were given a single injection of Semaxanib (SU5416; 20 mg/kg) followed by 3 wk of exposure to hypoxia (10% oxygen) and a return to normoxia (21% oxygen) for an additional 2–3 wk. This Semaxanib/hypoxia/normoxia (i.e., SU5416/hypoxia/normoxia) treatment caused PAH, as evidenced by development of right ventricular hypertrophy, pulmonary artery medial hypertrophy, and occlusive lesions within precapillary arterioles. Pulmonary artery pressure was increased fivefold in Semaxanib/hypoxia/normoxia-treated animals compared with untreated, Semaxanib-treated, and hypoxia-treated controls, determined by isolated perfused lung studies. Thapsigargin induced a dose-dependent increase in permeability that was dependent on TRPC4 in the normotensive perfused lung. This increase in permeability was accentuated in PAH lungs but not in Semaxanib- or hypoxia-treated lungs. Fluid accumulated in large perivascular cuffs, and although alveolar fluid accumulation was not seen in histological sections, Evans blue dye conjugated to albumin was present in bronchoalveolar lavage fluid of hypertensive but not normotensive lungs. Thus PAH is accompanied by a TRPC4-dependent increase in the sensitivity to edemagenic agents that activate store-operated calcium entry. PMID:27422996

  7. Gerbode defect following endocarditis and misinterpreted as severe pulmonary arterial hypertension.

    Science.gov (United States)

    Xhabija, Nereida; Prifti, Edvin; Allajbeu, Iris; Sula, Fatmir

    2010-09-30

    A Gerbode-type defect is a ventricular septal defect communicating directly between the left ventricle and right atrium. It is usually congenital, but rarely is acquired, as a complication of endocarditis. This can be anatomically possible because the normal tricuspid valve is more apically displaced than the mitral valve. However, identification of an actual communication is often extremely difficult, so a careful and meticulous echocardiogram should be done in order to prevent echocardiographic misinterpretation of this defect as pulmonary arterial hypertension. The large systolic pressure gradient between the left ventricle and the right atrium would expectedly result in a high velocity systolic Doppler flow signal in right atrium and it can be sometimes mistakably diagnosed as tricuspid regurgitant jet simulating pulmonary arterial hypertension. We present a rare case of young woman, with endocarditis who presented with severe pulmonary arterial hypertension. The preoperative diagnosis of left ventricle to right atrial communication (acquired Gerbode defect) was suspected initially by echocardiogram and confirmed at the time of the surgery. A point of interest, apart from the diagnostic problem, was the explanation for its mechanism and presentation. The probability of a bacterial etiology of the defect is high in this case.

  8. In vivo assessment of pulmonary arterial wall fibrosis by intravascular optical coherence tomography in pulmonary arterial hypertension: a new prognostic marker of adverse clinical follow-up.

    Science.gov (United States)

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Montero, María Angeles; Arredondo, Christian; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Bouteldja, Nadia; Hidalgo, Cristina; Roman, Antonio

    2013-01-01

    The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm(2), % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome.

  9. [Pulmonary arterial hypertension--experience of Centro Hospitalar de Vila Nova de Gaia].

    Science.gov (United States)

    Oliveira, Ana; Ferreira, Daniela; Caiado, António; Ferreira, Susana; Ferreira, Paula; Santos, Lino; Gonçalves, Manuel; Shiang, Teresa

    2007-01-01

    Pulmonary arterial hypertension (PAH) is a serious and progressive disease, potentially fatal in a few years. Until the 1990s the only effective treatment for this disease was pulmonary/cardiopulmonary transplant. Over the last few years several drugs have emerged that have modified the course of the disease. To characterise patients with PAH followed at Centro Hospitalar de V.N.Gaia between 2000 and 2006. To raise awareness of this entity. Retrospective analysis of all patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) followed at our Hospital. In this period 11 patients were observed, 7 women and 4 men, with a mean age of 43 y. Five patients had idiopathic PAH, three had CTEPH, two had PAH associated with interauricular communication and one had PAH associated with CREST Syndrome. At the time of diagnosis most patients were in NYHA/ /WHO Functional Class III/IV, mean systolic pulmonary artery pressure was 98+/-32 mm Hg and mean distance walked in the 6-minute walk test was 401 m. Initial treatment: Three patients had inhaled iloprost, two subcutaneous treprostinil, three oral bosentan, one oral sildenafil and two patients under- went surgery. Mean follow-up time was 28.1 months. Five patients recovered, three are stable, one worsened and two died. PAH is a serious illness which requires a multidisciplinary approach with the need for complex and expensive therapies. Diagnosis in initial sta- ges is essential for an effective treatment.

