Clinical application of subtraction CT imaging for evaluation of pulmonary vascular permeability

International Nuclear Information System (INIS)

Kato, Shiro; Asai, Toshihiko; Yatagai, Shigeo; Oonuma, Noboru; Ohno, Kunihiko; Nakamoto, Takaaki; Iizuka, Masahiko

1991-01-01

In this clinical study, one normal subject, one patient with primary interstitial pneumonia, one patient with segmental pneumonia due to Staphylococcus aureus, one patient with post-operative esophageal carcinoma, and two patients with mitral stenosis were studied. Dynamic CT scan images under continuous injection of low osmotic contrast medium were analyzed in series, in an attempt to evaluate vascular permeability quantitatively. The following results were obtained. Subtraction CT scan image 10 minutes after the start of contrast medium injection in two patients with pneumonia, showed a reduction of pulmonary vascular permeability following therapy. Subtraction CT scan image of the patient with post-operative esophageal carcinoma treated with 25 Gy radiation showed a discrepancy between pulmonary vascular permeability and other findings. In hemodynamically stable patients with mitral stenosis, subtraction CT images demonstrated that pulmonary vascular permeability was not affected by pulmonary congestion, irrespective of its severity. (author)

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

OpenAIRE

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 progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). METHODS: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the pre...

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

OpenAIRE

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 progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). Methods Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO i...

Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat

International Nuclear Information System (INIS)

Rabinovitch, M.; Mullen, M.; Rosenberg, H.C.; Maruyama, K.; O'Brodovich, H.; Olley, P.M.

1988-01-01

Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, the authors investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. They instrumented the rats with indwelling cardiovascular catheters and compared the hemodynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. They then determine whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. They observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effects of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both antiotensin II and prostacyclin infusion similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins

Pulmonary vascular anomalies: a review of clinical and radiological findings of cases presenting with different complaints in childhood.

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Nacaroğlu, Hikmet Tekin; Ünsal-Karkıner, Canan Şule; Bahçeci-Erdem, Semiha; Özdemir, Rahmi; Karkıner, Aytaç; Alper, Hüdaver; Can, Demet

2016-01-01

Congenital pulmonary vascular abnormalities arise from several etiologies. These anomalies are difficult to categorize and sorted into distinct classifications. Major pulmonary vascular abnormalities can be ranked as interruption of the main pulmonary artery or its absence, emergence of the left pulmonary artery in the right pulmonary artery, pulmonary venous drainage abnormalities, and pulmonary arteriovenous malformations (PAVMs). Some of the cases are asymptomatic and diagnosed by coincidence, whereas a few of them are diagnosed by typical findings in the newborn and infancy period, symptoms, and radiological appearances. Early diagnosis is important, since death may occur as a result of pulmonary and cardiac pathologies developed in patients with pulmonary vascular anomalies. In this case presentation, the clinical and radiological findings of patients that presented with different complaints and were diagnosed with pulmonary vascular anomalies were introduced.

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

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da Silva Gonçalves Bós, Denielli; Van Der Bruggen, Cathelijne E E; Kurakula, Kondababu; Sun, Xiao-Qing; Casali, Karina R; Casali, Adenauer G; Rol, Nina; Szulcek, Robert; Dos Remedios, Cris; Guignabert, Christophe; Tu, Ly; Dorfmüller, 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

2018-02-27

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 contractility, and reduced RV stiffness, RV hypertrophy, RV fibrosis, RV inflammation, and RV α-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression, as well. Furthermore, PYR reduced pulmonary vascular resistance, RV afterload, and pulmonary vascular remodeling, which was associated with reduced local and systemic inflammation. RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH. © 2017 American Heart Association, Inc.

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

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M. Klein

2008-06-01

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

Effects of irradiation on the pulmonary hemodynamics and the pulmonary vascular permeability

International Nuclear Information System (INIS)

Ohkuda, Kazuhiro; Watanabe, Shinkichi; Okada, Shinichiroh

1982-01-01

In 4 sheeps, base lines of hemodynamics and lymph dynamics were observed for 2 hours, and then 1,000 rad of 60 Co was irradiated to the inferior lobes of the lung. Pulmonary hemodynamics and lymph dynamics were continuously observed, and water and protein permeability of the irradiated pulmonary vessels was evaluated. In 4 control sheeps, no change in pulmonary hemodynamics and lymph dynamics was noted. In the irradiated group, there was no remarkable change in pulmonary hemodynamics for 6 to 8 hours after 60 Co irradiation. Pulmonary lymph flow began to increase 2 hours after irradiation to about 1.7 times the base line level after 4 hours. The increase in pulmonary lymph flow was accompanied by decrease in plasma protein concentration and increase in protein concentration of the lung lymph, resulting in an apparent increase in the ratio of lymph/plasma protein concentration. Water and protein leak from the pulmonary vessels increased. A photomicroscopic observation revealed dilatation of the lymphatic vessels in the lung interstice and a mild pulmonary interstitial edema. Vascular damage, especially due to increased water and protein permeability of the lung capillary vessels, occurred immediately after 60 Co irradiation. (Ueda, J.)

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

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

2017-07-15

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

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

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M. Porres-Aguilar

2013-01-01

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

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

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Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, ppulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

Chronic Embolic Pulmonary Hypertension Caused by Pulmonary Embolism and Vascular Endothelial Growth Factor Inhibition.

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Neto-Neves, Evandro M; Brown, Mary B; Zaretskaia, Maria V; Rezania, Samin; Goodwill, Adam G; McCarthy, Brian P; Persohn, Scott A; Territo, Paul R; Kline, Jeffrey A

2017-04-01

Our understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively. PE + SU rats exhibited sustained pulmonary hypertension (62 ± 13 and 53 ± 14 mmHg at 3 and 6 weeks, respectively) with reduction of the ventriculoarterial coupling in vivo coincident with a large decrement in peak rate of oxygen consumption during aerobic exercise, respectively. PE + SU produced right ventricular hypokinesis, dilation, and hypertrophy observed on echocardiography, and 40% reduction in right ventricular contractile function in isolated perfused hearts. High-resolution computed tomographic pulmonary angiography and Ki-67 immunohistochemistry revealed abundant lung neovascularization and cellular proliferation in PE that was distinctly absent in the PE + SU group. We present a novel rodent model to reproduce much of the known phenotype of CTEPH, including the pivotal pathophysiological role of impaired vascular endothelial growth factor-dependent vascular remodeling. This model may reveal a better pathophysiological understanding of how PE transitions to CTEPH in human treatments. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Pulmonary Vascular Input Impedance is a Combined Measure of Pulmonary Vascular Resistance and Stiffness and Predicts Clinical Outcomes Better than PVR Alone in Pediatric Patients with Pulmonary Hypertension

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Hunter, Kendall S.; Lee, Po-Feng; Lanning, Craig J.; Ivy, D. Dunbar; Kirby, K. Scott; Claussen, Lori R.; Chan, K. Chen; Shandas, Robin

2011-01-01

Background Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated an method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero-harmonic impedance value and PVR, and suggested a correlation between higher harmonic impedance values and pulmonary vascular stiffness (PVS). Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and PVS from a single measurement, and that impedance is a better predictor of disease outcomes compared to PVR. Methods Pressure and velocity waveforms within the main PA were measured during right-heart catheterization of patients with normal PA hemodynamics (n=14) and those with PAH undergoing reactivity evaluation (49 subjects; 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Results Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y=1.095·x+1.381, R2=0.9620). Additionally, the modulus sum of the first two harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (PP/SV) (y=13.39·x-0.8058, R2=0.7962). Amongst a subset of PAH patients (n=25), cumulative logistic regression between outcomes to total indexed impedance was better (RL2=0.4012) than between outcomes and indexed PVR (RL2=0.3131). Conclusions Input impedance can be consistently and easily obtained from PW Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient

An Analysis of Responses to Defibrotide in the Pulmonary Vascular Bed of the Cat.

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Kaye, Alan D; Skonieczny, Brendan D; Kaye, Aaron J; Harris, Zoey I; Luk, Eric J

2016-01-01

Defibrotide is a polydisperse mixture of single-stranded oligonucleotides with many pharmacologic properties and multiple actions on the vascular endothelium. Responses to defibrotide and other vasodepressor agents were evaluated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure. Lobar arterial pressure was increased to a high steady level with the thromboxane A2 analog U-46619. Under increased-tone conditions, defibrotide caused dose-dependent decreases in lobar arterial pressure without altering systemic arterial and left atrial pressures. Responses to defibrotide were significantly attenuated after the administration of the cyclooxygenase inhibitor sodium meclofenamate. Responses to defibrotide were also significantly attenuated after the administration of both the adenosine 1 and 2 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine and 8-(3-chlorostyryl)caffeine. Responses to defibrotide were not altered after the administration of the vascular selective adenosine triphosphate-sensitive potassium channel blocker U-37883A, or after the administration of the nitric oxide synthase inhibitor L-N-(1-iminoethyl)-ornithine. These data show that defibrotide has significant vasodepressor activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to defibrotide are partially dependent on both the activation of the cyclooxygenase enzyme and adenosine 1 and 2 receptor pathways and independent of the activation of adenosine triphosphate-sensitive potassium channels or the synthesis of nitric oxide in the pulmonary vascular bed of the cat.

Pulmonary Hypertension Care Center Network: Improving Care and Outcomes in Pulmonary Hypertension.

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Sahay, Sandeep; Melendres-Groves, Lana; Pawar, Leena; Cajigas, Hector R

2017-04-01

Pulmonary hypertension (PH) is a chronic, progressive, life-threatening disease that requires expert multidisciplinary care. To facilitate this level of care, the Pulmonary Hypertension Association established across the United States a network of pulmonary hypertension care centers (PHCCs) with special expertise in PH, particularly pulmonary arterial hypertension, to raise the overall quality of care and outcomes for patients with this life-threatening disease. Since the inception of PHCCs in September 2014, to date 35 centers have been accredited in the United States. This model of care brings together physicians and specialists from other disciplines to provide care, facilitate basic and clinical research, and educate the next generation of providers. PHCCs also offer additional opportunities for improvements in PH care. The patient registry offered through the PHCCs is an organized system by which data are collected to evaluate the outcomes of patients with PH. This registry helps in detecting variations in outcomes across centers, thus identifying opportunities for improvement. Multiple tactics were undertaken to implement the strategic plan, training, and tools throughout the PHCC network. In addition, strategies to foster collaboration between care center staff and individuals with PH and their families are the cornerstone of the PHCCs. The Pulmonary Vascular Network of the American College of Chest Physicians believes this to be a positive step that will improve the quality of care delivered in the United States to patients with PH. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

International Nuclear Information System (INIS)

Mintun, M.A.; Dennis, D.R.; Welch, M.J.; Mathias, C.J.; Schuster, D.P.

1987-01-01

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-( 68 Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [ 68 Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury

Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

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Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

2017-11-01

To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice.

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Hazarika, Surovi; Van Scott, Michael R; Lust, Robert M; Wingard, Christopher J

2010-01-01

Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intraperitoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K+ depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6±3.9% and 97.7±1.2% to 32±4% and 51±6%, respectively (p<0.05). The sensitivity to acetylcholine was likewise reduced (EC₅₀=0.26±0.05 μM vs. 1.09±0.16 μM, p<0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

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

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Consenso sobre la clasificación de la enfermedad vascular pulmonar hipertensiva en niños: reporte del task force pediátrico del Pulmonary Vascular Research Institute (PVRI Panamá 2011 A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011

Directory of Open Access Journals (Sweden)

María Jesús del Cerro

2012-12-01

Full Text Available Las clasificaciones actuales de la hipertensión pulmonar han contribuido significativamente al conocimiento de la enfermedad vascular pulmonar, han facilitado ensayos farmacológicos y han mejorado nuestro conocimiento de las cardiopatías congénitas del adulto; sin embargo estas clasificaciones no son aplicables completamente a la enfermedad en el niño. La clasificación que aquí se propone se basa principalmente en la práctica clínica. Los objetivos específicos de esta nueva clasificación son mejorar las estrategias diagnósticas, promover la investigación clínica, mejorar nuestro conocimiento de la patogénesis, de la fisiología y de la epidemiología de la enfermedad y orientar el desarrollo de modelos de la enfermedad humana en el laboratorio y estudios en animales; también puede servir como un recurso docente. Se hace énfasis en los conceptos de maladaptación perinatal, alteraciones del desarrollo e hipoplasia pulmonar como factores causantes de la hipertensión pulmonar pediátrica; así mismo, en la importancia de los múltiples síndromes malformativos congénitos, genéticos y cromosómicos en la presentación de la hipertensión pulmonar pediátrica. La enfermedad vascular pulmonar hipertensiva en niños se divide en diez grandes categorías.Current classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It

Increased systemic vascular resistance in neonates with pulmonary hypertension.

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Milstein, J M; Goetzman, B W; Riemenschneider, T A; Wennberg, R P

1979-11-01

The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

Decline in arterial partial pressure of oxygen after exercise: a surrogate marker of pulmonary vascular obstructive disease in patients with atrial septal defect and severe pulmonary hypertension.

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Laksmivenkateshiah, Srinivas; Singhi, Anil K; Vaidyanathan, Balu; Francis, Edwin; Karimassery, Sundaram R; Kumar, Raman K

2011-06-01

To examine the utility of decline in arterial partial pressure of oxygen after exercise as a marker of pulmonary vascular obstructive disease in patients with atrial septal defect and pulmonary hypertension. Treadmill exercise was performed in 18 patients with atrial septal defect and pulmonary hypertension. Arterial blood gas samples were obtained before and after peak exercise. A decline in the arterial pressure of oxygen of more than 10 millimetres of mercury after exercise was considered significant based on preliminary tests conducted on the controls. Cardiac catheterisation was performed in all patients and haemodynamic data sets were obtained on room air, oxygen, and a mixture of oxygen and nitric oxide (30-40 parts per million). There were 10 patients who had more than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise and who had a basal pulmonary vascular resistance index of more than 7 Wood units per square metre. Out of eight patients who had less than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise, seven had a basal pulmonary vascular resistance index of less than 7 Wood units per square metre, p equals 0.0001. A decline in arterial partial pressure of oxygen of more than 10 millimetres of mercury predicted a basal pulmonary vascular resistance index of more than 7 Wood units per square metre with a specificity of 100% and a sensitivity of 90%. A decline in arterial partial pressure of oxygen following exercise appears to predict a high pulmonary vascular resistance index in patients with atrial septal defect and pulmonary hypertension. This test is a useful non-invasive marker of pulmonary vascular obstructive disease in this subset.

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

Science.gov (United States)

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

2017-01-01

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

Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension

NARCIS (Netherlands)

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

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

Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.

Science.gov (United States)

Stenmark, Kurt R; Fagan, Karen A; Frid, Maria G

2006-09-29

Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty.

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Inami, Takumi; Kataoka, Masaharu; Shimura, Nobuhiko; Ishiguro, Haruhisa; Yanagisawa, Ryoji; Taguchi, Hiroki; Fukuda, Keiichi; Yoshino, Hideaki; Satoh, Toru

2013-07-01

This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure. Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted. We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed. Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%). Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Expression of PDGF-beta receptor in broilers with pulmonary hypertension induced by cold temperature and its association with pulmonary vascular remodeling.

Science.gov (United States)

Li, Jin-Chun; Pan, Jia-Qiang; Huang, Guo-Qing; Tan, Xun; Sun, Wei-Dong; Liu, Yan-Juan; Wang, Xiao-Long

2010-02-01

The purpose of the present study was to characterize the relationship between platelet-derived growth factor beta receptor (PDGF-beta receptor) expression and pulmonary vascular remodeling found in broilers subjected to cold temperature beginning at 14 days of age. One hundred and sixty-one-day-old mixed-sex Avian-2000 commercial broilers were randomly divided into a normal temperature group (control) and a cold temperature group (cold). All the birds were brooded in normal temperature up to day 14, with the lighting schedule at 24 h per day. Starting at day 14, birds in the cold group were moved to a pen in the cold house and subjected to low temperature, while birds in the control group were still brooded at normal temperature. On days 14, 23, 30, 37 and 44, the right/total ventricle weight ratio (RV/TV), packed cell volume (PCV), the vessel wall area to vessel total area ratio (WA/TA), mean media thickness in pulmonary arterioles (mMTPA) and the expression of PDGF-beta receptor in pulmonary arterioles were measured, respectively. Cumulative pulmonary hypertension syndrome (PHS) morbidity was recorded in each group. Cool ambient temperature increased PHS morbidity of broilers. The values of WA/TA and mMTPA were also increased significantly compared with control group. PCV values in the cold temperature group were elevated from days 30 to 44, and RV/TV ratios were increased on days 37 and 44. Cold exposure enhanced PDGF-beta receptor expression in pulmonary arterioles, and the PDGF-beta receptor expression was significantly correlated with pulmonary vascular remodeling that was dedicated by increased WA/TA and mMTPA. The results indicated that PDGF-beta and its receptor were involved in the underlying mechanisms of pulmonary vascular remodeling in pulmonary hypertensive broilers. Copyright 2009 Elsevier Ltd. All rights reserved.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

DEFF Research Database (Denmark)

Stenbøg, Elisabeth Vidstid; Steinbruchel, Daniel Andreas; Thomsen, Anne Bloch

2001-01-01

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal....... By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure...... in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations....

Pulmonary circulation

International Nuclear Information System (INIS)

Bongartz, G.; Boos, M.; Scheffler, K.; Steinbrich, W.