  10. Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements

    Energy Technology Data Exchange (ETDEWEB)

    Alunni, Jean-Philippe; Otal, Philippe; Rousseau, Herve; Chabbert, Valerie [CHU Rangueil, Department of Radiology, Toulouse (France); Degano, Bruno; Tetu, Laurent; Didier, Alain [CHU Larrey, Department of Pneumology, Toulouse (France); Arnaud, Catherine [CHU Rangueil, Department of Methods in Clinical Research, Toulouse (France); Blot-Souletie, Nathalie [CHU Rangueil, Department of Cardiology, Toulouse (France)

    2010-05-15

    To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. Cardiac MRI can help to assess the severity of PH. (orig.)

  11. Tyrosine kinase inhibitors in pulmonary arterial hypertension: a double-edge sword?

    Science.gov (United States)

    Godinas, Laurent; Guignabert, Christophe; Seferian, Andrei; Perros, Frederic; Bergot, Emmanuel; Sibille, Yves; Humbert, Marc; Montani, David

    2013-10-01

    New treatments for pulmonary arterial hypertension (PAH) are a crucial need. The increased proliferation, migration, and survival of pulmonary vascular cells within the pulmonary artery wall in PAH have allowed successful transposition of pathophysiological elements from oncologic researches. Next steps will require translation of these biological advances in PAH therapeutic arsenal and guidelines. This review synthesizes recent data concerning the role of receptor tyrosine kinases and their inhibitors in PAH, with implications in animal models and humans. Results of clinical trials are now accumulating to establish beneficial role of tyrosine kinase inhibitors (TKIs) in PAH and further findings are expected in the near future. Beside this curative approach, evidences of a possible TKI-induced cardiotoxicity are emerging. These safety issues raise concern about a potential amplified harmful effect in PAH, a pathology characterized by an underlying cardiac dysfunction. In addition, analyses of PAH registries shed light on a selective pulmonary vascular toxicity triggered by TKIs, especially dasatinib. These possible dual effects of the TKIs in PAH need to be taken in account for future pharmacological development of this therapeutic class in PAH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Effects of chronic intermittent asphyxia on haematocrit, pulmonary arterial pressure and skeletal muscle structure in rats.

    Science.gov (United States)

    Bradford, Aidan

    2004-01-01

    Sleep-disordered breathing in humans is a common condition associated with serious cardiovascular and other abnormalities. The prevalence and pathogenesis of increased haematocrit and pulmonary hypertension is controversial and it has been suggested that these changes only occur in patients who also have daytime continuous hypoxaemia. The hypothesis tested here is that the chronic intermittent hypoxia and asphyxia associated with sleep-disordered breathing causes erythropoiesis and pulmonary hypertension and that this occurs in the absence of periods of continuous hypoxia. In humans and animals with obstructive sleep apnoea, there are abnormalities of upper airway muscle structure that have been ascribed to increased load placed on these muscles. An alternative hypothesis is that chronic intermittent hypoxia and asphyxia cause changes in upper airway muscle structure and function. To test these hypotheses, rats were exposed to intermittent hypoxia and asphyxia for 8 h per day for 5 weeks. This caused an increase in haematocrit, right ventricular weight and pulmonary arterial pressure. There were only slight changes in diaphragm, upper airway and limb muscle structure and force production but in general, muscle fatigability was increased. In conclusion chronic intermittent hypoxia and asphyxia cause an increase in haematocrit and pulmonary arterial pressure in the absence of periods of continuous hypoxia. Chronic intermittent hypoxia and asphyxia have little effect on skeletal muscle structure and force production but increase muscle fatigue. Increased upper airway muscle fatigue could lead to a vicious cycle of further compromise in upper airway patency and further hypoxia and asphyxia.

  13. Severe Pulmonary Arterial Hypertension Induced by SU5416 and Ovalbumin Immunization

    Science.gov (United States)

    Mizuno, Shiro; Farkas, Laszlo; Al Husseini, Aysar; Farkas, Daniela; Gomez-Arroyo, Jose; Kraskauskas, Donatas; Nicolls, Mark R.; Cool, Carlyne D.; Bogaard, Herman J.

    2012-01-01

    The combination of chronic hypoxia and treatment of rats with the vascular endothelial growth factor (VEGF) receptor blocker, SU5416, induces pulmonary angio-obliteration, resulting in severe pulmonary arterial hypertension (PAH). Inflammation is thought to contribute to the pathology of PAH. Allergic inflammation caused by ovalbumin (OVA) immunization causes muscularization of pulmonary arteries, but not severe PAH. Whether disturbance of the immune system and allergic inflammation in the setting of lung endothelial cell apoptosis causes PAH is unknown. We investigated the effects of OVA-allergic inflammation on the development of PAH initiated by VEGF blockade–induced lung endothelial cell apoptosis. OVA-immunized rats were treated with SU5416 to induce pulmonary vascular endothelial cell apoptosis. The combination of OVA and SU5416 treatment resulted in severe angio-obilterative PAH, accompanied by increased IL-6 expression in the lungs. c-Kit+ and Sca-1+ cells were found in and around the lung vascular lesions. Pan-caspase inhibiton, dexamethasone treatment, and depletion of B-lymphocytes using an anti-CD20 antibody suppressed this remodeling. OVA immunization also increased lung tissue hypoxia-induced factor-1α and VEGF expression. Our results also suggest that the increased expression of hypoxia-induced factor-1α and IL-6 induced by the allergic lung inflammation may be a component of the pathogenesis of PAH. PMID:22842496

  14. The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Jeremy A Falk

    2010-04-01

    Full Text Available Jeremy A Falk, Kiran J Philip, Ernst R SchwarzCedars Sinai Women’s Guild Lung Institute, Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USAAbstract: Pulmonary hypertension (PH is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH. Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5 inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.Keywords: PDE-5 inhibition, pulmonary hypertension, tadalafil

  15. Late presentation of an anomalous left coronary artery from the pulmonary artery treated with conservative surgical management with long-term cardiac magnetic resonance imaging follow-up

    Directory of Open Access Journals (Sweden)

    Pishoy Gouda

    2017-02-01

    Full Text Available Anomalous origin of the left coronary artery from the pulmonary artery is rare congenital abnormality that most commonly presents in childhood and is associated with a high mortality. In the elderly, patients may present acutely with arrhythmias or signs of ischemia or with vague chronic presentations of shortness of breath and fatigue. In the high-risk elderly population, it is unclear as to whether conservative surgical management by means of suture ligation of the left coronary artery is associated with positive long-term outcomes. We present a case of a 69-year-old patient diagnosed with anomalous origin of the left coronary artery from the pulmonary artery, which was treated with conservative surgical management and followed up for 15 years with cardiovascular magnetic resonance imaging, with positive outcomes.

  16. The effects of mycophenolate mofetil on cytokines and their receptors in pulmonary arterial hypertension in rats.

    Science.gov (United States)

    Zhang, Y F; Zheng, Y

    2015-01-01

    To analyse the effects of mycophenolate mofetil (MMF) on pulmonary artery pressure (PAP) and the expression of cytokines and their receptors in a rat model of pulmonary arterial hypertension (PAH). Thirty-eight healthy male inbred Sprague-Dawley rats were divided randomly into four groups: a control group, a monocrotaline (MCT) group, an MMF20 group (MCT+20 mg/kg/day MMF), and an MMF40 group (MCT+40 mg/kg/day MMF). Systolic PAP (SPAP), the right ventricular hypertrophy index (RVI), and the levels of expression of cytokines and their receptors were measured and analysed. SPAP, RVI, levels of expression of basic fibroblast growth factor (bFGF) in serum and lung homogenates, alveolar arterial wall thickness, and the number of muscular arteries in the MMF20 and MMF40 groups were decreased in comparison with the MCT group. MMF inhibits the formation of vascular muscle and decreases SPAP and RVI by inhibition of the expression of bFGF, endothelin-1 (ET-1), and their receptors, resulting in the inhibition of smooth muscle proliferation and amelioration of PAH.