1998-01-01

Evaluation of the pulmonary vasculature is mainly indicated in patients with suspected pulmonary thromboembolism. The routine procedure so far is ventilation-perfusion scintigraphy alone or in combination with diagnostic assessment of the legs to rule out deep venous thrombosis. The results are still not reliable for the majority of patients. In the case of equivocal diagnosis, invasive conventional angiography is considered the gold standard. With steady improvements in tomographic imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), non-invasive alternatives to the routine diagnostic work-up are given. Helical CT and CTA techniques are already in clinical use and estimated to sufficiently serve the demands for detection/exclusion of pulmonary thromboembolism. The disadvantages mainly concern peripheral disease and reconstruction artifacts. MRI and MR angiography have been implemented in the diagnosis of pulmonary vascular disease since the introduction of contrast-enhanced MRA. In breath-hold techniques, the entire lung vascularization can be delineated and thromboemboli can be detected. The clinical experience in this field is limited, but MRI has the potential to demonstrate its superiority over CT due to its improved delineation of the vascular periphery and the more comprehensive three-dimensional reconstruction. (orig.)

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

Directory of Open Access Journals (Sweden)

Lili Li

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

Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage.

Science.gov (United States)

Frid, Maria G; Brunetti, Jacqueline A; Burke, Danielle L; Carpenter, Todd C; Davie, Neil J; Reeves, John T; Roedersheimer, Mark T; van Rooijen, Nico; Stenmark, Kurt R

2006-02-01

Vascular remodeling in chronic hypoxic pulmonary hypertension includes marked fibroproliferative changes in the pulmonary artery (PA) adventitia. Although resident PA fibroblasts have long been considered the primary contributors to these processes, we tested the hypothesis that hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage, termed fibrocytes. Using two neonatal animal models (rats and calves) of chronic hypoxic pulmonary hypertension, we demonstrated a dramatic perivascular accumulation of mononuclear cells of a monocyte/macrophage lineage (expressing CD45, CD11b, CD14, CD68, ED1, ED2). Many of these cells produced type I collagen, expressed alpha-smooth muscle actin, and proliferated, thus exhibiting mesenchymal cell characteristics attributed to fibrocytes. The blood-borne origin of these cells was confirmed in experiments wherein circulating monocytes/macrophages of chronically hypoxic rats were in vivo-labeled with DiI fluorochrome via liposome delivery and subsequently identified in the remodeled pulmonary, but not systemic, arterial adventitia. The DiI-labeled cells that appeared in the vessel wall expressed monocyte/macrophage markers and procollagen. Selective depletion of this monocytic cell population, using either clodronate-liposomes or gadolinium chloride, prevented pulmonary adventitial remodeling (ie, production of collagen, fibronectin, and tenascin-C and accumulation of myofibroblasts). We conclude that circulating mesenchymal precursors of a monocyte/macrophage lineage, including fibrocytes, are essential contributors to hypoxia-induced pulmonary vascular remodeling.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

Science.gov (United States)

Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease.

Science.gov (United States)

Gelinas, Jinelle C; Lewis, Nia C; Harper, Megan I; Melzer, Bernie; Agar, Gloria; Rolf, J Douglass; Eves, Neil D

2017-11-01

What is the central question of this study? Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD. What is the main finding and its importance? Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short-term training programmes may not be long enough to improve vascular-related cardiovascular risk in COPD. Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV 1 %pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV 1 %pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow-mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima-media thickness, carotid compliance, distensibility and β-stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power (V̇O2 peak ) was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular

Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension.

Science.gov (United States)

Juratsch, C E; Grover, R F; Rose, C E; Reeves, J T; Walby, W F; Laks, M M

1985-04-01

Distension of the main pulmonary artery (MPA) induces pulmonary hypertension, most probably by neurogenic reflex pulmonary vasoconstriction, although constriction of the pulmonary vessels has not actually been demonstrated. In previous studies in dogs with increased pulmonary vascular resistance produced by airway hypoxia, exogenous arachidonic acid has led to the production of pulmonary vasodilator prostaglandins. Hence, in the present study, we investigated the effect of arachidonic acid in seven intact anesthetized dogs after pulmonary vascular resistance was increased by MPA distention. After steady-state pulmonary hypertension was established, arachidonic acid (1.0 mg/min) was infused into the right ventricle for 16 min; 15-20 min later a 16-mg bolus of arachidonic acid was injected. MPA distension was maintained throughout the study. Although the infusion of arachidonic acid significantly lowered the elevated pulmonary vascular resistance induced by MPA distension, the pulmonary vascular resistance returned to control levels only after the bolus injection of arachidonic acid. Notably, the bolus injection caused a biphasic response which first increased the pulmonary vascular resistance transiently before lowering it to control levels. In dogs with resting levels of pulmonary vascular resistance, administration of arachidonic acid in the same manner did not alter the pulmonary vascular resistance. It is concluded that MPA distension does indeed cause reflex pulmonary vasoconstriction which can be reversed by vasodilator metabolites of arachidonic acid. Even though this reflex may help maintain high pulmonary vascular resistance in the fetus, its function in the adult is obscure.

Pulmonary venous flow index as a predictor of pulmonary vascular resistance variability in congenital heart disease with increased pulmonary flow: a comparative study before and after oxygen inhalation.

Science.gov (United States)

Rivera, Ivan Romero; Mendonça, Maria Alayde; Andrade, José Lázaro; Moises, Valdir; Campos, Orlando; Silva, Célia Camelo; Carvalho, Antonio Carlos

2013-09-01

There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR. Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%. The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension. © 2013, Wiley Periodicals, Inc.

Use of spiral CT angiography to judge central pulmonary vascular involvement from lung cancer

International Nuclear Information System (INIS)

Tan Qunyou; Zhao Shaohong; Wang Fangze; Cai Zulong

2000-01-01

Objective: To evaluate the accuracy of spiral CT angiography (SCTA) in judging central pulmonary vascular involvement from lung cancer located in the hilum and correlate the resultant images with pathologic and surgical findings. Methods: SCTA was done in 33 patients who were preoperatively diagnosed as having lung carcinoma located in the hilum. Contrast medium was injected at a rate of 3 ml/sec with a power injector. The delay time was from 20 to 25 seconds. The pitch was 1 with 3 mm-collimation. Images of central pulmonary arteries and veins were reconstructed with shaded surface display (SSD), maximum intensity projection (MIP), curved planar reformation (CPR), and multi-planar reformation (MPR). Then the relation between tumor and vessels was assessed prospectively on both 3 mm interval axial CT and SCTA images with comparison to subsequent pathologic or surgical findings. Results: (1) In showing the integrity of central pulmonary arteries and veins, images reconstructed by different ways of SCTA had different strong and weak points. (2) The grading standard in this study, with which the relation between vessels and tumor was judged, reflected the basic and common characters of central pulmonary vascular involvement by tumor located in the hilum. compared with axial CT images, SCTA was more accurate in judging the relation between central pulmonary vessels and tumor, and the correlation of SCTA imaging features with pathological patterns and surgical findings was better than that of axial CT images, P < 0.05 and P < 0.0001, respectively. Conclusion: It was feasible to show the relation between central pulmonary vessel and lung cancer located in the hilum with SCTA. And the accuracy of judging the vascular involvement with SCTA was higher than that with axial CT

Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

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Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

2017-05-31

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

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

OpenAIRE

Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

Abstract Background: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods: Prospective registry of patients with left ventricular e...

The adventitia: Essential role in pulmonary vascular remodeling.

Science.gov (United States)

Stenmark, Kurt R; Nozik-Grayck, Eva; Gerasimovskaya, Evgenia; Anwar, Adil; Li, Min; Riddle, Suzette; Frid, Maria

2011-01-01

A rapidly emerging concept is that the vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. It is the most complex compartment of the vessel wall and comprises a variety of cells including fibroblasts, immunomodulatory cells, resident progenitor cells, vasa vasorum endothelial cells, and adrenergic nerves. In response to vascular stress or injury, resident adventitial cells are often the first to be activated and reprogrammed to then influence tone and structure of the vessel wall. Experimental data indicate that the adventitial fibroblast, the most abundant cellular constituent of adventitia, is a critical regulator of vascular wall function. In response to vascular stresses such as overdistension, hypoxia, or infection, the adventitial fibroblast is activated and undergoes phenotypic changes that include proliferation, differentiation, and production of extracellular matrix proteins and adhesion molecules, release of reactive oxygen species, chemokines, cytokines, growth factors, and metalloproteinases that, collectively, affect medial smooth muscle cell tone and growth directly and that stimulate recruitment and retention of circulating inflammatory and progenitor cells to the vessel wall. Resident dendritic cells also participate in "sensing" vascular stress and actively communicate with fibroblasts and progenitor cells to simulate repair processes that involve expansion of the vasa vasorum, which acts as a conduit for further delivery of inflammatory/progenitor cells. This review presents the current evidence demonstrating that the adventitia acts as a key regulator of pulmonary vascular wall function and structure from the "outside in." © 2011 American Physiological Society.

[Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension].

Science.gov (United States)

Wang, Jian-Rong; Zhou, Ying; Sang, Kui; Li, Ming-Xia

2013-02-01

To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH). A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS. The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05). Pulmonary vascular

DSA - a helpful tool in diagnosis of aberrant left pulmonary artery (vascular sling) in adults

International Nuclear Information System (INIS)

Mooyaart, E.L.; Boomsma, J.H.B.; Postmus, P.E.; Formanek, G.A.

1985-01-01

Two new adult patients with aberrant origin of the left pulmonary artery from the right pulmonary artery - pulmonary artery sling - are described, totalling the published adult cases to eight. Differentiation from a mediastinal mass closely mimicking this vascular anomaly is discussed. For the definitive diagnosis, digital subtraction angiography was applied for the first time. The clearest demonstration of the anatomy is in 20-25 0 RPO and 20-25 0 sitting position. The aberrant left pulmonary artery in adults is asymptomatic.

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

Directory of Open Access Journals (Sweden)

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.

Comparison of vascular width and accuracy of subjective assessment of pulmonary flow X-ray films of children with left-right shunt

International Nuclear Information System (INIS)

Hegenbarth, R.; Toeroek, M.; Hannover Medizinische Hochschule

1985-01-01

The authors established a comparative relationship between accuracy of measurement of pulmonary flow and extent of vascular widening in 72 children with Left-Right shunt vitiae; this accuracy of pulmonary flow measurement had been subjectively estimated by 4 investigators without knowing the diagnosis and in comparison to the haemodynamic values (percentage of correct findings). The following procedure was adopted: In a control group of 143 healthy children, we first determined the vascular diameter of the right descending pulmonary artery, of the right upper lobal vein, and of the peripheral vessels in the upper and lower pulmonary fields, at an accurately defined distance from the point of the hilus, and compared with the vascular diameters of the children with left-right shunt, employing the method of discrimination analysis. Comparison of the judgement by the 4 investigators with the degree of increase of the vascular diameters showed an accuracy of 65-100% if the right descending pulmonary artery became wider by 2.6 mm, and an accuracy of 79-95% if the mean vascular width in the right upper field increased by 0.7 mm. The accuracy was 83-94% if the mean vascular width in the right lower field increased by 0.6 mm. Statistical studies also showed that the judgement of the 4 investigators was influenced by different vessels. (orig.) [de

Idiopathic pulmonary fibrosis vs. pulmonary involvement of collagen vascular disease: HRCT findings

International Nuclear Information System (INIS)

Lim, Myung Kwan; Im, Jung Gi; Ahn, Joong Mo; Kim, Ji Hye; Lee, Seon Kyu

1993-01-01

Both idiopathic pulmonary fibrosis (IPF) and pulmonary involvement of collagen vascular disease (CVD) are well known cause of diffuse interstitial lung disease which lead to fibrosis and honeycombing. We analyzed HRCT findings of 33 patients with IPF and 14 patients with CVD in terms of predominant pattern, site of involvement, mediastinal lymph node enlargement, pleural change and pulmonary volume loss. Criteria of mediastinal lymph node enlargement and pleural thickening were 15 mm in long diameter and 3 mm, respectively. Volume loss of the lung was measured by using hilar height ratio (apex to hilum/hilum to diaphragmatic dome). Mean age was 61 years for IPF and 46 years for CVD and male: female ratio was 27:6, 4:10, respectively. Predominant HRCT pattern was honeycombing for IPF (63%), and ground-glass opacity for CVD (66%) (p=0.001). Predominantly, subpleural involvement was seen in 90% for IPF and 74% for CVD. Mediastinal lymph node enlargement was seen in 47% of the patient with IPF and 14% with CVD (p=0.004). Pleural thickening was seen in 97% of the patients with IPF and 42% with CVD (p=0.002). Pleural effusion was seen in 10% of the patients with IPF and 36% with CVD (p=0.009). Hilar height ratio of more than 1.5 was seen in 84% of the patients with IPF and 29% with CVD. In conclusion, our study shows that patients with IPF are prone to have more progressed stage of pulmonary fibrosis than the patients with CVD on HRCT

Idiopathic pulmonary fibrosis vs. pulmonary involvement of collagen vascular disease: HRCT findings

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Lim, Myung Kwan; Im, Jung Gi; Ahn, Joong Mo; Kim, Ji Hye; Lee, Seon Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1993-11-15

Both idiopathic pulmonary fibrosis (IPF) and pulmonary involvement of collagen vascular disease (CVD) are well known cause of diffuse interstitial lung disease which lead to fibrosis and honeycombing. We analyzed HRCT findings of 33 patients with IPF and 14 patients with CVD in terms of predominant pattern, site of involvement, mediastinal lymph node enlargement, pleural change and pulmonary volume loss. Criteria of mediastinal lymph node enlargement and pleural thickening were 15 mm in long diameter and 3 mm, respectively. Volume loss of the lung was measured by using hilar height ratio (apex to hilum/hilum to diaphragmatic dome). Mean age was 61 years for IPF and 46 years for CVD and male: female ratio was 27:6, 4:10, respectively. Predominant HRCT pattern was honeycombing for IPF (63%), and ground-glass opacity for CVD (66%) (p=0.001). Predominantly, subpleural involvement was seen in 90% for IPF and 74% for CVD. Mediastinal lymph node enlargement was seen in 47% of the patient with IPF and 14% with CVD (p=0.004). Pleural thickening was seen in 97% of the patients with IPF and 42% with CVD (p=0.002). Pleural effusion was seen in 10% of the patients with IPF and 36% with CVD (p=0.009). Hilar height ratio of more than 1.5 was seen in 84% of the patients with IPF and 29% with CVD. In conclusion, our study shows that patients with IPF are prone to have more progressed stage of pulmonary fibrosis than the patients with CVD on HRCT.

Hypoxic contraction of cultured pulmonary vascular smooth muscle cells

International Nuclear Information System (INIS)

Murray, T.R.; Chen, L.; Marshall, B.E.; Macarak, E.J.

1990-01-01

The cellular events involved in generating the hypoxic pulmonary vasoconstriction response are not clearly understood, in part because of the multitude of factors that alter pulmonary vascular tone. The goal of the present studies was to determine if a cell culture preparation containing vascular smooth muscle (VSM) cells could be made to contract when exposed to a hypoxic atmosphere. Cultures containing only fetal bovine pulmonary artery VSM cells were assessed for contractile responses to hypoxic stimuli by two methods. In the first, tension forces generated by cells grown on a flexible growth surface (polymerized polydimethyl siloxane) were manifested as wrinkles and distortions of the surface under the cells. Wrinkling of the surface was noted to progressively increase with time as the culture medium bathing the cells was made hypoxic (PO2 approximately 25 mmHg). The changes were sometimes reversible upon return to normoxic conditions and appeared to be enhanced in cells already exhibiting evidence of some baseline tone. Repeated passage in culture did not diminish the hypoxic response. Evidence for contractile responses to hypoxia was also obtained from measurements of myosin light chain (MLC) phosphorylation. Conversion of MLC to the phosphorylated species is an early step in the activation of smooth muscle contraction. Lowering the PO2 in the culture medium to 59 mmHg caused a 45% increase in the proportion of MLC in the phosphorylated form as determined by two-dimensional gel electrophoresis. Similarly, cultures preincubated for 4 h with 32P and then exposed to normoxia or hypoxia for a 5-min experimental period showed more than twice as much of the label in MLCs of the hypoxic cells

ECG Markers of Hemodynamic Improvement in Patients with Pulmonary Hypertension

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Marcin Waligóra

2018-01-01

Full Text Available Introduction. Several diagnostic tests have been recommended for risk assessment in pulmonary hypertension (PH, but the role of electrocardiography (ECG in monitoring of PH patients has not been yet established. Therefore the aim of the study was to evaluate which ECG patterns characteristic for pulmonary hypertension can predict hemodynamic improvement in patients treated with targeted therapies. Methods. Consecutive patients with pulmonary arterial hypertension (PAH or chronic thromboembolic pulmonary hypertension (CTEPH were eligible to be included if they had had performed two consecutive right heart catheterization (RHC procedures before and after starting of targeted therapies. Patients were followed up from June 2009 to July 2017. ECG patterns of right ventricular hypertrophy according to American College of Cardiology Foundation were assessed. Results. We enrolled 80 patients with PAH and 11 patients with inoperable CTEPH. The follow-up RHC was performed within 12.6±10.0 months after starting therapy. Based on median change of pulmonary vascular resistance, we divided our patients into two subgroups: with and without significant hemodynamic improvement. RV1, max⁡RV1,2 + max⁡SI,aVL-SV1, and PII improved along with the improvement of hemodynamic parameters including PVR. They predicted hemodynamic improvement with similarly good accuracy as shown in ROC analysis: RV1 (AUC: 0.75; 95% CI: 0.63–0.84, PII (AUC: 0.67, 95% CI: 0.56–0.77, and max⁡RV1,2+max⁡SI,aVL-SV1 (0.73; 95% CI: 0.63–0.82. In Cox regression only change in RV1 remained significant mortality predictor (HR: 1.12, 95% CI: 1.01–1.24. Conclusion. Electrocardiogram may be useful in predicting hemodynamic effects of targeted therapy in precapillary pulmonary hypertension. Decrease of RV1, max⁡RV1,2+max⁡SI,aVL-SV1, and PII corresponds with hemodynamic improvement after treatment. Of these changes a decrease of R wave amplitude in V1 is associated with better

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

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

1999-12-01

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

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

International Nuclear Information System (INIS)

Meinel, Felix G.; Graef, Anita; Sommer, Wieland H.; Thierfelder, Kolja M.; Reiser, Maximilian F.; Johnson, Thorsten R.C.

2013-01-01

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

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

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Goo, Hyun Woo; Park, Sang Hyub [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of)

2017-11-15

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

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

International Nuclear Information System (INIS)

Goo, Hyun Woo; Park, Sang Hyub

2017-01-01

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

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

Science.gov (United States)

Goo, Hyun Woo; Park, Sang Hyub

2017-11-01

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

MR imaging of the pulmonary vasculature - an update

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Pedersen, Mark R.; Fisher, Mark T. [University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City, Iowa (United States); Beek, Edwin J.R. van [University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City, Iowa (United States); University of Iowa Hospitals and Clinics, JPP 3895, Department of Radiology, Iowa City, Iowa (United States)

2006-06-15

Although the advent of multi-detector row computed tomography (CT) angiography has been at the heart of improving the diagnostic management of pulmonary vascular disease, MR technology has also moved forward. This review outlines the current state of affairs of MR techniques for the assessment of pulmonary vascular diseases such as pulmonary hypertension, pulmonary arteritis and arteriovenous malformations. It highlights the main areas of MR angiography and MR perfusion imaging and discusses novel methods, such as non-contrast enhanced direct thrombus imaging, and will discuss its merits in the context of other diagnostic modalities. (orig.)

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...

Idiopathic pulmonary fibrosis and collagen vascular diseases - high resolution CT findings

International Nuclear Information System (INIS)

Ferreira Neto, Armando Leao; Mogami, Roberto; Marchiori, Edson; Capone, Domenico

1996-01-01

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

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

Directory of Open Access Journals (Sweden)

E.R. Parra

2012-07-01

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

[Pulmonary hypertension of the newborn--recent advances in the management and treatment].

Science.gov (United States)

Vakrilova, L; Radulova, P; Hitrova, St; Slancheva, B

2014-01-01

Pulmonary hypertension of the newborn is a clinical syndrome with diverse etiology in which the transition from fetal circulation with high pulmonary vascular resistance to postnatal circulation with low pulmonary vascular resistance failed. The persistence of high pulmonary vascular pressure leads to right-left shunts and marked cyanosis. Despite of the advances in neonatology, the treatment of some forms of PPHN is often difficult and mortality rate remains high. In infants with PPHN appropriate interventions are critical to reverse hypoxemia, improve pulmonary and systemic perfusion and preserve end-organ function. Our understanding for management of PPHN has evaluated over decades. This review summarizes the current strategies for treatment of pulmonary hypertension of the newborn: general care, cardiovascular support, the advantages and limitations of different ventilatory strategies, oxygen therapy, extracorporal membrane oxygenation, and the evidence-based inhaled nitric oxide therapy. The balance between pulmonary vasoconstrictor and vasodilator mediators plays an important role for pulmonary vascular resistance. Recent studies are designed to develop evidence-based therapies for regulation of pulmonary vascular tone, safe medications for selective pulmonary vasodilatation effective for treatment of PPHN and other forms of pulmonary hypertension in the neonatal intensive care unit.

Redistribution of Extracellular Superoxide Dismutase Causes Neonatal Pulmonary Vascular Remodeling and PH but Protects Against Experimental Bronchopulmonary Dysplasia

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Laurie G. Sherlock

2018-03-01

Full Text Available Background: A naturally occurring single nucleotide polymorphism (SNP, (R213G, in extracellular superoxide dismutase (SOD3, decreases SOD3 matrix binding affinity. Humans and mature mice expressing the R213G SNP exhibit increased cardiovascular disease but decreased lung disease. The impact of this SNP on the neonatal lung at baseline or with injury is unknown. Methods: Wild type and homozygous R213G mice were injected with intraperitoneal bleomycin or phosphate buffered saline (PBS three times weekly for three weeks and tissue harvested at 22 days of life. Vascular and alveolar development were evaluated by morphometric analysis and immunostaining of lung sections. Pulmonary hypertension (PH was assessed by right ventricular hypertrophy (RVH. Lung protein expression for superoxide dismutase (SOD isoforms, catalase, vascular endothelial growth factor receptor 2 (VEGFR2, endothelial nitric oxide synthase (eNOS and guanosine triphosphate cyclohydrolase-1 (GTPCH-1 was evaluated by western blot. SOD activity and SOD3 expression were measured in serum. Results: In R213G mice, SOD3 lung protein expression decreased, serum SOD3 protein expression and SOD serum activity increased compared to wild type (WT mice. Under control conditions, R213G mice developed pulmonary vascular remodeling (decreased vessel density and increased medial wall thickness and PH; alveolar development was similar between strains. After bleomycin injury, in contrast to WT, R213G mice were protected from impaired alveolar development and their vascular abnormalities and PH did not worsen. Bleomycin decreased VEGFR2 and GTPCH-1 only in WT mice. Conclusion: R213G neonatal mice demonstrate impaired vascular development and PH at baseline without alveolar simplification, yet are protected from bleomycin induced lung injury and worsening of pulmonary vascular remodeling and PH. These results show that vessel bound SOD3 is essential in normal pulmonary vascular development, and

Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension.

Science.gov (United States)

Stenmark, Kurt R; Frid, Maria G; Graham, Brian B; Tuder, Rubin M

2018-03-15

Pulmonary hypertension (PH) is the end result of interaction between pulmonary vascular tone and a complex series of cellular and molecular events termed 'vascular remodelling'. The remodelling process, which can involve the entirety of pulmonary arterial vasculature, almost universally involves medial thickening, driven by increased numbers and hypertrophy of its principal cellular constituent, smooth muscle cells (SMCs). It is noted, however that SMCs comprise heterogeneous populations of cells, which can exhibit markedly different proliferative, inflammatory, and extracellular matrix production changes during remodelling. We further consider that these functional changes in SMCs of different phenotype and their role in PH are dynamic and may undergo significant changes over time (which we will refer to as cellular plasticity); no single property can account for the complexity of the contribution of SMC to pulmonary vascular remodelling. Thus, the approaches used to pharmacologically manipulate PH by targeting the SMC phenotype(s) must take into account processes that underlie dominant phenotypes that drive the disease. We present evidence for time- and location-specific changes in SMC proliferation in various animal models of PH; we highlight the transient nature (rather than continuous) of SMC proliferation, emphasizing that the heterogenic SMC populations that reside in different locations along the pulmonary vascular tree exhibit distinct responses to the stresses associated with the development of PH. We also consider that cells that have often been termed 'SMCs' may arise from many origins, including endothelial cells, fibroblasts and resident or circulating progenitors, and thus may contribute via distinct signalling pathways to the remodelling process. Ultimately, PH is characterized by long-lived, apoptosis-resistant SMC. In line with this key pathogenic characteristic, we address the acquisition of a pro-inflammatory phenotype by SMC that is essential

Functional high-resolution computed tomography of pulmonary vascular and airway reactions

International Nuclear Information System (INIS)

Herold, C.J.; Johns Hopkins Medical Institutions, Baltimore, MD; Brown, R.H.; Johns Hopkins Medical Institutions, Baltimore, MD; Johns Hopkins Medical Institutions, Baltimore, MD; Wetzel, R.C.; Herold, S.M.; Zeerhouni, E.A.

1993-01-01

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

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

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Weissmann Norbert

2005-11-01

Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

Science.gov (United States)

Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

2016-01-01

The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

Immunohistochemical examination of plexiform-like complex vascular lesions in the lungs of broiler chickens selected for susceptibility to idiopathic pulmonary arterial hypertension.

Science.gov (United States)

Hamal, Krishna R; Erf, Gisela F; Anthony, Nicholas B; Wideman, Robert F

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance, and by extensive vascular remodelling. In human IPAH patients, remodelling of the pulmonary vasculature results in the formation of plexiform lesions in the terminal pulmonary arterioles. Various molecules are expressed in the human plexiform lesions, including alpha smooth muscle actin, von Willebrand factor, vascular endothelial growth factor, vascular endothelial growth factor receptor type 2, hypoxia inducible factor-1α, survivin, tenascin, collagen, fibronectin, and various immune/inflammatory cells such as, cytotoxic lymphocytes, B lymphocytes, MHC class II cells, and monocytes/macrophages are also present. Plexiform lesions rarely develop in the lungs of laboratory animals, but plexiform-like complex vascular lesions (CVL) do develop spontaneously in the lungs of broiler chickens from an IPAH-susceptible line. To examine angioproliferative and immune-system-related activities associated with CVL in broiler lungs, paraformaldehyde-fixed, paraffin-embedded lung sections from 8-week-old to 24-week-old broiler chickens were stained immunohistochemically using monoclonal or polyclonal antibodies specific for angioproliferative molecules and immune/inflammatory cells. The CVL in the lungs of broiler chickens exhibited positive staining for both angioproliferative molecules and immune/inflammatory cells. These observations combined with the close histological resemblance of broiler CVL to the plexiform lesions of human IPAH patients further validates chickens from our IPAH-susceptible line as an excellent animal model of spontaneous plexogenic arteriopathy.

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

Science.gov (United States)

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

2016-05-01

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

Pulmonary arterial hypertension : an update

NARCIS (Netherlands)

Hoendermis, E. S.

2011-01-01

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

Amplatzer vascular plug IV for occlusion of pulmonary arteriovenous malformations in a patient with cryptogenic stroke

Directory of Open Access Journals (Sweden)

Surendranath R Veeram Reddy

2014-01-01

Full Text Available Paradoxical embolism resulting in cryptogenic stroke has received much attention recently, with the primary focus on patent foramen ovale (PFO. However, it is essential to be vigilant in the search for other causes of paradoxical embolic events, such as pulmonary arteriovenous malformations (PAVM. We describe successful closure of pulmonary AVM with a St Jude Medical (Plymouth, MN Amplatzer TM vascular plug IV. The newer AVP-IV devices can be used for successful embolization of tortuous pulmonary AVM in remote locations where use of other traditional devices may be technically challenging.

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

Science.gov (United States)

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

2012-11-01

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

Estimation of pulmonary vascular resistance in patients with pulmonary fibrosis by phase-contrast magnetic resonance imaging

International Nuclear Information System (INIS)

Ayukawa, Yuichiro; Murayama, Sadayuki; Tsuchiya, Nanae; Yara, Satomi; Fujita, Jiro

2011-01-01

The aim of this study was to assess pulmonary vascular resistance (PVR) in patients with pulmonary fibrosis (PF) by phase-contrast magnetic resonance imaging (MRI). Subjects were 11 healthy volunteers and 11 patients with PF. Using phase-contrast MRI, we measured pulmonary arterial blood flow and calculated the parameters of PVR. Parameters were compared between volunteers and patients using unpaired t-tests. The diagnostic capability of the parameters was evaluated by receiver operating characteristic (ROC) curve analysis. Patients underwent respiratory function tests (RFTs) and chest computed tomography (CT), and they were correlated with MRI parameters. Most MRI parameters were significantly different between volunteers and patients (t-test P values were <0.05 in 9 of 10 parameters). Regarding the RFT and CT visual score, only the %DLco/VA and acceleration time and the CT visual score and average flow volume had significant correlation [r=-0.667 (P=0.024) and r=-0.6 (P=0.031)], respectively. Our findings suggest that PVR derived from phase-contrast MRI is significantly higher in patients with PF than in volunteers. However, all but two of these parameters may not correlate with the severity of PF. (author)

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; Andersen, Kasper Hasseriis; 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...... 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....... 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...

Prospective comparison of helical CT with angiography in pulmonary embolism: global and selective vascular territory analysis. Interobserver agreement

International Nuclear Information System (INIS)

Ruiz, Yolanda; Caballero, Paloma; Caniego, Jose Luis; Friera, Alfonsa; Olivera, Maria Jose; Tagarro, David; Alvarez-Sala, Rodolfo

2003-01-01

The objective of this prospective study was to evaluate the sensitivity, specificity, positive and negative predictive values, and interobserver agreement in the diagnosis of pulmonary embolism with helical CT, compared with pulmonary angiography, for both global results and for selective vascular territories. Helical CT and pulmonary angiography were performed on 66 consecutive patients with clinical suspicion of pulmonary embolism. The exams were blindly interpreted by a vascular radiologist and by two independent thoracic radiologists. Results were analyzed for the final diagnosis as well as separately for 20 different arterial territories in each patient. Pulmonary angiography revealed embolism in 25 patients (38%); 48% were main, 28% lobar, 16% segmental, and 8% subsegmental. The sensitivity, specificity, and positive and negative predictive values of helical CT for observer 1 were, respectively, 91, 81.5, 75, and 94%; in 7.5% of the patients the exam was considered indeterminate. For observer 2 the values were, respectively, 88, 86, 81.5, and 91%; in 9% of the patients the exam was considered indeterminate. Main arteries were considered as non-valuable in 0-0.8%, the lobar in 1.5%, the segmental in 7.5-8.5%, and the subsegmental in 55-60%. Interobserver agreement for the final diagnosis was 80% (kappa 0.65). For each vascular territory, this was 98% (kappa 0.91) for main arteries, 92% (kappa 0.78) for lobar arteries, 79% (kappa 0.56) for segmental arteries, and 59% (kappa 0.21) for subsegmental arteries. Helical CT is a reliable method for pulmonary embolism diagnosis, with good interobserver agreement for main, lobar, and segmental territories. Worse results are found for subsegmental arteries, with high incidence of non-valuable branches and poor interobserver agreement. (orig.)

Pulmonary balloon angioplasty of chronic thromboembolic pulmonary hypertension (CTEPH) in surgically inaccessible cases

International Nuclear Information System (INIS)

Pitton, M.B.; Herber, S.; Thelen, M.; Mayer, E.

2003-01-01

The clinical course of patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) depends on the distribution pattern of the thromboembolic material. In patients with thromboembolic findings in the central pulmonary segments pulmonary thrombendarterectomy (PTE) has excellent results and acceptable operative risk. This paper presents two surgically inaccessable cases that were successfully treated with balloon pulmonary angioplasty. Balloon angioplasty improved parenchymal perfusion, increased cardiac index (ΔCI + 19.2% [Case 1], and + 15.4% [2]), reduced pulmonary vascular resistance during follow-up (ΔPVRI - 25.0% [1] and - 15.9% [2]), and is discussed as an alternative treatment option for cases not suited for surgery. (orig.) [de

Pulmonary capillary pressure in pulmonary hypertension.

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Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

2005-04-01

Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

Pulmonary arterial capacitance in children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease: relation to pulmonary vascular resistance, exercise capacity, and survival.

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Sajan, Imran; Manlhiot, Cedric; Reyes, Janette; McCrindle, Brian W; Humpl, Tilman; Friedberg, Mark K

2011-09-01

Pediatric pulmonary arterial hypertension (PAH), whether idiopathic PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor for mortality in adults with PAH. However, the relation of PAC to pulmonary vascular resistance (PVR), exercise endurance, and survival is poorly defined in children. Catheterization and clinical data of children with PAH (mean pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary shunts, stents, collaterals, or pulmonary venous hypertension were excluded. Primary outcomes were 6-minute walk distance and freedom from death/lung transplant. Forty-seven patients were studied. Nineteen (43%) had iPAH, and 28 (57%) had aPAH (7.1 ± 6.2 vs 8.4 ± 5.5 years, P = .45). Patients with iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC (PACi), lower exercise tolerance, and lower freedom from death/lung transplant than patients with aPAH. Both higher PVRi (P 1.25 mL/mm Hg per square meter and a PVRi >13 Wood units × m(2) were associated with decreased freedom from death or lung transplant. The relationships between PVRi and PACi and survival were independent of each other and not confounded by etiologic group. Low PACi and high PVRi are independently associated with low 6-minute walk distance and survival in children with PAH. Therefore, both should be assessed for better prognostication and management in this high-risk population. Copyright © 2011 Mosby, Inc. All rights reserved.

Pulmonary hypertension of the newborn.

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Stayer, Stephen A; Liu, Yang

2010-09-01

Pulmonary hypertension presenting in the neonatal period can be due to congenital heart malformations (most commonly associated with obstruction to pulmonary venous drainage), high output cardiac failure from large arteriovenous malformations and persistent pulmonary hypertension of the newborn (PPHN). Of these, the most common cause is PPHN. PPHN develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through foetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia; maldevelopment of the pulmonary arteries, seen in meconium aspiration syndrome; and maladaption of the pulmonary vascular bed as occurs with perinatal asphyxia. These newborn patients typically require mechanical ventilatory support and those with underlying lung disease may benefit from high-frequency oscillatory ventilation or extra-corporeal membrane oxygenation (ECMO). Direct pulmonary vasodilators, such as inhaled nitric oxide, have been shown to improve the outcome and reduce the need for ECMO. However, there is very limited experience with other pulmonary vasodilators. The goals for anaesthetic management are (1) to provide an adequate depth of anaesthesia to ablate the rise in PVR associated with surgical stimuli; (2) to maintain adequate ventilation and oxygenation; and (3) to be prepared to treat a pulmonary hypertensive crisis--an acute rise in PVR with associated cardiovascular collapse.

Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

Science.gov (United States)

Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

2018-02-01

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

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

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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.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

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

2017-07-07

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

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

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Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

2015-08-15

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

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

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Manish Sharma

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

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

Science.gov (United States)

Park, Min A; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-11-01

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical

A Potential Role for Exosomal TCTP Export in Vascular Remodeling in Pulmonary Arterial Hypertension.