  17. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Fukuda, Yutaka; Momoi, Nobuo; Akaihata, Mitsuko; Nagasawa, Katsutoshi; Mitomo, Masaki; Aoyagi, Yoshimichi; Endoh, Kisei; Hosoya, Mitsuaki

    2015-08-01

    Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists. © 2015 Japan Pediatric Society.

  18. Peripheral arterial disease: an underestimated aetiology of exercise intolerance in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Castagna, Olivier; Boussuges, Alain; Nussbaum, Eric; Marqueste, Louis; Brisswalter, Jeanick

    2008-06-01

    To assess the prevalence of peripheral arterial disease and its implications for exercise limitation in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-one moderate-to-severe COPD patients (forced expiratory volume in 1 s: 37+/-6 SD% predicted) and 73 healthy age-matched control individuals (divided into 31 smokers and 42 nonsmokers) participated in this study. All COPD patients were either exsmokers or current smokers and their tobacco-smoking history was similar to that of healthy smokers. To evaluate the existence of arterial disease, lower limb perfusion pressure impairment was assessed using the ankle brachial index, whereas arterial stiffness was assessed by the pulse wave velocity (PWV). The definition of peripheral arterial disease required an ankle brachial index value of 0.90 or less, whereas the PWV increment was considered to be a direct witness of arterial stiffness increase. A 6-min walk test was performed to assess physical exercise capacity. Prevalence of peripheral arterial disease was higher in COPD patients than in healthy participants (81+/-3 SD; 49+/-5 SD and 9+/-2 SD%, respectively, in COPD, healthy smokers and nonsmokers). PWV mean values were significantly higher in COPD patients compared with healthy smokers and nonsmokers (10.3+/-2.1 SD m/s; 9.2+/-1.3 SD m/s and 8.7+/-2.2 SD m/s, respectively). The distance covered during the 6-min-walk test was associated positively with the degree of peripheral arterial disease (r=0.78; P=0.05) and negatively with the PWV values (r=-0.74; P=0.05). Not only tobacco-smoking history but also COPD severity was shown to influence these associations. The effect of peripheral arterial disease on exercise intolerance in COPD seems to be considerable. Therefore, COPD patients participating in a pulmonary rehabilitation programme should profit from a systematic search for arterial disease. Arterial dysfunction has to be taken into account in the multidisciplinary treatment of these

  19. Energy efficiency and pulmonary artery flow after balloon pulmonary angioplasty for inoperable, chronic thromboembolic pulmonary hypertension: Analysis by phase-contrast MRI.

    Science.gov (United States)

    Nagao, Michinobu; Yamasaki, Yuzo; Abe, Kohtaro; Hosokawa, Kazuya; Kawanami, Satoshi; Kamitani, Takeshi; Yamanouchi, Torahiko; Yabuuchi, Hidetake; Fukushima, Kenji; Honda, Hiroshi

    2017-02-01

    The aims of this study were to propose a new quantitative method for pulmonary artery (PA) flow energetics using phase-contrast magnetic resonance imaging (PC-MRI), and to investigate how balloon pulmonary angioplasty (BPA) impacts energetics in chronic thromboembolic pulmonary hypertension (CTEPH). PC-MRI at 3-Teslar and with a flow sensitive gradient echo was used to examine energetics prior to and following BPA for 24 CTEPH patients. Stroke volume (m; ml) and mean velocity (V; mm/s) for the main pulmonary artery (PA), right PA, and left PA were calculated from a time-flow curve derived from PC-MRI. Based on the Bernoulli principle, PA energy was identified as 1/2mV 2 (μj/kg), and energy loss was defined as the following equation "energy loss=main PA energy-(rt. PA energy+lt. PA energy)". Right PA energy was significantly greater post-BPA than pre-BPA (61±55 vs. 32±40μj/kg). There was no difference in main PA and left PA energies. Energy loss was significantly decreased post-BPA (18±97μj/kg) than pre-BPA (79±125μj/kg). An optimal cutoff of left PA energy of 45μj/kg pre-BPA can be used to predict patients with mPAP≥30mmHg after BPA, with an area under the curve of 0.91, 78% sensitivity, and 92% specificity. Analysis of PA energetics using phase-contrast MRI demonstrates that BPA improves energy loss in CTEPH. In addition, BPA responses can be predicted by PA energy status pre-treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Pulmonary Arterial Lesions in New World Camelids in Association With Dicrocoelium dendriticum and Fasciola hepatica Infection.