Science.gov (United States)

Ferrer, Elisabet; Dunmore, Benjamin J; Hassan, Dhiya; Ormiston, Mark L; Moore, Stephen; Deighton, John; Long, Lu; Yang, Xu Dong; Stewart, Duncan J; Morrell, Nicholas W

2018-04-20

Pulmonary arterial hypertension (PAH) is characterized by increased proliferation and resistance to apoptosis of pulmonary vascular cells. Increased expression of translationally controlled tumor protein (TCTP), a pro-survival and anti-apoptotic mediator, has recently been demonstrated in patients with hereditary PAH (HPAH) although its role in the pathobiology of PAH remains unclear. Silencing of TCTP in blood outgrowth endothelial cells (BOECs) isolated from control subjects led to significant changes in morphology, cytoskeletal organization, increased apoptosis and decreased directionality during migration. As TCTP is also localized in extracellular vesicles (EVs), we isolated BOEC-derived EVs (exosomes and microparticles) by sequential ultracentrifugation. BOECs isolated from patients harboring BMPR2 mutations released more exosomes than controls in pro-apoptotic conditions. Furthermore, TCTP protein expression was significantly higher in exosomes compared to microparticles, indicating that TCTP is mainly exported via exosomes. Co-culture assays demonstrated that exosomes transferred TCTP from endothelial cells (ECs) to pulmonary artery smooth muscle cells (PASMCs) suggesting a role for endothelial-derived TCTP in conferring proliferation and apoptotic resistance. In an experimental model of PAH, rats treated with monocrotaline demonstrated increased concentrations of TCTP in the lung and plasma. Consistent with this finding, we observed increased circulating TCTP levels in patients with IPAH compared with controls. Therefore, our data suggests an important role for TCTP in regulating the critical vascular cell phenotypes implicated in the pathobiology of PAH. In addition, this research implicates TCTP as a potential biomarker for the onset and development of PAH.

Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease

NARCIS (Netherlands)

A.R. Kranenburg (Andor); W.I. de Boer (Pim); V.K.T. Alagappan (Vijay Kumar Thyagarajan); P.J. Sterk (Peter); H.S. Sharma (Hari)

2005-01-01

textabstractBACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in

Pulmonary Edema: Classification, Mechanisms of Development, Diagnosis

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V. V. Moroz

2009-01-01

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

Scanning electron microscopy of vascular corrosion casts and histologic examination of pulmonary microvasculature in dogs with dirofilariosis.

Science.gov (United States)

Ninomiya, Hiroyoshi; Wakao, Yoshito

2002-11-01

To characterize structural changes in pulmonary vessels of dogs with dirofilariosis. 8 dogs with dirofilariosis and 2 unaffected control dogs. Pulmonary artery pressure was measured in affected dogs, and dogs then were euthanatized. Scanning electron microscopy was used to examine vascular corrosion casts of pulmonary vasculature. Tissue sections of pulmonary vasculature were evaluated by use of histologic examination. Pulmonary artery pressure was higher in dogs with severely affected pulmonary vessels. In tissue sections, dilatation, as well as lesions in the tunica intima and proliferative lesions resulting in constriction or obstruction, were frequently observed in branches of the pulmonary artery. Numerous dilated bronchial arteries were observed around affected pulmonary arteries. Hyperplastic venous sphincters were observed in small pulmonary veins and venules. In corrosion casts, affected pulmonary lobar arteries had dilatation, pruning, abnormal tapering, constriction, and obstruction. In small arteries and arterioles, surface structures representing aneurisms and edema were seen. Bronchial arteries were well developed and extremely dilated, and they formed numerous anastomoses with pulmonary arteries at all levels, from the pulmonary trunk to peripheral vessels. Capillaries in the lungs were dilated with little structural change. Small pulmonary veins and venules had irregular annular constrictions that were caused by hyperplastic smooth muscle cells of venous sphincters. Scanning electron microscopy of microvascular casts delineated links between the bronchial and pulmonary circulations in dogs with dirofilariosis. Results of scanning electron microscopy provided a structural explanation for the development of pulmonary circulatory disturbances and pulmonary hypertension in dogs affected by dirofilariosis.

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Pulmonary hypertension—“state of the art” management in 2012

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Anita Saxena

2012-01-01

Full Text Available Pulmonary artery hypertension (PAH is a pathological condition of small pulmonary arteries, characterised by vascular proliferation and remodelling. The pulmonary artery pressure and pulmonary vascular resistance progressively rise, leading to right heart failure and death. Pulmonary artery hypertension may be secondary to various conditions, or it may be idiopathic where no underlying cause is identifiable. Earlier, only symptomatic treatment was available for such patients which did not change the natural history of the disease. However, over the years, improvement in understanding the pathogenesis has resulted in the development of targeted approaches to the treatment of PAH. Survival advantage has also been shown with some of the pharmacologic agents. This review article discusses the current management strategy for PAH with special emphasis on an idiopathic variety, in an Indian context.

Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease

NARCIS (Netherlands)

Kranenburg, A. R.; de Boer, W. I.; Alagappan, V. K. T.; Sterk, P. J.; Sharma, H. S.

2005-01-01

BACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and

Pulmonary Hypertension and Pulmonary Vasodilators.

Science.gov (United States)

Keller, Roberta L

2016-03-01

Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

Pulmonary hypertension-"state of the art" management in 2012.

Science.gov (United States)

Saxena, Anita

2012-01-01

Pulmonary artery hypertension (PAH) is a pathological condition of small pulmonary arteries, characterised by vascular proliferation and remodelling. The pulmonary artery pressure and pulmonary vascular resistance progressively rise, leading to right heart failure and death. Pulmonary artery hypertension may be secondary to various conditions, or it may be idiopathic where no underlying cause is identifiable. Earlier, only symptomatic treatment was available for such patients which did not change the natural history of the disease. However, over the years, improvement in understanding the pathogenesis has resulted in the development of targeted approaches to the treatment of PAH. Survival advantage has also been shown with some of the pharmacologic agents. This review article discusses the current management strategy for PAH with special emphasis on an idiopathic variety, in an Indian context. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2017-06-15

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

Lung salvage by pulmonary arterioplasty after vascular injury during video-assisted thoracoscopic surgical right upper lobectomy.

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Petel, M R; Mahieu, J; Baste, J M

2015-01-01

Video Assisted Thoracoscopic Surgical (VATS) lobectomy is now considered feasible and safe. Nevertheless, thoracic surgeons need to be aware of dramatic complications that may occur during this procedure and how best to manage them. We report the case of a severe tear of the right pulmonary artery (PA) during elective VATS upper lobectomy, leading to emergency conversion to control the bleeding. Initial arterial repair was performed by end-to-end anastomosis. Early CT angiography showed thrombosis of the right PA due to anastomotic stenosis. We performed emergency pulmonary arterioplasty with a prosthetic patch to save the right lung. A CT scan days after surgical lung salvage confirmed the permeability of the PA and normal vascularization of the two remaining right lobes. We discuss herein this dramatic complication of VATS lobectomy, the viability of the lung after pulmonary arterial thrombosis, and advocate for early postoperative imaging after pulmonary arterioplasty. Copyright© Acta Chirurgica Belgica.

Juxta-Vascular Pulmonary Nodule Segmentation in PET-CT Imaging Based on an LBF Active Contour Model with Information Entropy and Joint Vector

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Rui Hao

2018-01-01

Full Text Available The accurate segmentation of pulmonary nodules is an important preprocessing step in computer-aided diagnoses of lung cancers. However, the existing segmentation methods may cause the problem of edge leakage and cannot segment juxta-vascular pulmonary nodules accurately. To address this problem, a novel automatic segmentation method based on an LBF active contour model with information entropy and joint vector is proposed in this paper. Our method extracts the interest area of pulmonary nodules by a standard uptake value (SUV in Positron Emission Tomography (PET images, and automatic threshold iteration is used to construct an initial contour roughly. The SUV information entropy and the gray-value joint vector of Positron Emission Tomography–Computed Tomography (PET-CT images are calculated to drive the evolution of contour curve. At the edge of pulmonary nodules, evolution will be stopped and accurate results of pulmonary nodule segmentation can be obtained. Experimental results show that our method can achieve 92.35% average dice similarity coefficient, 2.19 mm Hausdorff distance, and 3.33% false positive with the manual segmentation results. Compared with the existing methods, our proposed method that segments juxta-vascular pulmonary nodules in PET-CT images is more accurate and efficient.

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

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

2017-10-15

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

Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension

Directory of Open Access Journals (Sweden)

David Jenkins

2017-03-01

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

Pulmonary manifestations in collagen vascular diseases; Pulmonale Manifestationen bei Kollagenosen

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

2016-10-15

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

Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension.

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Kumar, Vasanth H; Swartz, Daniel D; Rashid, Nasir; Lakshminrusimha, Satyan; Ma, Changxing; Ryan, Rita M; Morin, Frederick C

2010-09-01

Aerosolized prostacyclin (PGI2) produces selective pulmonary vasodilation in patients with pulmonary hypertension (PH). The response to PGI2 may be increased by phosphodiesterase type 3 inhibitors such as milrinone. We studied the dose response effects of aerosolized PGI2 and aerosolized milrinone both alone and in combination on pulmonary and systemic hemodynamics in newborn lambs with Nomega-nitro-L-arginine methyl ester (L-NAME)-induced PH. We hypothesized that coaerosolization of PGI2 with milrinone would additively decrease pulmonary vascular resistance (PVR), prolong the duration of action of PGI2, and selectively dilate the pulmonary vasculature. Near-term lambs were delivered by C-section and instrumented and PH was induced by L-NAME (bolus 25 mg/kg; infusion 10 mg.kg(-1).h(-1)) and indomethacin. In the first set of experiments, PGI2 was aerosolized at random doses of 2, 20, 100, 200, 500, and 1,000 ng.kg(-1).min(-1) followed by milrinone at doses of 0.1, 1, and 10 microg.kg(-1).min(-1) over 10 min. In the second set of experiments, milrinone at 1 microg.kg(-1).min(-1) was aerosolized in combination with PGI2 at doses of 20, 100, and 200 ng.kg(-1).min(-1) over 10 min. Pulmonary arterial pressures (PAP) and PVR decreased significantly with increasing doses of aerosolized PGI2 and milrinone. The combination of PGI2 and milrinone significantly reduced PAP and PVR more than either of the drugs aerosolized alone. Addition of milrinone significantly increased the duration of action of PGI2. When aerosolized independently, PGI2 and milrinone selectively dilated the pulmonary vasculature but the combination did not. Milrinone enhances the vasodilatory effects of PGI2 on the pulmonary vasculature but caution must be exercised regarding systemic hypotension.

High altitude pulmonary edema: case report

International Nuclear Information System (INIS)

Garcia P, Edward; Contreras Zuniga, Eduardo; Zuluaga, Sandra Ximena

2006-01-01

Acute pulmonary edema is characterized by the accumulation of liquid in the pulmonary interstice, the alveoli, the bronchi and bronchioles; it is from the excessive circulation from the pulmonary vascular system towards extra vascular and the respiratory spaces. The Liquid filters first at the interstitial space to soon perivascular and peri bronchial and, gradually, towards the alveoli and bronchi

Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.

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Babu, K Anand; Supraja, K; Singh, Raj B

2014-01-01

Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

Treatment of Chronic Thromboembolic Pulmonary Hypertension: The Role of Medical Therapy and Balloon Pulmonary Angioplasty.

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Fernandes, Timothy M; Poch, David S; Auger, William R

2016-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value. Previous unblinded cohort trials have assessed PH-targeted medical therapy in various subpopulations of CTEPH patients using epoprostenol, treprostinil, sildenafil, bosentan, and iloprost, each demonstrating measurable pulmonary hemodynamic effects. However, riociguat, a soluble guanylate cyclase stimulator, is the first FDA-approved therapy for inoperable CTEPH to demonstrate both an improvement in functional capabilities (6-minute walk time) as well as significant gains in secondary pulmonary hemodynamic end points in a large placebo-controlled trial. Balloon pulmonary angioplasty is an interventional procedure using telescoping catheters placed in the pulmonary arteries, through which wires and balloons are used to mechanically disrupt chronic clot material and relieve pulmonary vascular obstruction. Contemporary case series from multiple centers worldwide have demonstrated pulmonary hemodynamic improvement with this approach. As a result of these advances, patients with inoperable CTEPH who had few options as recently as 5 years ago now have alternatives with emerging evidence of therapeutic efficacy.

Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak

International Nuclear Information System (INIS)

Dauber, I.M.; Pluss, W.T.; VanGrondelle, A.; Trow, R.S.; Weil, J.V.

1985-01-01

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. The authors tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin ( 131 I) and erythrocytes (/sup 99m/Tc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. They calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability the authors normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. They measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity hydrostatic and high-dose thiourea edema were compared. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 x 10-4 vs. 7.6 +/- 0.9 x 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 x 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity the authors compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water

Fundamentals of management of acute postoperative pulmonary hypertension.

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Taylor, Mary B; Laussen, Peter C

2010-03-01

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

Does exercise pulmonary hypertension exist?

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Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

2016-09-01

The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

Factors affecting regional pulmonary blood flow in chronic ischemic heart disease

International Nuclear Information System (INIS)

Pistolesi, M.; Miniati, M.; Bonsignore, M.

1988-01-01

To assess the effect of left heart disease on pulmonary blood flow distribution, we measured mean pulmonary arterial and wedge pressures, cardiac output, pulmonary vascular resistance, pulmonary blood volume, and arterial oxygen tension before and after treatment in 13 patients with longstanding ischemic heart failure and pulmonary edema. Pulmonary edema was evaluated by a radiographic score, and regional lung perfusion was quantified on a lung scan by the upper to lower third ratio (U:L ratio) of pulmonary blood flow per unit of lung volume. In all cases, redistribution of lung perfusion toward the apical regions was observed; this pattern was not affected by treatment. After treatment, pulmonary vascular pressures, resistance, and edema were reduced, while pulmonary blood volume did not change. At this time, pulmonary vascular resistance showed a positive correlation with the U:L ratio (r = 0.78; P less than 0.01), whereas no correlation was observed between U:L ratio and wedge pressure, pulmonary edema, or arterial oxygen tension. Hence, redistribution of pulmonary blood flow, in these patients, reflects chronic structural vascular changes prevailing in the dependent lung regions

Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

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Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

2013-11-01

Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

Postoperative management of pulmonary endarterectomy and outcome

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Narayana Iyengar Ramakrishna

2010-01-01

Full Text Available Pulmonary artery thromboendarterectomy (PTE has been regarded as a promising, potentially curative surgical procedure. However, PTE is associated with specific postoperative complications, such as reperfusion pulmonary edema and right heart failure leading to a considerable mortality of 7-24%. Despite its limitations PTE is a better surgical alternative to lung transplantation which carries high morbidity and mortality. The aim of the study is to analyze the efficacy, safety, morbidity and survival associated in the postoperative period and quality of life after six months of PTE in Indian patients. Forty-one patients with surgically correctable chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy. All patients were in New York Heart Association (NYHA Class II, III or IV. Preoperative mean pulmonary artery pressure was 40.98 ± 9.29 mmHg and mean pulmonary vascular resistance was 418.39 ± 95.88 dynes/sec/cm -5 . All patients were followed up to six months and a telephonic survey was conducted using a standard questionnaire. They were assessed and classified as per NYHA grading. There was a significant reduction in the mean pulmonary artery pressure (from 40.98 ± 9.29 mmHg to 24.13 ± 7.36 mmHg, P < 0.001 and pulmonary vascular resistance (from 418.39 ± 95.88 dynes/sec/cm -5 to 142.45 ± 36.27 dynes/sec/cm -5 , P < 0.001 with a concomitant increase in the cardiac index (from 1.99 ± 0.20 L/min/m 2 to 3.28 ± 0.56 L/min/m 2 , P < 0.001 during the postoperative period. The mortality rate in our study was 12.19% (five patients. Ninety per cent of the patients reported a significant improvement in the quality of life and exercise tolerance after surgery compared to the preoperative state. Pulmonary endarterectomy is an effective and potentially curative surgical treatment for patients with severe chronic thromboembolic pulmonary hypertension. The current techniques of operation make the procedure relatively safe and

Novel strategies to improve the patency of vascular prostheses

NARCIS (Netherlands)

Heyligers, J.M.M.

2006-01-01

Two novel strategies to improve the patency of vascular prostheses are described in this thesis. To improve the outcome of synthetic vascular bypass surgery, cell seeding is a promising concept that has extensively been investigated and is still evolving. To improve the short term effects due to

Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart Disease.

Science.gov (United States)

Tampakakis, Emmanouil; Shah, Sanjiv J; Borlaug, Barry A; Leary, Peter J; Patel, Harnish H; Miller, Wayne L; Kelemen, Benjamin W; Houston, Brian A; Kolb, Todd M; Damico, Rachel; Mathai, Stephen C; Kasper, Edward K; Hassoun, Paul M; Kass, David A; Tedford, Ryan J

2018-04-01

Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared with isolated postcapillary. However, it remains unclear whether increased mortality in combined post- and precapillary pulmonary hypertension is simply a result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) is a measure of total right ventricular afterload, reflecting both resistive and pulsatile components. We aimed to test whether pulmonary Ea discriminates survivors from nonsurvivors in patients with pulmonary hypertension due to left heart disease and if it does so better than other hemodynamic parameters associated with combined post- and precapillary pulmonary hypertension. We combined 3 large heart failure patient cohorts (n=1036) from academic hospitals, including patients with pulmonary hypertension due to heart failure with preserved ejection fraction (n=232), reduced ejection fraction (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models, pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance and the transpulmonary gradient. Along with pulmonary arterial compliance, pulmonary Ea remained predictive of survival in patients with normal pulmonary vascular resistance. The diastolic pulmonary gradient did not predict mortality. In addition, in a subset of patients with echocardiographic data, Ea and pulmonary arterial compliance were better discriminators of right ventricular dysfunction than the other parameters. Pulmonary Ea and pulmonary arterial compliance more consistently predicted mortality than pulmonary vascular resistance or transpulmonary gradient across a spectrum of left heart disease with pulmonary hypertension, including patients with heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and pulmonary hypertension with a normal pulmonary vascular resistance. © 2018 American Heart Association

DNA Damage and Pulmonary Hypertension

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Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

2016-01-01

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

Upregulation of Klotho potentially inhibits pulmonary vascular remodeling by blocking the activation of the Wnt signaling pathway in rats with PM2.5-induced pulmonary arterial hypertension.

Science.gov (United States)

Cong, Lu-Hong; Du, Shi-Yu; Wu, Yi-Na; Liu, Ying; Li, Tao; Wang, Hui; Li, Gang; Duan, Jun

2018-01-30

We evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub-categorized into different groups. Activation of Wnt/β-catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF levels and PaCO 2 content were higher in the model group, while PaO 2, NO 2 - /NO 3 - content and Klotho level was lower compared to the control group. In comparison to the control group, the model group had decreased Klotho and Bax levels, and elevated Wnt-1, β-catenin, bcl-2, survivin, and PCNA expression, VEGF, IL-6, TNF-α, TNF-β1, and bFGF levels, as well as the percentage of pulmonary artery ring contraction. The Klotho vector, DKK-1 and DKK-1 + Klotho vector groups exhibited reduced cell proliferation, luciferase activity, and the expression of Wnt-1, β-catenin, bcl-2, survivin, and PCNA, as well as shortened S phase compared with the blank and NC groups. Compared with the Klotho vector and DKK-1 groups, the DKK-1 + Klotho vector groups had reduced cell proliferation, luciferase activity, and the expression of Wnt-1, β-catenin, bcl-2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway. © 2018 Wiley Periodicals, Inc.

Use of 3D models of vascular rings and slings to improve resident education.

Science.gov (United States)

Jones, Trahern W; Seckeler, Michael D

2017-09-01

Three-dimensional (3D) printing is a manufacturing method by which an object is created in an additive process, and can be used with medical imaging data to generate accurate physical reproductions of organs and tissues for a variety of applications. We hypothesized that using 3D printed models of congenital cardiovascular lesions to supplement an educational lecture would improve learners' scores on a board-style examination. Patients with normal and abnormal aortic arches were selected and anonymized to generate 3D printed models. A cohort of pediatric and combined pediatric/emergency medicine residents were then randomized to intervention and control groups. Each participant was given a subjective survey and an objective board-style pretest. Each group received the same 20-minutes lecture on vascular rings and slings. During the intervention group's lecture, 3D printed physical models of each lesion were distributed for inspection. After each lecture, both groups completed the same subjective survey and objective board-style test to assess their comfort with and postlecture knowledge of vascular rings. There were no differences in the basic demographics of the two groups. After the lectures, both groups' subjective comfort levels increased. Both groups' scores on the objective test improved, but the intervention group scored higher on the posttest. This study demonstrated a measurable gain in knowledge about vascular rings and pulmonary artery slings with the addition of 3D printed models of the defects. Future applications of this teaching modality could extend to other congenital cardiac lesions and different learners. © 2017 Wiley Periodicals, Inc.

Treatment Effect of Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension Quantified by Automatic Comparative Imaging in Computed Tomography Pulmonary Angiography.

Science.gov (United States)

Zhai, Zhiwei; Ota, Hideki; Staring, Marius; Stolk, Jan; Sugimura, Koichiro; Takase, Kei; Stoel, Berend C

2018-05-01

Balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) can have variable outcomes. To gain more insight into this variation, we designed a method for visualizing and quantifying changes in pulmonary perfusion by automatically comparing computed tomography (CT) pulmonary angiography before and after BPA treatment. We validated these quantifications of perfusion changes against hemodynamic changes measured with right-sided heart catheterization. We studied 14 consecutive CTEPH patients (12 women; age, 70.5 ± 24), who underwent CT pulmonary angiography and right-sided heart catheterization, before and after BPA. Posttreatment images were registered to pretreatment CT scans (using the Elastix toolbox) to obtain corresponding locations. Pulmonary vascular trees and their centerlines were detected using a graph cuts method and a distance transform method, respectively. Areas distal from vessels were defined as pulmonary parenchyma. Subsequently, the density changes within the vascular centerlines and parenchymal areas were calculated and corrected for inspiration level differences. For visualization, the densitometric changes were displayed in color-coded overlays. For quantification, the median and interquartile range of the density changes in the vascular and parenchymal areas (ΔVD and ΔPD) were calculated. The recorded changes in hemodynamic parameters, including changes in systolic, diastolic, and mean pulmonary artery pressure (ΔsPAP, ΔdPAP, and ΔmPAP, respectively) and vascular resistance (ΔPVR), were used as reference assessments of the treatment effect. Spearman correlation coefficients were employed to investigate the correlations between changes in perfusion and hemodynamic changes. Comparative imaging maps showed distinct patterns in perfusion changes among patients. Within pulmonary vessels, the interquartile range of ΔVD correlated significantly with ΔsPAP (R = -0.58, P = 0.03), �

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

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

2016-02-01

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

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

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

2016-01-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

Pulmonary resection can improve treatment outcome in re-treatment pulmonary tuberculosis and its complications

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Ali Rifaat

2014-04-01

Conclusions: Surgery is effective when medical therapy fails to control pulmonary TB and its complications. MDR-TB patients are among those who benefit from pulmonary resection. Postoperative medical therapy is important to improve results and in achieving negative sputum conversion in TB patients including MDR-TB patients.

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

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Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Sarcoidosis with Major Airway, Vascular and Nerve Compromise

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Hiroshi Sekiguchi

2013-01-01

Full Text Available The present report describes a 60-year-old Caucasian woman who presented with progressive dyspnea, cough and wheeze. A computed tomography scan of the chest showed innumerable bilateral inflammatory pulmonary nodules with bronchovascular distribution and a mediastinal and hilar infiltrative process with calcified lymphadenopathy leading to narrowing of lobar bronchi and pulmonary arteries. An echocardiogram revealed pulmonary hypertension. Bronchoscopy showed left vocal cord paralysis and significant narrowing of the bilateral bronchi with mucosal thickening and multiple nodules. Transbronchial biopsy was compatible with sarcoidosis. Despite balloon angioplasty of the left lower lobe and pulmonary artery, and medical therapy with oral corticosteroids, her symptoms did not significantly improve. To the authors’ knowledge, the present report describes the first case of pulmonary sarcoidosis resulting in major airway, vascular and nerve compromise due to compressive lymphadenopathy and suspected concurrent granulomatous infiltration. Its presentation mimicked idiopathic mediastinal fibrosis.

Treatment of pediatric pulmonary hypertension

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Amy Hawkins

2009-06-01

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

Automation process for morphometric analysis of volumetric CT data from pulmonary vasculature in rats.

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Shingrani, Rahul; Krenz, Gary; Molthen, Robert

2010-01-01

With advances in medical imaging scanners, it has become commonplace to generate large multidimensional datasets. These datasets require tools for a rapid, thorough analysis. To address this need, we have developed an automated algorithm for morphometric analysis incorporating A Visualization Workshop computational and image processing libraries for three-dimensional segmentation, vascular tree generation and structural hierarchical ordering with a two-stage numeric optimization procedure for estimating vessel diameters. We combine this new technique with our mathematical models of pulmonary vascular morphology to quantify structural and functional attributes of lung arterial trees. Our physiological studies require repeated measurements of vascular structure to determine differences in vessel biomechanical properties between animal models of pulmonary disease. Automation provides many advantages including significantly improved speed and minimized operator interaction and biasing. The results are validated by comparison with previously published rat pulmonary arterial micro-CT data analysis techniques, in which vessels were manually mapped and measured using intense operator intervention. Published by Elsevier Ireland Ltd.

Maternal PUFA omega-3 supplementation prevents hyperoxia-induced pulmonary hypertension in the offspring.

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Zhong, Ying; Catheline, Daniel; Houeijeh, Ali; Sharma, Dyuti; Du, Li-Zhong; Besengez, Capucine; Deruelle, Philippe; Legrand, Philippe; Storme, Laurent

2018-03-29

Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Polyunsaturated fatty acids ω-3 (PUFA ω-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA ω-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA ω-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH. From embryonic day 15, pregnant Spague-Dawley rats were supplemented daily with PUFA ω-3, PUFA ω-6, or normal saline (0.2 ml/day). After birth, pups were pooled, assigned as 12 per litter, and randomly to either in air or continuous oxygen exposure (FiO2 = 85%) for 20 days, then sacrificed for pulmonary hemodynamic and morphometric analysis. We found that PUFA ω-3 supplementation improved survival, decreased right ventricular systolic pressure and RVH caused by hyperoxia, and significantly improved alveolarization, vascular remodeling, and vascular density. PUFA ω-3 supplementation produced a higher level of total ω-3 in lung tissue and breast milk, and was found reversing the reduced levels of VEGFA, VEGFR-2, ANGPT-1, TIE-2, eNOS, and NO concentrations in lung tissue, and the increased ANGPT-2 levels in hyperoxia-exposed rats. The beneficial effects of PUFA ω-3 in improving lung injuries were also associated with an inhibition of leukocyte infiltration, and reduced expression of proinflammatory cytokines IL-1β, IL-6 and TNF-α. These data indicated that maternal PUFA ω-3 supplementation strategies could effectively protect against infant PH induced by hyperoxia.

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

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Lončarević Olivera

2016-01-01

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

Vascular structure determines pulmonary blood flow distribution

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Hlastala, M. P.; Glenny, R. W.

1999-01-01

Scientific knowledge develops through the evolution of new concepts. This process is usually driven by new methodologies that provide observations not previously available. Understanding of pulmonary blood flow determinants advanced significantly in the 1960s and is now changing rapidly again, because of increased spatial resolution of regional pulmonary blood flow measurements.

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

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

2016-03-15

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

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

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Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

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

Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

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Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R

2016-01-01

Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.

Ghrelin improves vascular autophagy in rats with vascular calcification.

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Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

2017-06-15

This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1 expression selectively in pulmonary artery endothelium

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Leslie A. Blair

2016-10-01

Full Text Available Abstract Background Microparticles (MPs stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH. Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression. Results Pulmonary artery endothelial cells (PAECs were exposed to MPs isolated from the circulation of a rat model of severe PAH. During late-stage (8-weeks PAH, but not early-stage (3-weeks, an increase in ICAM-1 was observed. To determine whether PAH MP-induced ICAM-1 was selective for a specific segment of the pulmonary circulation, pulmonary microvascular endothelial cells (PMVECs were exposed to late-stage PAH MPs and no increase in ICAM-1 was detected. A select population of circulating MPs, the late-stage endoglin + MPs, were used to assess their ability to stimulate ICAM-1 and it was determined that the endoglin + MPs were sufficient to promote ICAM-1 increases in the whole cell, but not surface only expression. Conclusions Late-stage, but not early-stage, MPs in a model of severe PAH selectively induce ICAM-1 in pulmonary artery endothelium, but not pulmonary microcirculation. Further, the selected endoglin + PAH MPs, but not endoglin + MPs from control, are sufficient to promote whole cell ICAM-1 in PAECs. The implications of this work are that MPs in late-stage PAH are capable of inducing ICAM-1 expression selectively in the pulmonary artery. ICAM-1 likely plays a significant role in the observed inflammatory cell recruitment, specifically to vascular lesions in the pulmonary artery and not the pulmonary microcirculation.

X-ray CT evaluation of pulmonary involvements of sarcoidosis

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Nishimura, Koichi; Izumi, Takateru; Kitaichi, Masanori

1987-01-01

We evaluated high resolution CT in 60 patients with histologically diagnosed pulmonary sarcoidosis and, also, studied the relationship between CT and findings in open lung biopsy specimens in 2 cases. The CT findings were as follows: (1) thickening of bronchial wall shadows (27 out of 60 cases, 45.0 %), (2) irregular enlargement of pulmonary vascular shadows (39 cases, 65.0 %), (3) small or large nodular shadows (24 cases, 40.0 %), (4) local volume loss (14 cases, 23.3 %), (5) slightly increased density of localized lung field areas (24 cases, 40.0 %), (6) pleural or subpleural involvement (27 cases, 45.0 %), (7) lymph node enlargement (59 cases, 98.3 %). X-ray CT in 7 patients revealed no evidence of lung field involvement in patients with histologicall confirmed epithelioid cell granuloma in transbronchial lung biopsy specimens. Lesions located within vessels or in the vascular wall, perivascular sheath or alveoli surrounding blood vessels might cause pulmonary vascular shadows to appear swollen on CT. In a comparative study, we found irregular dilatation of pulmonary vascular shadows corresponding to granulomas in the connective tissue sheath of blood vessels. Also, thickening of bronchial wall shadows corresponded to granulomas in and around the bronchial wall. From the point of histopathological view epithelioid cell granulomas in the bronchovascular sheath were most marked in sarcoidosis, and they apperaed on CT as an irregular enlargement of pulmonary vascular shadows and thickening of the bronchial wall. On the other hand, we reported that collapse of alveoli and fibrosis surrounding blood vessels could cause irregular enlargement of pulmonary vascular shadows on CT in idiopathic pulmonary fibrosis (IPF). Such shadows were seen on CT in both sarcoidosis and IPF but the mechanism of their appearance differed. (J.P.N.)

Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model.

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Türck, Patrick; Lacerda, Denise Santos; Carraro, Cristina Campos; de Lima-Seolin, Bruna Gazzi; Teixeira, Rayane Brinck; Poletto Bonetto, Jéssica Hellen; Colombo, Rafael; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

2018-04-10

Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after echocardiography and catheterism. Right ventricular systolic pressure and pressure/time derivatives were increased in monocrotaline animals. The increased right ventricular diameters in monocrotaline groups were reduced with trapidil. Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase activity. Trapidil reduced NADPH oxidases activities and increased the reduced glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV was diminished in monocrotaline groups, whereas expression of RyR and SERCA was enhanced in the groups treated with trapidil. Our data suggest that trapidil induces an improvement in RV remodeling in PAH model, mitigating the progression of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

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Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

2018-04-17

Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

Interleukin-6 overexpression induces pulmonary hypertension.

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Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

2009-01-30

Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

Diagnosis and treatment of pulmonary hypertension in infancy

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Steinhorn, Robin H.

2013-01-01

Normal pulmonary vascular development in infancy requires maintenance of low pulmonary vascular resistance after birth, and is necessary for normal lung function and growth. The developing lung is subject to multiple genetic, pathological and/or environmental influences that can adversely affect lung adaptation, development, and growth, leading to pulmonary hypertension. New classifications of pulmonary hypertension are beginning to account for these diverse phenotypes, and or pulmonary hypertension in infants due to PPHN, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most effective pharmacotherapeutic strategies for infants with PPHN are directed at selective reduction of PVR, and take advantage of a rapidly advancing understanding of the altered signaling pathways in the remodeled vasculature. PMID:24083892

Pulmonary hypertension CT imaging

International Nuclear Information System (INIS)

Nedevska, A.

2013-01-01

Full text: The right heart catheterization is the gold standard in the diagnosis and determines the severity of pulmonary hypertension. The significant technical progress of noninvasive diagnostic imaging methods significantly improves the pixel density and spatial resolution in the study of cardiovascular structures, thus changes their role and place in the overall diagnostic plan. Learning points: What is the etiology, clinical manifestation and general pathophysiological disorders in pulmonary hypertension. What are the established diagnostic methods in the diagnosis and follow-up of patients with pulmonary hypertension. What is the recommended protocol for CT scanning for patients with clinically suspected or documented pulmonary hypertension. What are the important diagnostic findings in CT scan of a patient with pulmonary hypertension. Discussion: The prospect of instantaneous complex - anatomical and functional cardiopulmonary and vascular diagnostics seems extremely attractive. The contrast enhanced multislice computed (CT ) and magnetic resonance imaging are very suitable methods for imaging the structures of the right heart, with the possibility of obtaining multiple projections and three-dimensional imaging reconstructions . There are specific morphological features that, if carefully analyzed, provide diagnostic information. Thus, it is possible to avoid or at least reduce the frequency of use of invasive diagnostic cardiac catheterization in patients with pulmonary hypertension. Conclusion: This review focuses on the use of contrast-enhanced CT for comprehensive evaluation of patients with pulmonary hypertension and presents the observed characteristic changes in the chest, lung parenchyma , the structures of the right half of the heart and pulmonary vessels

Evaluation of the pulmonary vascular bed by digital subtraction angiography

International Nuclear Information System (INIS)

Shikuwa, Masahiro; Asai, Sadahiro; Hara, Shiro; Yamasa, Toshihiko; Miyahara, Yoshiyuki; Hara, Kohei; Nishijima, Kyoji.