    Science.gov (United States)

    Hilbe, M; Robert, N; Pospischil, A; Gerspach, C

    2015-11-01

    In Switzerland, dicrocoeliasis is regarded as the most significant parasitic infection of llamas and alpacas. Fasciola hepatica infestation is also a problem but less common. The aim of the present retrospective study was to evaluate the lungs of New World camelids (NWCs) for evidence of arterial hypertension in association with liver changes due to liver fluke infestation. The lungs of 20 llamas and 20 alpacas with liver fluke infestation were histologically evaluated. The hematoxylin and eosin and van Gieson (VG)-elastica stains as well as immunohistology for the expression of α-smooth muscle actin (α-SMA) were used to visualize the structures of arterial walls. Parasitology of fecal matter (11 llamas and 17 alpacas) confirmed that most of these animals were infested with both Dicrocoelium dendriticum and other gastrointestinal parasites. In most cases (10/12 llamas, 4/6 alpacas), liver enzyme activity in serum was elevated. Histologically, arteries in the lungs of 9 of 20 llamas (45%) and 3 of 20 alpacas (15%) showed severe intimal and adventitial and slight to moderate medial thickening, which was confirmed with α-SMA and VG-elastica staining. All animals exhibited typical liver changes, such as fibrosis and biliary hyperplasia, in association with the presence of liver flukes. This study shows that liver flukes can induce proliferative changes in lung arteries in NWCs that resemble those seen with pulmonary arterial hypertension due to liver parasites in humans. However, the degree of liver fluke infestation was not correlated with the extent of liver damage, or with the amount of thoracic or abdominal effusion or pulmonary arterial changes. © The Author(s) 2015.

  1. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    Science.gov (United States)

    Cheung, A K; Parker, C J; Wilcox, L

    1989-11-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement.

  2. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    Science.gov (United States)

    Cheung, A K; Parker, C J; Wilcox, L

    1989-01-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement. PMID:12412765

  3. Experimental model for creation of carotid artery aneurysms in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hyun; Han, Moon Hee; Yu, In Kyu; Lee, Sang Hyun; Chang, Kee Hyun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-11-01

    To describe the detailed technique for producing experimental carotid aneurysms in dogs and the success rate, cause of failure and remedy, based on our experience. Fourteen male dogs weighing 12-15kg were anesthetized with inhalation of 1-2% halothane and 50% nitrous oxide. Each surgical procedure was performed under sterile condition with the aid of an operating microscope. A paramidline incision 7-8cm in length was made parallel to and medial to the external jugular vein in the dog's neck. The external jugular vein was harvested as a 1cm vein pouch by ligation and division of the proximal and distal ends. The ipsilateral common carotid artery was exposed and clamped at both ends by a vascular clamp. A 5-mm long elliptical arteriotomy was made at the mid portion of the artery, and then end to side anastomosis between the artery and vein sac was performed by using interrupted 7-0 monofilament prolene sutures. Carotid arteriography or Doppler sonography was performed 1-6 weeks after aneurysm construction. Twenty experimental aneurysms were constructed, and 17 aneurysms were patent on follow up study, but one dog with two aneurysms died from hemorrhagic pneumonia 17 days after surgery. The overall patency rate was 75%. We demonstrated the feasibility of creating experimental aneurysm models in the dog and expect that the technique presented will help to avoid failure in the construction of aneurysms.