1995-01-01

We studied the usefulness of digital subtraction angiography for evaluating the pulmonary capillary bed. Four individuals underwent the procedure. One was a healthy volunteer and the others were patients with chronic pulmonary emphysema. During catheterization, an 8 F balloon catheter was manipulated into the right pulmonary artery. A total of 20 ml of contrast material was injected at a rate of 10 ml/sec at full inspiration. In the normal subject, the capillary bed filled homogeneously and no defect was seen. In the patients, the pulmonary artery was nearly normal, but severe defects were observed in the pulmonary capillaries. Contrast resolvability was greater with digital subtraction pulmonary angiography than with pulmonary perfusion scintigraphy or pulmonary arteriography. This technique makes possible the visual evaluation of the pulmonary capillary bed. (author)

Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients

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Nascimento ESP

2015-03-01

Full Text Available Eloisa Sanches Pereira do Nascimento,1 Luciana Maria Malosá Sampaio,1 Fabiana Sobral Peixoto-Souza,1 Fernanda Dultra Dias,1 Evelim Leal Freitas Dantas Gomes,1 Flavia Regina Greiffo,2 Ana Paula Ligeiro de Oliveira,2 Roberto Stirbulov,3 Rodolfo Paula Vieira,2 Dirceu Costa11Laboratory of Functional Respiratory Evaluation (LARESP, 2Laboratory of Pulmonary and Exercise Immunology (LABPEI, Nove de Julho University (UNINOVE, São Paulo, SP, Brazil; 3Department of Pneumology, Santa Casa University Hospital, São Paulo, SP, BrazilAbstract: Chronic obstructive pulmonary disease (COPD is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8. At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal

Morphometric changes of pulmonary tissues after 20 Gy external irradiation of rat chest

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Cao Zhenshan; Ye Changqing; Yuan Lizhen

1996-01-01

The changes in the main parameters of the lungs at different periods of early stage after local 20 Gy external irradiation of the lungs were measured with morphometric method. The results indicated that the walls of pulmonary arterioles and venules thickened and the vascular permeability index (area of vascular lumen/total area of blood vessel) decreased 7 days after irradiation (P 2 , r = -0.919), indicating that narrowing of the vascular lumen was the result of thickening of the vascular wall. Fifteen days after irradiation, the pulmonary alveolar wall thickened, the area of alveolar cavity decreased and the area of pulmonary interstitial space increased (P<0.01). Electron microscopic examination demonstrated profuse exudation surrounding the microvessels, obvious evacuation of pulmonary type-II cells and increase in cellular types and quantity of pulmonary tissues

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

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

2010-03-01

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

Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

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Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

2008-05-15

Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn

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Mei-Yin Lai

2018-02-01

Full Text Available Persistent pulmonary hypertension (PPHN is a consequence of failed pulmonary vascular transition at birth and leads to pulmonary hypertension with shunting of deoxygenated blood across the ductus arteriosus (DA and foramen ovale (FO resulting in severe hypoxemia, and it may eventually lead to life-threatening circulatory failure. PPHN is a serious event affecting both term and preterm infants in the neonatal intensive care unit. It is often associated with diseases such as congenital diaphragmatic hernia, meconium aspiration, sepsis, congenital pneumonia, birth asphyxia and respiratory distress syndrome. The diagnosis of PPHN should include echocardiographic evidence of increased pulmonary pressure, with demonstrable right-to-left shunt across the DA or FO, and the absence of cyanotic heart diseases. The mainstay therapy of PPHN includes treatment of underlying causes, maintenance of adequate systemic blood pressure, optimized ventilator support for lung recruitment and alveolar ventilation, and pharmacologic measures to increase pulmonary vasodilation and decrease pulmonary vascular resistance. Inhaled nitric oxide has been proved to treat PPHN successfully with improved oxygenation in 60–70% of patients and to significantly reduce the need for extracorporeal membrane oxygenation (ECMO. About 14%–46% of the survivors develop long-term impairments such as hearing deficits, chronic lung disease, cerebral palsy and other neurodevelopmental disabilities.

Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

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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.

Definition, epidemiology and registries of pulmonary hypertension.

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Awdish, R; Cajigas, H

2016-05-01

Pulmonary arterial hypertension (PAH) is a subcategory of pulmonary hypertension (PH) that comprises a group of disorders with similar pulmonary vascular pathology. Though PH is common, the estimated incidence of IPAH is 1-3 cases per million, making it a rare disease. The hemodynamic definition of PAH is a mean pulmonary artery pressure at rest >OR = 25 mm Hg in the presence of a pulmonary capillary wedge pressure pulmonary vascular resistance (PVR) greater than 3 WU. Specific maneuvers during right heart catheterization can be utilized to disclose vasoreactivity and heart failure with preserved ejection fraction, which have implications for management. The inherent complexity in studying a rare disease that exhibits clinical overlap with a common syndrome necessitated the creation of registries. These registries have been indispensable in the characterization and mapping of the natural history of the disease. Equations and risk calculators derived from registries have given clinicians a basis for risk stratification and prognostication. The sequential accumulation of data since the registries began in the 1980s allows for comparisons to be made. Patients who are differentiated by treatment eras and environments can be contrasted. Variability among inclusion criteria similarly allows for comparisons of these subpopulations. This article provides an overview of available registries, highlights insights provided by each and discusses key issues around the interpretation and extrapolation of data from PAH registries. Registries have allowed us to appreciate the improvement in survival afforded by modern therapy and enhanced detection of this disease. Moving forward, a more global approach to registries is needed, as is enhanced collaboration and centralization.

Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.

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Humpl, Tilman; Berger, Rolf M F; Austin, Eric D; Fasnacht Boillat, Margrit S; Bonnet, Damien; Ivy, Dunbar D; Zuk, Malgorzata; Beghetti, Maurice; Schulze-Neick, Ingram

2017-08-01

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

Macitentan for the treatment of pulmonary arterial hypertension

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Kholdani CA

2014-11-01

Full Text Available Cyrus A Kholdani,1 Wassim H Fares,2 Terence K Trow2 1Section of Pulmonary, Critical Care and Sleep Medicine, 2Yale Pulmonary Vascular Disease Program, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA Abstract: Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. Keywords: endothelin, endothelin receptor antagonists, macitentan, pulmonary arterial hypertension

Distinguishing Chronic Thromboembolic Pulmonary Hypertension From Other Causes of Pulmonary Hypertension Using CT.

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Grosse, Alexandra; Grosse, Claudia; Lang, Irene M

2017-12-01

The purpose of this study was to discern imaging findings that separate chronic thromboembolic pulmonary hypertension (CTEPH) from other causes of pulmonary hypertension (PH). A total of 143 patients with proven PH (group 1, pulmonary arterial hypertension; group 2, PH due to left heart disease; group 3, PH due to lung disease; group 4, CTEPH; and group 5, PH due to unclear or multifactorial mechanisms) underwent MDCT angiography. The CT images were assessed for the presence of chronic pulmonary embolism (PE), disparity in segmental vessel size, mosaic perfusion, parenchymal densities, bronchial dilatation, and collateral arteries. The frequencies of vascular signs of chronic PE, disparity in segmental vessel size, mosaic perfusion, parenchymal densities, bronchial collateral arteries, and bronchial dilatation were statistically significantly higher in patients with CTEPH than in patients with nonthromboembolic PH. Vascular signs of chronic PE, mosaic perfusion, parenchymal densities, and bronchial dilatation without bronchial wall thickening were significantly more frequent in patients with CTEPH than in patients in groups 1, 2, 3, and 5. There was no significant difference in the frequencies of bronchial collateral arteries between patients with CTEPH and patients in groups 3 and 5. Most patients with CTEPH have direct vascular signs of chronic PE. Secondary signs include disparity in segmental vessel size, mosaic perfusion pattern, parenchymal densities, collateral bronchial arteries, and bronchial dilatation, which help distinguish CTEPH from other causes of PH.

Alterations of regional pulmonary function in patients with mitral stenosis studied with xenon-133 following surgical treatment

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Kurata, Naohiko

1983-01-01

The purpose of this study is to investigate the regional pulmonary function in mitral stenosis using Xenon-133 before and after surgical treatment. Twenty-seven patients with mitral stenosis have been studied. There were four types of distribution of pulmonary perfusion. According to the increase of pulmonary capillary wedge pressure, the distribution of pulmonary perfusion showed a vertical distribution different from that of normal man, as well known according to the many past reports. But Type IV(PCWP > 30mmHg) showed the distribution uniform throughout the lung. The patients with Type IV had severe pulmonary vascular resistance and abnormal distribution of ventilation. They showed decreased %VC, SaO 2 and increased FRV in the tests of total lung functions. Postoperatively, the distribution of pulmonary perfusion in Type II and Type III returned to normal after 6 - 12 months of surgical treatment, but in the Type IV never returned to normal even after 12 months of surgical treatment. The hemodynamic data in the Type IV after 3 - 6 months of surgical treatment showed the moderate pulmonary hypertension and pulmonary vascular resistance. In total lung function tests, %VC, SaO 2 and FRV were recognized the improvement after surgical treatment, but they retained under normal range even after 12 months of sutgical treatment. The abnormal distribution of ventilation improved to normal distribution after 12 months of surgical treatment. The regional pulmonary function test using Xenon-133 is very beneficial to estimate the severity of mitral stenosis and to expect the effects of surgical treatment on the pulmonary circulation and ventilation. (J.P.N.)

Using Operational Analysis to Improve Access to Pulmonary Function Testing

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Ada Ip

2016-01-01

Full Text Available Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15, with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment.

Development of pulmonary vascular response to oxygen

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Morin, F.C. III; Egan, E.A.; Ferguson, W.; Lundgren, C.E.

1988-01-01

The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs, fetal arterial oxygen tension (Pa O 2 ) increased from 25 to 55 Torr, which increased the proportion or right ventricular output distributed to the fetal lungs from 8 to 59%. In five very immature lambs fetal Pa O 2 increased from 27 to 174 Torr, but the proportion of right ventricular output distributed to the lung did not change. In five of the near-term lambs, pulmonary blood flow was measured. For each measurement of the distribution of blood flow, approximately 8 x 10 5 spheres of 15-μm diameter, labeled with either 153 Gd, 113 Sn, 103 Ru, 95 Nb, or 46 Sc were injected. It increased from 34 to 298 ml · kg fetal wt -1 · min -1 , an 8.8-fold increase. The authors conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth

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

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2012-01-01

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

Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension.

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Zhao, Qiang; Liu, Zixiong; Wang, Zhe; Yang, Cheng; Liu, Jun; Lu, Jun

2007-08-01

Calcitonin gene-related peptide (CGRP) is a potent smooth muscle cell proliferation inhibitor and vasodilator. It is now believed that CGRP plays an important role in maintaining a low pulmonary vascular resistance. We evaluated the therapeutic effect of intravenously administered CGRP-expressing endothelial progenitor cells (EPCs) on left-to-right shunt-induced pulmonary hypertension in rats. Endothelial progenitor cells were obtained from cultured human peripheral blood mononuclear cells. The genetic sequence for CGRP was subcloned into cultured EPCs by human expression plasmid. Pulmonary hypertension was established in immunodeficient rats with an abdominal aorta to inferior vena cava shunt operation. The transfected EPCs were injected through the left jugular vein at 10 weeks after the shunt operation. Mean pulmonary artery pressure and total pulmonary vascular resistance were detected with right cardiac catheterization at 4 weeks. The distribution of EPCs in the lung tissue was examined with immunofluorescence technique. Histopathologic changes in the structure of the pulmonary arteries was observed with electron microscopy and subjected to computerized image analysis. The lungs of rats transplanted with CGRP-expressing EPCs demonstrated a decrease in both mean pulmonary artery pressure (17.64 +/- 0.79 versus 22.08 +/- 0.95 mm Hg; p = 0.018) and total pulmonary vascular resistance (1.26 +/- 0.07 versus 2.45 +/- 0.18 mm Hg x min/mL; p = 0.037) at 4 weeks. Immunofluorescence revealed that intravenously administered cells were incorporated into the pulmonary vasculature. Pulmonary vascular remodeling was remarkably attenuated with the administration of CGRP-expressing EPCs. The transplantation of CGRP-expressing EPCs may effectively attenuate established pulmonary hypertension and exert reversal effects on pulmonary vascular remodeling. Our findings suggest that the therapy based on the combination of both CGRP transfection and EPCs may be a potentially useful

The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes

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Poth, Jens M.; Fini, Mehdi A.; Olschewski, Andrea; El Kasmi, Karim C.; Stenmark, Kurt R.

2014-01-01

Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease. PMID:25416383

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

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Makoto Sahara

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

Estudo angiográfico da circulação pulmonar na tetralogia de Fallot com atresia pulmonar Angiographic study of pulmonary circulation in tetralogy of Fallot with pulmonary atresia

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Marco Aurélio Santos

2005-02-01

Full Text Available OBJETIVO: Identificar os tipos de suprimento sangüíneo vascular pulmonar na tetralogia de Fallot com atresia pulmonar por meio de estudo hemodinâmico. MÉTODOS: Foram submetidos a estudo cineangiocardiográfico 56 pacientes portadores de tetralogia de Fallot com atresia pulmonar com idade de 20 dias a 4 anos e efetuadas injeções de contraste nas seguintes estruturas vasculares: 1 veia pulmonar encunhada, 2 colaterais aortopulmonares, 3 aorta torácica e 4 ductus arteriosus e/ou shunt sistêmico pulmonar. RESULTADOS: Dos 56 pacientes, 15 tinham o suprimento sangüíneo pulmonar através de colaterais aortopulmonares, em 36 o suprimento sangüíneo pulmonar era feito isoladamente pelo ductus arteriosus e em 5 pelo ductus arteriosus e colaterais aortopulmonares. Conforme a presença ou ausência de estruturas vasculares que compõem a circulação pulmonar na tetralogia de Fallot com atresia pulmonar e do tipo de perfusão vascular pulmonar, os doentes foram classificados em 6 tipos. CONCLUSÃO: Em função da grande complexidade e extrema variabilidade do suprimento sangüíneo pulmonar na tetralogia de Fallot com atresia pulmonar torna-se possível, com este tipo de abordagem, a obtenção de informações, suficientemente necessárias, para o correto manuseio clínico-cirúrgico.OBJECTIVE: To identify the types of pulmonary vascular blood supply in tetralogy of Fallot with pulmonary atresia by use of hemodynamic study. METHODS: Fifty-six patients with tetralogy of Fallot and pulmonary atresia, and ages ranging from 20 days to 4 years, underwent cineangiocardiographic study with contrast medium injections in the following vascular structures: 1 wedged pulmonary vein; 2 aortopulmonary collaterals; 3 thoracic aorta; and 4 ductus arteriosus or systemic-pulmonary shunt. RESULTS: In the 56 patients studied, pulmonary blood was supplied as follows: in 15, by aortopulmonary collaterals; in 36, only by the ductus arteriosus; and in 5, by the ductus

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

Signal transduction in the development of pulmonary arterial hypertension

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Malenfant, Simon; Neyron, Anne-Sophie; Paulin, Roxane; Potus, François; Meloche, Jolyane; Provencher, Steeve; Bonnet, Sébastien

2013-01-01

Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients’ conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH. PMID:24015329

Definition and classification of pulmonary hypertension.

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Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

2013-01-01

Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy: Is schistosomiasis hypertension an important confounding factor?

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Mario Terra-Filho

2010-01-01

Full Text Available INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male. The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001. Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for

[The effect of calcitonin gene-related peptide on collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary arterial hypertension].

Science.gov (United States)

Li, Xian-Wei; Du, Jie; Li, Yuan-Jian

2013-03-01

To observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism. Rats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot. Right ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

28. Critical pulmonary valve stenosis: Medical management beyond balloon dilation

Directory of Open Access Journals (Sweden)

Muhammad Arif Khan

2015-10-01

Conclusion: Phentolamine and/or Captopril have a therapeutic role in neonates with critical PVS who remain oxygen dependent after balloon dilation. Both medicationslead to vasodilatation of pulmonary and systemic vascularity. They facilitate inflowto the right ventricle. Right to left shunt across a PFO or/ ASD minimizesand saturation improves leading to a significantreduction in length of hospitalization.

Hemodynamic Characteristics Including Pulmonary Hypertension at Rest and During Exercise Before and After Heart Transplantation

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Lundgren, Jakob; Rådegran, Göran

2015-01-01

Background Little is known about the hemodynamic response to exercise in heart failure patients at various ages before and after heart transplantation (HT). This information is important because postoperative hemodynamics may be a predictor of survival. To investigate the hemodynamic response to HT and exercise, we grouped our patients based on preoperative age and examined their hemodynamics at rest and during exercise before and after HT. Methods and Results Ninety-four patients were evaluated at rest prior to HT with right heart catheterization at our laboratory. Of these patients, 32 were evaluated during slight supine exercise before and 1 year after HT. Postoperative evaluations were performed at rest 1 week after HT and at rest and during exercise at 4 weeks, 3 months, 6 months, and 1 year after HT. The exercise patients were divided into 2 groups based on preoperative age of ≤50 or >50 years. There were no age-dependent differences in the preoperative hemodynamic exercise responses. Hemodynamics markedly improved at rest and during exercise at 1 and 4 weeks, respectively, after HT; however, pulmonary and, in particular, ventricular filling pressures remained high during exercise at 1 year after HT, resulting in normalized pulmonary vascular resistance response but deranged total pulmonary vascular resistance response. Conclusions Our findings suggest that, (1) in patients with heart failure age ≤50 or >50 years may not affect the hemodynamic response to exercise to the same extent as in healthy persons, and (2) total pulmonary vascular resistance may be more adequate than pulmonary vascular resistance for evaluating the exercise response after HT. PMID:26199230

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

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

2012-09-15

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

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

International Nuclear Information System (INIS)

Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo; Ki, Chang Seok

2012-01-01

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

Intraprocedural Safety and Technical Success of the MVP Micro Vascular Plug for Embolization of Pulmonary Arteriovenous Malformations.

Science.gov (United States)

Conrad, Miles B; Ishaque, Brandon M; Surman, Andrew M; Kerlan, Robert K; Hope, Michael D; Dickey, Melissa A; Hetts, Steven W; Wilson, Mark W

2015-11-01

This case series describes early experience, intraprocedural safety, and technical success of the MVP Micro Vascular Plug (MVP; Covidien, Irvine, California) for embolization of 20 pulmonary arteriovenous malformations (PAVMs) using 23 plugs in seven patients with hereditary hemorrhagic telangiectasia. There was no device migration, and all devices were successfully detached electrolytically. Immediate cessation of flow through the feeding artery was achieved in 21 of 23 (91%) deployments. There was one minor complication. This series demonstrates the MVP to be safe and technically successful in the treatment of PAVMs. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Science.gov (United States)

Harting, Matthew T

2017-06-01

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

Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension

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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.

Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension

International Nuclear Information System (INIS)

Froelich, Jens J.; Koenig, Helmut; Knaak, Lennard; Krass, Stefan; Klose, Klaus J.

2008-01-01

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

Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

International Nuclear Information System (INIS)

Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

1984-01-01

The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries

Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

Directory of Open Access Journals (Sweden)

Adriana M Zimnicka

Full Text Available Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX, a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2 also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC. In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness.

Persistent pulmonary hypertension of the newborn.

Science.gov (United States)

Nair, P M C; Bataclan, Maria Flordeliz A

2004-06-01

This article attempts to define a complicated, yet not rare disease of the neonate, which presents with extreme hypoxemia due to increased pulmonary vascular resistance, resulting in diversion of the pulmonary venous blood through persistent fetal channels, namely ductus arteriosus and foramen ovale. Pathophysiology, diagnostic approach and the various modalities of management are analyzed. Persistent pulmonary hypertension of the newborn is multi-factorial, which is reflected in the management as well. These babies are extremely labile to hypoxia and should be stabilized with minimum handling. One hundred percent oxygen and ventilation are the mainstay of treatment. The role of hyperventilation, alkalinization, various non-specific vasodilators such as tolazoline, magnesium sulphate, selective vasodilators such as inhaled nitric oxide, adenosine and the role of high frequency oscillatory ventilation and extra corporeal membrane oxygenation are discussed. With the newer modalities of management, the outlook has improved with mortality of less than 20% and fewer long-term deficits.

The evolution of prostacyclins in pulmonary arterial hypertension: from classical treatment to modern management.

Science.gov (United States)

Burger, Charles D; D'Albini, Lesley; Raspa, Susan; Pruett, Janis A

2016-01-01

Prostacyclins for the treatment of pulmonary arterial hypertension (PAH) have historically been covered under the insurance medical benefit because they require durable medical equipment and are administered by an intravenous, subcutaneous, or inhalation route. However, more treatment options that target the prostacyclin pathway have become available. As the number and type of options expand, an improved understanding of these drugs will aid managed care decision makers in evaluating new treatment options and making clinically sound and cost-effective treatment decisions. PAH is a progressive disease of pulmonary vascular remodeling that increases pulmonary vascular resistance and often results in right-side heart failure and death if left untreated. Adverse event profiles, the complexity of administration modalities, and potential complications must be considered when administering prostacyclin therapy. Traditional modes of administration, with their potential challenges and complications, may have contributed to the unmet need for an oral agent. Another consideration for managed care decision makers is that oral agents are generally covered under the insurance pharmacy benefit. Access to oral medications with long-term outcomes data, as well as the improved convenience of oral therapy, may help patients with PAH maximize function by maintaining a more convenient and consistent therapeutic regimen.

Nitric Oxide-Sensitive Pulmonary Hypertension in Congenital Rubella Syndrome

Directory of Open Access Journals (Sweden)

Francesco Raimondi

2015-01-01

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

Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

Science.gov (United States)

Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

2016-03-01

Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT

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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.)

Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT

International Nuclear Information System (INIS)

Hoey, Edward T.D.; Gopalan, Deepa; Agrawal, S.K.B.; Screaton, Nicholas J.

2009-01-01

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.)

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Tetralogy of Fallot with origin of left pulmonary artery from the ascending aorta

Energy Technology Data Exchange (ETDEWEB)

Robida, A.; Fettich, D.

1985-09-01

Anomalous origin of the left pulmonary artery in tetralogy of Fallot was diagnosed in a 4-year-old boy by cardiac catheterization. Corrective surgery was performed. The child died immediately following the surgical procedure. Postmortem examination revealed obstructive pulmonary vascular disease of the left lung and normal histology of right lung vessels. Early recognition and surgical correction of the anomaly is important with the view to preventing obstructive pulmonary vascular disease.

Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study.

Science.gov (United States)

Siehr, Stephanie L; Feinstein, Jeffrey A; Yang, Weiguang; Peng, Lynn F; Ogawa, Michelle T; Ramamoorthy, Chandra

2016-05-01

During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension. In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered. Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications. Patients 1-5 received phenylephrine 1 μg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 μg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration. After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure. This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic

On the pathologically altered pulmonary pattern

International Nuclear Information System (INIS)

Ginzburg, M.A.; Kinoshenko, Yu.T.

1982-01-01

The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

Directory of Open Access Journals (Sweden)

Chuanyu Wei

Full Text Available Pulmonary hypertension (PH is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC dysfunction and pulmonary arterial smooth muscle cell (PASMC proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4 is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

Hepatopulmonary syndrome induced by common bile duct ligation in a rabbit model: correlation between pulmonary vascular dilatation on thin-section CT and angiography and serum nitrite concentration or endothelial nitric oxide synthase (eNOS)1 expression

International Nuclear Information System (INIS)

Lee, Ki Nam; Yoon, Seong Kuk; Lee, Jin Wha; Kim, Ki Nam; Park, Byung Ho; Kwak, Jong Young; Jeong, Jin Sook; Kim, Young Hoon

2004-01-01

To investigate the correlation between radiologic vascular dilatation and serum nitrite concentration and eNOS expression in the endothelial cell and pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile duct ligation (CBDL). Thin-section CT scans of the lung and pulmonary angiography were obtained 3 weeks after CBDL (n=6), or a sham operation (n=4), and intrapulmonary vasodilatation was assessed. The diameter and tortuosity of peripheral vessels in the right lower lobe by thin-section CT and angiography at the same level of the right lower lobe in all subjects were correlated to serum nitrite concentration and eNOS (endothelial nitric oxide synthase) expression as determined by immunostaining. The diameters of pulmonary vessels on thin-section CT were well correlated with nitrite concentrations in serum (r=0.92, ρ < 0.001). Dilated pulmonary vessels were significantly correlated with an increased eNOS expression (r=0.94, ρ < 0.0001), and the severity of pulmonary vessel tortuosity was found to be well correlated with serum nitrite concentration (r=0.90, ρ < 0.001). The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD was dilated on thin-section CT and on angiographs. Our findings suggest that peripheral pulmonary vascular dilatations are correlated with serum nitrite concentrations and pulmonary eNOS expression

Pulmonary vasculitis: imaging features

International Nuclear Information System (INIS)

Seo, Joon Beom; Im, Jung Gi; Chung, Jin Wook; Goo, Jin Mo; Park, Jae Hyung; Yeon, Kyung Mo; Song, Jae Woo

1999-01-01

Vasculitis is defined as an inflammatory process involving blood vessels, and can lead to destruction of the vascular wall and ischemic damage to the organs supplied by these vessels. The lung is commonly affected. A number of attempts have been made to classify and organize pulmonary vasculitis, but because the clinical manifestations and pathologic features of the condition overlap considerably, these afforts have failed to achieve a consensus. We classified pulmonary vasculitis as belonging to either the angitiis-granulomatosis group, the diffuse pulmonary hemorrhage with capillaritis group, or 'other'. Characteristic radiographic and CT findings of the different types of pulmonary vasculitis are illustrated, with a brief discussion of the respective disease entities

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

Science.gov (United States)

Abramov, Dmitry; Haglund, Nicholas A; Di Salvo, Thomas G

2017-08-01

Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function. We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance. Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m 2 , p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353). Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study.

Science.gov (United States)

Milara, Javier; Ballester, Beatriz; Morell, Anselm; Ortiz, José L; Escrivá, Juan; Fernández, Estrella; Perez-Vizcaino, Francisco; Cogolludo, Angel; Pastor, Enrique; Artigues, Enrique; Morcillo, Esteban; Cortijo, Julio

2018-06-01

Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation ( V )/perfusion ( Q ) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. The study of JAK2 as potential target to treat PH in IPF. JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; Ppulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs) from patients with IPF in vitro treated with the JAK2 inhibitor JSI-124 or siRNA-JAK2 and stimulated with transforming growth factor beta. Both JSI-124 and siRNA-JAK2 inhibited the HPAEC to mesenchymal transition and the HPASMCs to myofibroblast transition and proliferation. JAK2 inhibition induced small PA relaxation in precision-cut lung slice experiments. PA relaxation was dependent of the large conductance calcium-activated potassium channel (BK Ca ). JAK2 inhibition activated BK Ca channels and reduced intracellular Ca 2+ . JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V / Q mismatching in rats. The animal studies followed the ARRIVE guidelines. JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Tetralogy of Fallot with origin of left pulmonary artery from the ascending aorta

International Nuclear Information System (INIS)

Robida, A.; Fettich, D.

1985-01-01

Anomalous origin of the left pulmonary artery in tetralogy of Fallot was diagnosed in a 4-year-old boy by cardiac catheterization. Corrective surgery was performed. The child died immediately following the surgical procedure. Postmortem examination revealed obstructive pulmonary vascular disease of the left lung and normal histology of right lung vessels. Early recognition and surgical correction of the anomaly is important with the view to preventing obstructive pulmonary vascular disease. (orig.)

Association between HCV induced mixed cryoglobulinemia and pulmonary affection: The role of TNF-alpha in the pathogenesis of pulmonary changes

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AbdelBaset M. Saleh

2014-01-01

Conclusions: The results of this study suggest that pulmonary involvement is common in patients with chronic HCV infection and mixed cryoglobulinemia. Cryoglobulinemia may lead to pulmonary involvement through vascular and interstitial deposition of cryoglobulins, which results in impaired gas exchange and airway affection.

Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction.

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Mishra, Abhi; Kumar, Bhupesh; Dutta, Vikas; Arya, V K; Mishra, Anand Kumar

2016-06-01

To compare the effects of levosimendan with milrinone in cardiac surgical patients with pulmonary hypertension and left ventricular dysfunction. A prospective, randomized study. Tertiary care teaching hospital. The study included patients with valvular heart disease and pulmonary artery hypertension undergoing valve surgery. Forty patients were allocated randomly to receive either milrinone, 50 µg/kg bolus followed by infusion at a rate of 0.5 µg/kg/min (group 1), or levosimendan, 10 µg/kg bolus followed by infusion at a rate of 0.1 µg/kg/min (group 2) for 24 hours after surgery. Hemodynamic parameters were measured using a pulmonary artery catheter, and biventricular functions were assessed using echocardiography. Mean pulmonary artery pressures and the pulmonary vascular resistance index were comparable between the 2 groups at several time points in the intensive care unit. Biventricular function was comparable between both groups. Postcardiopulmonary bypass right ventricular systolic and diastolic functions decreased in both groups compared with baseline, whereas 6 hours postbypass left ventricular ejection fraction improved in patients with stenotic valvular lesions. Levosimendan use was associated with higher heart rate, increased cardiac index, decreased systemic vascular resistance index, and increased requirement of norepinephrine infusion compared with milrinone. The results of this study demonstrated that levosimendan was not clinically better than milrinone. Levosimendan therapy resulted in a greater increase in heart rate, decrease in systemic vascular resistance, and a greater need for norepinephrine than in patients who received milrinone. Copyright © 2016 Elsevier Inc. All rights reserved.

Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

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Juliano Gomes da Penha

2015-01-01

Full Text Available Background:Transposition of the great arteries (TGA is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level.Objective:Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure.Methods:Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included.Results:After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced.Conclusion:The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis.

Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

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Pfister, Sandra L.

2011-01-01

Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis.

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Kosanovic, Djuro; Luitel, Himal; Dahal, Bhola Kumar; Cornitescu, Teodora; Janssen, Wiebke; Danser, A H Jan; Garrelds, Ingrid M; De Mey, Jo G R; Fazzi, Gregorio; Schiffers, Paul; Iglarz, Marc; Fischli, Walter; Ghofrani, Hossein Ardeschir; Weissmann, Norbert; Grimminger, Friedrich; Seeger, Werner; Reiss, Irwin; Schermuly, Ralph Theo

2015-10-01

Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.Chymase inhibition resulted in attenuation of pulmonary hypertension and pulmonary fibrosis, as evident from improved haemodynamics, decreased right ventricular remodelling/hypertrophy, pulmonary vascular remodelling and lung fibrosis. These beneficial effects were associated with a strong tendency of reduction in mast cell number and activity, and significantly diminished chymase expression levels. Mechanistically, chymase inhibition led to attenuation of transforming growth factor β1 and matrix-metalloproteinase-2 contents in the lungs. Furthermore, chymase inhibition prevented big endothelin-1-induced vasoconstriction of the pulmonary arteries.Therefore, chymase plays a role in the pathogenesis of pulmonary hypertension associated with pulmonary fibrosis and may represent a promising therapeutic target. In addition, this study may provide valuable insights on the contribution of chymase in the pulmonary hypertension context, in general, regardless of the pulmonary hypertension form. Copyright ©ERS 2015.

Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep

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Seedorf, Gregory J.; Brown, Alicia; Roe, Gates; O'Meara, Meghan C.; Gien, Jason; Tang, Jen-Ruey; Abman, Steven H.

2011-01-01

Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P growth by 68% (P growth was reduced in IUGR PAECs by 29% at baseline (P growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR. PMID:21873446

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

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

2017-01-01

Fractal analysis of canine pulmonary vessels could allow quantification of their space-filling properties. Aims of this prospective, analytical, cross-sectional study were to describe methods for reconstructing three dimensional pulmonary arterial vascular trees from computed tomographic pulmonary...... angiogram, applying fractal analyses of these vascular trees in dogs with and without diseases that are known to predispose to thromboembolism, and testing the hypothesis that diseased dogs would have a different fractal dimension than healthy dogs. A total of 34 dogs were sampled. Based on computed...... for each dog using a semiautomated segmentation technique. Vascular three-dimensional reconstructions were then evaluated using fractal analysis. Fractal dimensions were analyzed, by group, using analysis of variance and principal component analysis. Fractal dimensions were significantly different among...

RhoA–Rho kinase and Platelet Activating Factor Stimulation of Ovine Fetal Pulmonary Vascular Smooth Muscle Cell Proliferation

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Renteria, Lissette S.; Austin, Monique; Lazaro, Mariecon; Andrews, Mari Ashley; Lustina, Jennessee; Raj, J. Usha; Ibe, Basil O.

2013-01-01

Objectives Platelet Activating Factor (PAF) is produced by pulmonary vascular smooth muscle Cells (PVSMC). We studied effect of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand a role for RhoA/Rho kinase on PAF-induced ovine fetal pulmonary vascular remodeling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signaling, to induce arterial (SMC-PA) and venous (SMC-PV) growth in the hypoxic lung environment of the fetus in utero. Materials and methods Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell growth and PAFR expression were studied by DNA synthesis, Western and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation was also studied. Results Hypoxia increased PVSMC proliferation and the Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly down-regulated in both cell types by both Y-27632 and HA-1077 with comparable profiles. Also cells treated with Y-27632 showed less PAF receptor fluorescence with significant disruption of the cell morphology. Conclusions Our results show that Rho kinase nonspecifically modulates PAFR-mediated responses via a translational modification of PAFR protein and suggest that, in vivo, activation of Rho kinase by PAF may be one other pathway to sustain PAFR-mediated PVSMC growth. PMID:24033386

RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation.

Science.gov (United States)

Renteria, L S; Austin, M; Lazaro, M; Andrews, M A; Lustina, J; Raj, J U; Ibe, B O

2013-10-01

Platelet-activating factor (PAF) is produced by pulmonary vascular smooth muscle cells (PVSMC). We studied effects of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand the role of RhoA/Rho kinase on PAF-induced ovine foetal pulmonary vascular remodelling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signals, to induce arterial (SMC-PA) and venous (SMC-PV) cell proliferation in the hypoxic lung environment of the foetus, in utero. Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell population expansion, and PAFR expression, were studied by DNA synthesis, western blot analysis and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation were also investigated. Hypoxia increased PVSMC proliferation and Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly downregulated in both cell types by both Y-27632 and HA-1077, with comparable profiles. Also, cells treated with Y-27632 had less PAF receptor fluorescence with significant disruption of cell morphology. Our results show that Rho kinase non-specifically modulated PAFR-mediated responses by a translational modification of PAFR protein, and suggest that, in vivo, activation of Rho kinase by PAF may be a further pathway to sustain PAFR-mediated PVSMC proliferation. © 2013 John Wiley & Sons Ltd.

A study on the pulmonary mean transit time and the pulmonary blood volume by RI-cardiogram

International Nuclear Information System (INIS)

Ushio, Norio

1987-01-01

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

Effect of carbon dioxide inhalation on pulmonary hypertension induced by increased blood flow and hypoxia

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I-Chun Chuang

2011-08-01

Full Text Available There is now increasing evidence from the experimental and clinical setting that therapeutic hypercapnia from intentionally inspired carbon dioxide (CO2 or lower tidal volume might be a beneficial adjunct to the strategies of mechanical ventilation in critical illness. Although previous reports indicate that CO2 exerts a beneficial effect in the lungs, the pulmonary vascular response to hypercapnia under various conditions remains to be clarified. The purpose of the present study is to characterize the pulmonary vascular response to CO2 under the different conditions of pulmonary hypertension secondary to increased pulmonary blood flow and secondary to hypoxic pulmonary vasoconstriction. Isolated rat lung (n = 32 was used to study (1 the vasoactive action of 5% CO2 in either N2 (hypoxic-hypercapnia or air (normoxic-hypercapnia at different pulmonary arterial pressure levels induced by graded speed of perfusion flow and (2 the role of nitric oxide (NO in mediating the pulmonary vascular response to hypercapnia, hypoxia, and flow-associated pulmonary hypertension. The results indicated that inhaled CO2 reversed pulmonary hypertension induced by hypoxia but not by flow alteration. Endogenous NO attenuates hypoxic pulmonary vasoconstriction but does not augment the CO2-induced vasodilatation. Acute change in blood flow does not alter the endogenous NO production.