  4. PDGF-BB/KLF4/VEGF Signaling Axis in Pulmonary Artery Endothelial Cell Angiogenesis.

    Science.gov (United States)

    Liang, Songhe; Yu, Hao; Chen, Xinxin; Shen, Tingting; Cui, Zhongqi; Si, Genle; Zhang, JunTing; Cheng, Yue; Jia, Shiwei; Song, Shasha; Zhang, Xiang; Yu, Xiufeng

    2017-01-01

    Accumulating evidence suggests that platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor(VEGF) play a role in the progression of pulmonary arterial hypertension (PAH).Since chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary arteries, which are histological hallmarks of PAH, we explored the role of the PDGF-BB/KLF4/VEGF signaling axis in the angiogenesis of pulmonary artery endothelial cells (PAECs). Adult male Wistar rats were used to study hypoxia-induced or monocrotaline (MCT)-induced right ventricular (RV) remodeling as well as systolic function and hemodynamics using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV vessels were performed. The results revealed that both the PDGF receptor-tyrosine kinase inhibitor imatinib and the multi-targeted VEGF and PDGF receptor inhibit or sunitinib malate reversed hypoxia-induced increases in right ventricular systolic pressure (RVSP), right ventricular function and thickening of the medial walls. Mechanistically VEGF/VEGFR and PDGF/PDGFR formed a biological complex. We also showed that PDGF-BBincreasedKLF4 promoter activity transcriptionally activating VEGF expression, which regulates PAEC proliferation; migration; and the cell-cycle transition from G0/G1phase to S phase and G2/M-phase and eventually leads to PAEC angiogenesis Conclusion: Our study indicates that hypoxia-induced angiogenesis of PAECs is associated with increased levels of PDGF-BB/KLF4/VEGF, which contribute to pulmonary vascular remodeling. Overall, our study contributes to a better understanding of PAH pathogenesis. © 2017 The Author(s). Published by S. Karger AG, Basel.

  5. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2).

    Science.gov (United States)

    Rubin, Lewis J; Galiè, Nazzareno; Grimminger, Friedrich; Grünig, Ekkehard; Humbert, Marc; Jing, Zhi-Cheng; Keogh, Anne; Langleben, David; Fritsch, Arno; Menezes, Flavia; Davie, Neil; Ghofrani, Hossein-Ardeschir

    2015-05-01

    Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class. Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean±sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year. Copyright ©ERS 2015.

  6. Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

    Science.gov (United States)

    Bessa, Luiz Gustavo Pignataro; Junqueira, Flávia Pegado; Bandeira, Marcelo Luiz da Silva; Garcia, Marcelo Iorio; Xavier, Sérgio Salles; Lavall, Guilherme; Torres, Diego; Waetge, Daniel

    2013-01-01

    Background Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. Objective To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Methods Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. Results The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m2, and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m2, there was a relevant association with the increased percentage of myocardial fibrosis. Conclusion The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension. PMID:23979779

  7. Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bessa, Luiz Gustavo Pignataro, E-mail: lgpignataro@ig.com.br; Junqueira, Flávia Pegado; Bandeira, Marcelo Luiz da Silva; Garcia, Marcelo Iorio; Xavier, Sérgio Salles; Lavall, Guilherme; Torres, Diego; Waetge, Daniel [Hospital Universitário Clementino Fraga Filho, Ilha do Fundão, RJ (Brazil)

    2013-10-15

    Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m{sup 2}, and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m{sup 2}, there was a relevant association with the increased percentage of myocardial fibrosis. The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension.

  8. An Experimental Model of Large Pulmonary Embolism Employing Controlled Release of Subacute Caval Thrombus in Swine

    Science.gov (United States)

    Barbash, Israel M.; Schenke, William H.; Halabi, Majdi; Ratnayaka, Kanishka; Faranesh, Anthony Z.; Kocaturk, Ozgur; Lederman, Robert J.

    2011-01-01

    Purpose We aimed to develop a catheter based model of large pulmonary embolism in swine based on in situ venous thrombus formation. Materials and Methods Ten Yorkshire swine underwent transjugular implantation of a retrievable inferior vena cava (IVC) filter. A thrombin and collagen mixture was injected into a confined space created by two inflated balloons proximal and distal to the IVC filter. Animals were survived for 7±3 days to allow the thrombus to organize in situ. The caval thrombus was released upon transcatheter retrieval of the IVC filter and embolized into the main and branch pulmonary arteries. The severity of pulmonary embolism was scored by digital subtraction angiography (Miller index). At necropsy thrombi were recovered and analyzed by histopathology. Results Large pulmonary embolism was induced in all animals (average Miller index score of 15±5). Two animals developed saddle embolus with bilateral pulmonary artery occlusion and five developed proximal occlusion of either the left or right pulmonary arteries. Nevertheless no animal exhibited significant hemodynamic compromise. Large tubular thrombi were explanted in the size range of 5–10 cm long and .5–1 cm wide. Histology indicated an organized thrombus with infiltration of white blood cells and fibrin deposition. Conclusions Large caval thrombi can be formed in vivo and released at a predetermined time to induce large pulmonary embolism in a large animal model. This may help developing and testing new therapeutic approaches for pulmonary embolism. PMID:21802315

  9. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2012-01-01

    Full Text Available The use of carbon tetrachloride (CCl4 in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks, G2 (16 weeks. We found significant increase of transaminase levels and lipid peroxidation (TBARS in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-α and IL-1β in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

  10. Pulmonary artery hypertension in heart transplant recipients: how much is too much?

    Science.gov (United States)

    De Santo, Luca Salvatore; Romano, Gianpaolo; Maiello, Ciro; Buonocore, Marianna; Cefarelli, Mariano; Galdieri, Nicola; Nappi, Gianantonio; Amarelli, Cristiano

    2012-11-01

    Unresponsive pulmonary hypertension (PH) may contraindicate heart transplant since it implies poor early outcomes. The present study reports the effectiveness of oral perioperative sildenafil in allowing heart transplant candidacy and surgery in a selected group of patients initially deemed ineligible because of PH. Between May 2005 and December 2009, 31 consecutive patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a history of coronary artery disease, 10 with previous sternotomies, 71.42 ± 27.69 ml/min/m(2) mean preoperative epidermal growth factor receptor) were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility (mean pulmonary vascular resistance index: 9.57 ± 4.07 WU, mean transpulmonary gradient 14.47 ± 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96 ± 15.15 mmHg), allowing listing despite a higher risk for early post-transplant RV failure. Transplant protocol included donor/recipient size matching ≥ 0.8 and inhaled nitric oxide in the early postoperative period followed by reinstitution of oral sildenafil. All patients underwent heart transplantation. Mean overall graft ischaemic time was 179 ± 47 min; mean donor recipient weight ratio was 1.04 ± 0.17. Right ventricular failure developed in three patients (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary haemodynamic profile normalization within the third postoperative month allowing weaning from sildenafil in the 30 hospital survivors. One-year RHC confirmed PH reversal (n = 29 patients, all who survived up to 1 year). This pilot prospective uncontrolled trial suggests that oral sildenafil is effective in allowing candidacy, safe transplantation and postoperative pulmonary profile normalization in potential recipients initially disqualified because of PH.

  11. The Assessment of Right Ventricular Function and Pulmonary Artery 
Hemodynamics in Patients with Pulmonary Hypertension by 1.5T MRI

    Directory of Open Access Journals (Sweden)

    Yan HAN

    2012-08-01

    Full Text Available Background and objective Pulmonary hypertension (PH is characterized by rising pulmonary arterial pressure, decreasing right ventricular (RV function, and ultimately, RV failure. Therefore, it is important to monitor RV function and pulmonary artery hemodynamics accurately and noninvasively. This study evaluates cardiac magnetic resonance imaging (CMRI in assessing RV function and pulmonary artery hemodynamics in patients with PH. Methods Cine-MRI and phase-contrast MRI (PC-MRI were performed in 25 PH patients and 30 healthy volunteers. Cine-MRI images were post-processed on Report Card software and the following parameters were obtained: RV end-diastolic volume (EDV, end-systolic volume (ESV, stroke volume (SV, ejection fraction (EF, and myocardial mass (MM. Except for EF, all of the above parameters were normalized to body surface area (BSA. PC-MRI images were post-processed on Report Card software, peak velocity and distensibility of main pulmonary artery (MPA could also be obtained. Student t test was employed for statistical assessment.Results Compared with controls, RV EDV, ESV and MM index in PH patients were significantly increased (P<0.01, EF was significantly impaired (P<0.01, peak velocity and distensibility of MPA were significantly lower (P<0.01. SV index between the two groups had no significant difference (P>0.05. Conclusion Cardiac MRI is of great value in the assessment of RV function and MPA hemodynamic parameters in patients with PH.

  12. Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Weatherald, Jason; Boucly, Athénaïs; Chemla, Denis; Savale, Laurent; Peng, Mingkai; Jevnikar, Mitja; Jaïs, Xavier; Taniguchi, Yu; O'Connell, Caroline; Parent, Florence; Sattler, Caroline; Hervé, Philippe; Simonneau, Gérald; Montani, David; Humbert, Marc; Adir, Yochai; Sitbon, Olivier

    2018-02-13

    Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established. Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC. Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; P 440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation ( P variables that were independently

  13. Underrated value of repeated right heart catheterization in pulmonary hypertension with heart failure-a case of persisted pulmonary arterial hypertension after treatment for biventricular failure.

    Science.gov (United States)

    Park, Shinhee; Yoon, Hee Young; Jeung, Soomin; Lee, Nah Kyum; Kim, Min-Seok; Ahn, Jung-Min; Kim, Dae-Hee; Lee, Jae Seung

    2015-10-01

    Pulmonary hypertension (PH) is a common complication of left heart disease and its presence in patients with heart failure predicts worse clinical outcomes. Specific agents targeting pulmonary arterial hypertension (PAH) have been developed over the last few years, but the efficacy of these agents in pulmonary hypertension due to left heart disease (PH-LHD) is uncertain. We report a case of idiopathic pulmonary arterial hypertension (IPAH) initially presented with biventricular failure, which was misdiagnosed as PH-LHD. A 31-year-old man who had a history of recurrent hemoptysis was referred to our center with biventricular failure. Right heart catheterization (RHC) showed elevated mean pulmonary arterial pressure (mPAP) and pulmonary capillary wedge pressure (PCWP). He was diagnosed as having PH-LHD, specifically combined post-capillary and precapillary PH (CpcPH). We treated him for 2 years with diuretics, a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, and sildenafil, which was added to treat CpcPH. A follow-up echocardiography showed that biventricular function had improved, but not PH. A second RHC revealed elevated mPAP and normal PCWP, which made us change the diagnosis to IPAH. In conclusion, it is important to perform repeated RHC in CpcPH patients after the improvement of left heart dysfunction to distinguish CpcPH from IPAH.

  14. Systematic review of trials using vasodilators in pulmonary arterial hypertension: why a new approach is needed.

    Science.gov (United States)

    Macchia, Alejandro; Marchioli, Roberto; Tognoni, Gianni; Scarano, Marco; Marfisi, Rosamaria; Tavazzi, Luigi; Rich, Stuart

    2010-02-01

    In a previous meta-analysis on the approved treatments for pulmonary hypertension, we reported that all therapies caused small changes in 6-minute walk distance over a short period, with minimal effects on hemodynamics and no effect on survival. Since that last review, 10 new clinical trials with about 1,500 patients have been published, which has increased the statistical power of our observations. A systematic review of all clinical trials in pulmonary arterial hypertension was done. The pooled effect of all treatments strategies (relative risk [95% CI], P) now shows a significant reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were confined only to patients with advanced disease for 16 weeks, regardless of which class of drug is used. When considering the effects within each drug family, no class of drug produced a statistically significant reduction in all-cause mortality. The improved survival bore no relationship with the change in 6-minute walk, the primary end point in most of the trials. The impact of vasodilators on long-term survival in pulmonary arterial hypertension remains uncertain. Future trials need to (a) adopt new trial designs that can better address clinical benefits, (b) use new end points that incorporate our best understanding of the disease rather than the ones that are easy to administer, and (c) include longer durations of study and other strategies to clarify if survival is affected. Copyright (c) 2010 Mosby, Inc. All rights reserved.