N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease

DEFF Research Database (Denmark)

Wittstock, Antje; Burkert, Magdalena; Zidek, Walter

2009-01-01

Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity in these ...

Comparison between the radiological manifestations of thoracic involvement in collagen vascular diseases and idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Kirova, G.; Rashkov, R.; Georgiev, O.

2002-01-01

The purpose of the study is to compare the presentation and distribution of lung abnormalities seen in Collagen Vascular Diseases (CVD) with those specifics for Idiopathic Pulmonary Fibrosis (IPF). The HRCT scans of 92 patients fulfilling the ARA criteria's for the diagnosis of four different CVD were reviewed and compared with those of 18 patients with IPF. The presentations of three main patterns of lung disease were assessed into the both groups. In order to find out the trend distribution in each disease, the grade and severity of presentation for the main abnormalities were assessed, using a scoring system.The incidence of reticular lung abnormalities for the group of IPF is 100 % versus 57.3 % for the CVD (p<0.0009). At the same time CVD, except for PSS, had a low incidence of reticular diseases (37 %). The incidence of alveolar abnormalities in CVD (57.3 %) were similar as these in IPF (66.6 %) (p=NS). The severity of the disease was greatest in IPF and PSS without significant difference between them. Nevertheless of uniform character of the abnormalities in the rest of CVD, they were presented with lesser degree and severity. The main abnormalities, seen in pulmonary parenchyma in patients with IPF and CVD were similar but with different grade, severity and distribution. (authors)

Clinical application of the amplatzer vascular plug in the embolization of vascular malformations associated with congenital heart diseasee

International Nuclear Information System (INIS)

Pan Xin; Wang Cheng; Lu Jing; Wu Weihua; Fang Weiyi

2009-01-01

Objective: To evaluate the clinical efficacy of percutaneous transcatheter embolization by using Amplatzer vascular plug (AVP) for the treatment of vascular malformations associated with congenital heart diseases. Methods: During the period of June 2006-June 2008, 12 patients with congenital heart disease accompanied by vascular malformations received transcatheter occlusion of the anomalous vessels with AVP. The vascular malformations included solitary or multiple saccular pulmonary arteriovenous malformation (n = 7), coronary artery fistula (n = 2) and major aortopulmonary collaterals concomitant with severe Fallot' s tetralogy (n = 3). All patients were screened with transthoracic echocardiography (TTE) and thoracic CT angiography (CTA), and all the diagnoses were confirmed by routine cardioangiography. Results: Transcatheter occlusion of vascular malformations with AVP was successfully accomplished in all 12 patients. An angiographic check immediately after the procedure showed that complete occlusion was obtained in all patients and no embolism,migration or residual shunt were seen. Sixteen anomalous vessels were occluded. The mean internal diameter of these vessels was (5.2 ± 1.9) mm,while the mean diameter of AVP used was (9.2 ± 2.4) mm. After the operation (mean 3 months), the follow-up echocardiography and/or thoracic CT angiography showed that in all patients the occlusion remained in satisfactory condition and no residual shunt was found. Conclusions: Percutaneous transcatheter closure of congenital vascular malformations with AVP is technically feasible and clinically effective, this treatment can markedly improve patient's living quality and it is well worth extending its clinical application. (authors)

When a pulmonary embolism is not a pulmonary embolism: a rare case of primary pulmonary leiomyosarcoma

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Nargiz Muganlinskaya

2015-12-01

Full Text Available Arterial leiomyosarcomas account for up to 21% of vascular leiomyosarcomas, with 56% of arterial leiomyosarcomas occurring in the pulmonary artery. While isolated cases of primary pulmonary artery leiomyosarcoma document survival up to 36 months after treatment, these uncommon, aggressive tumors are highly lethal, with 1-year survival estimated at 20% from the onset of symptoms. We discuss a rare case of a pulmonary artery leiomyosarcoma that was originally diagnosed as a pulmonary embolism (PE. A 72-year-old Caucasian female was initially diagnosed with ‘saddle pulmonary embolism’ based on computerized tomographic angiography of the chest 2 months prior to admission and placed on anticoagulation. Dyspnea escalated, and serial computed tomography scans showed cardiomegaly with pulmonary emboli involving the right and left main pulmonary arteries with extension into the right and left upper and lower lobe branches. An echocardiogram on admission showed severe pulmonary hypertension with a pulmonary artery pressure of 82.9 mm Hg, and a severely enlarged right ventricle. Respiratory distress and multiorgan failure developed and, unfortunately, the patient expired. Autopsy showed a lobulated, yellow mass throughout the main pulmonary arteries measuring 13 cm in diameter. The mass extended into the parenchyma of the right upper lobe. On microscopy, the mass was consistent with a high-grade primary pulmonary artery leiomyosarcoma. Median survival of patients with primary pulmonary artery leiomyosarcoma without surgery is one and a half months, and mortality is usually due to right-sided heart failure. Pulmonary artery leiomyosarcoma is a rare but highly lethal disease commonly mistaken for PE. Thus, we recommend clinicians to suspect this malignancy when anticoagulation fails to relieve initial symptoms. In conclusion, early detection and suspicion of pulmonary artery leiomyosarcoma should be considered in patients refractory to anticoagulation

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.

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Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2017-07-16

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n -3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR ( n = 8, p DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

Cardiac magnetic resonance imaging-derived pulmonary artery distensibility index correlates with pulmonary artery stiffness and predicts functional capacity in patients with pulmonary arterial hypertension

International Nuclear Information System (INIS)

Kang, Ki-Woon; Chang, Hyuk-Jae; Kim, Young-Jin; Choi, Byoung-Wook; Yang, Woo-In; Shim, Chi-Young; Ha, Jongwon; Chung, Namsik; Lee, Hye-Sun

2011-01-01

Increased stiffness of the pulmonary vascular bed is known to increase mortality in patients with pulmonary arterial hypertension (PAH); and pulmonary artery (PA) stiffness is also thought to be associated with exercise capacity. The purpose of the present study was to investigate whether cardiac magnetic resonance imaging (CMRI)-derived PA distensibility index correlates with PA stiffness estimated on right heart catheterization (RHC) and predicts functional capacity (FC) in patients with PAH. Thirty-five consecutive PAH patients (23% male, mean age, 44±13 years; 69% idiopathic) underwent CMRI, RHC, and 6-min walk test (6MWT). PA distensibility indices were derived from cross-sectional area change (%) in the transverse view, perpendicular to the axis of the main PA, on CMRI [(maximum area-minimum area)/minimum area during cardiac cycle]. Among the PA stiffness indices, pulmonary vascular resistance (PVR) and PA capacitance were calculated using hemodynamic dataset from RHC. CMRI-derived PA distensibility was inversely correlated with PVR (R 2 =0.34, P 2 =0.35, P 2 =0.61, P<0.001). Furthermore, PA distensibility <20% predicted poor FC (<400 m in 6MWT) with a sensitivity of 82% and a specificity of 94%. Non-invasive CMRI-derived PA distensibility index correlates with PA stiffness and can predict FC in patients with PAH. (author)

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

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Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

2005-11-01

Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

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Johns, Christopher S.; Swift, Andrew J.; Hughes, Paul J.C. [University of Sheffield (United Kingdom); Ohno, Yoshiharu [Division of Functional and Diagnostic Imaging Research, Department of Radiology, KobeUniversity Graduate School of Medicine, Kobe, Hyogo (Japan); Schiebler, Mark [UW-Madison School of Medicine and Public Health, Madison, WI (United States); Wild, Jim M., E-mail: j.m.wild@sheffield.ac.uk [University of Sheffield (United Kingdom)

2017-01-15

Highlights: • This article represents an overview of the methodology and clinical applications of pulmonary MRA and perfusion imaging. • Both contrast enhanced and non-contrast enhanced metholodology for MRA and perfusion are covered. • The current clinical uses and future directions of MRA and MR perfusion are discussed. - Abstract: The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology.

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

International Nuclear Information System (INIS)

Johns, Christopher S.; Swift, Andrew J.; Hughes, Paul J.C.; Ohno, Yoshiharu; Schiebler, Mark; Wild, Jim M.

2017-01-01

Highlights: • This article represents an overview of the methodology and clinical applications of pulmonary MRA and perfusion imaging. • Both contrast enhanced and non-contrast enhanced metholodology for MRA and perfusion are covered. • The current clinical uses and future directions of MRA and MR perfusion are discussed. - Abstract: The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology.

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

Science.gov (United States)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease.

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Anthony M Szema

Full Text Available Idiopathic pulmonary fibrosis (IPF and chronic obstructive pulmonary disease (COPD are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH. Nuclear Factor of Activated T-cells (NFAT is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1 VIP inhibits NFAT isoform c3 (NFATc3 activity in pulmonary vascular smooth muscle cells; 2 lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3 VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients

Influence of Distal Resistance and Proximal Stiffness on Hemodynamics and RV Afterload in Progression and Treatments of Pulmonary Hypertension: A Computational Study with Validation Using Animal Models

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Zhenbi Su

2013-01-01

Full Text Available We develop a simple computational model based on measurements from a hypoxic neonatal calf model of pulmonary hypertension (PH to investigate the interplay between vascular and ventricular measures in the setting of progressive PH. Model parameters were obtained directly from in vivo and ex vivo measurements of neonatal calves. Seventeen sets of model-predicted impedance and mean pulmonary arterial pressure (mPAP show good agreement with the animal measurements, thereby validating the model. Next, we considered a predictive model in which three parameters, PVR, elastic modulus (EM, and arterial thickness, were varied singly from one simulation to the next to study their individual roles in PH progression. Finally, we used the model to predict the individual impacts of clinical (vasodilatory and theoretical (compliance increasing PH treatments on improving pulmonary hemodynamics. Our model (1 displayed excellent patient-specific agreement with measured global pulmonary parameters; (2 quantified relationships between PVR and mean pressure and PVS and pulse pressure, as well as studiying the right ventricular (RV afterload, which could be measured as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves; (3 qualitatively confirmed the derangement of vascular wall shear stress in progressive PH; and (4 established that decreasing proximal vascular stiffness through a theoretical treatment of reversing proximal vascular remodeling could decrease RV afterload.

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

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

1993-03-01

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

Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation

DEFF Research Database (Denmark)

Hebert, Anders; Mikkelsen, Ulla Ramer; Thilen, Ulf

2014-01-01

a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim......BACKGROUND: The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays...... of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients. METHODS AND RESULTS: Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality...

Eisenmenger syndrome and idiopathic pulmonary arterial hypertension: do parenchymal lung changes reflect aetiology?

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Griffin, N.; Allen, D.; Wort, J.; Rubens, M.; Padley, S.

2007-01-01

Aim: To document the pulmonary vascular changes on thin-section computed tomography (CT) in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension, and to determine whether there is any correlation with pulmonary arterial pressures or the aetiology of pulmonary hypertension. Material and methods: From the National Pulmonary Hypertension Database, we identified eight patients with idiopathic pulmonary arterial hypertension and 20 patients with Eisenmenger syndrome (secondary to a ventriculoseptal defect) who had also undergone contrast-enhanced thin-section CT. CT studies were reviewed for the presence of centrilobular nodules, mosaicism, neovascularity, and bronchial artery hypertrophy. Haemodynamic data were also reviewed. Results: Centrilobular nodules, mosaicism, and neovascularity were seen in both patient groups (p > 0.05). A significantly higher number of enlarged bronchial arteries were seen in patients with Eisenmenger syndrome. There was no correlation with pulmonary arterial pressures. Conclusion: Patients with idiopathic pulmonary arterial hypertension and Eisenmenger syndrome demonstrated similar pulmonary vascular changes on CT. These changes did not predict the underlying cause of pulmonary hypertension or its severity

Eisenmenger syndrome and idiopathic pulmonary arterial hypertension: do parenchymal lung changes reflect aetiology?

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Griffin, N. [Royal Brompton and Harefield NHS Trust, London (United Kingdom)]. E-mail: nyreegriffin@hotmail.com; Allen, D. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Wort, J. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Rubens, M. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Padley, S. [Royal Brompton and Harefield NHS Trust, London (United Kingdom)

2007-06-15

Aim: To document the pulmonary vascular changes on thin-section computed tomography (CT) in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension, and to determine whether there is any correlation with pulmonary arterial pressures or the aetiology of pulmonary hypertension. Material and methods: From the National Pulmonary Hypertension Database, we identified eight patients with idiopathic pulmonary arterial hypertension and 20 patients with Eisenmenger syndrome (secondary to a ventriculoseptal defect) who had also undergone contrast-enhanced thin-section CT. CT studies were reviewed for the presence of centrilobular nodules, mosaicism, neovascularity, and bronchial artery hypertrophy. Haemodynamic data were also reviewed. Results: Centrilobular nodules, mosaicism, and neovascularity were seen in both patient groups (p > 0.05). A significantly higher number of enlarged bronchial arteries were seen in patients with Eisenmenger syndrome. There was no correlation with pulmonary arterial pressures. Conclusion: Patients with idiopathic pulmonary arterial hypertension and Eisenmenger syndrome demonstrated similar pulmonary vascular changes on CT. These changes did not predict the underlying cause of pulmonary hypertension or its severity.

Anomalies of Pulmonary Circulation as a Cause of Hemoptysis: A Series of Unusual Cases and Review of the Literature

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Kamini Gupta

2015-05-01

Full Text Available The expectoration of blood originating from the lower respiratory tract, called hemoptysis, is a common clinical condition with many potential etiologies. Massive hemoptysis is life threatening and needs urgent intervention. Multidetector computed tomography (MDCT is a useful non-invasive imaging modality for the initial assessment of hemoptysis. Using MDCT with multiplanar reformatted images has improved the diagnosis and management of hemoptysis by providing a more precise depiction of bronchial and non-bronchial systemic arteries than conventional computed tomography (CT. In 95% of hemoptysis cases, the systemic arterial system is the origin of bleeding and pulmonary vascular anomalies are a rare cause. Among these, pulmonary arteriovenous malformation, hereditary hemorrhagic telangiectasia, and Osler-Weber-Rendu disease are well known entities. However, primary anomalies affecting pulmonary vessels in the mediastinum or diseases secondarily affecting the pulmonary vessels are unusual causes. Here we present three cases where patients had pulmonary vascular anomalies causing hemoptysis. These patients had decreased pulmonary arterial pressures leading to bronchial and systemic arterial hypertrophy and development of bronchopulmonary collaterals. Secondary CT signs in the parenchyma and mediastinum (mosaic attenuation, ground glass haze, subpleural interstitial thickening, and hypertrophied bronchial arteries were similar in all patients. Hence, evaluation of the MDCT images for primary abnormality led to the diagnosis.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

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Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index, in all postoperative records. For group (II): There were no statistically significant changes between the preoperative and all postoperative records for the central venous pressure, mean arterial pressure and cardiac index. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index in all postoperative records. There were statistically significant changes between the two groups in all postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index. There is right ventricular dysfunction early after major pulmonary resection caused by increased right ventricular afterload. This dysfunction is more present in pneumonectomy than in lobectomy. Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular end diastolic volume index are significantly affected by pulmonary resection.

The effect of altering pulmonary blood flow on pulmonary gas exchange in the turtle Trachemys (Pseudemys) scripta.

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Hopkins, S R; Wang, T; Hicks, J W

1996-10-01

In resting reptiles, the PO2 of pulmonary venous return (PLAO2; left atrial blood) may be 20 mmHg (1 mmHg = 0.1333 kPa) lower than the PO2 of gas in the lung. This level of PO2 is considerably higher than that observed in resting mammals and birds and results from ventilation-perfusion (V/Q) heterogeneity, pulmonary diffusion limitation and intrapulmonary shunting. However, the relative contribution of each of these factors is unknown. Many reptiles, particularly chelonians, exhibit an intermittent ventilation pattern where pulmonary blood flow (QL) increases during the ventilatory periods and, therefore, we hypothesized that V/Q matching would improve with increasing QL. We applied the multiple inert gas elimination technique in anaesthetized turtles at 22 degrees C. Turtles were continuously ventilated at a rate of 140 ml kg-1 min-1, equivalent to the rate of ventilation within a ventilatory period. Trace amounts of six inert gases were infused through the jugular vein. Blood samples from the pulmonary artery and the left atrium and mixed expired gases were collected for analysis. QL was reduced by a factor of six (low flow) using a vascular occluder placed around the common pulmonary artery or increased by a factor of two (high flow) through bolus injection of adrenaline. V/Q heterogeneity was significantly reduced with increasing pulmonary blood flow (P means +/- S.E.M.) and PLAO2 increased significantly (P < 0.05) from 88 +/- 17 mmHg (low flow) to 120 +/- 14 mmHg (high flow). There was evidence of pulmonary diffusion limitation under all conditions, which was unchanged with increasing blood flow. These findings suggest that increased pulmonary blood flow during a ventilatory period results in both temporal and spatial matching of ventilation and perfusion, without altering pulmonary diffusion limitation.

Pulmonary Hypertension in the Intensive Care Unit.

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Jentzer, Jacob C; Mathier, Michael A

2016-07-01

Pulmonary hypertension occurs as the result of disease processes increasing pressure within the pulmonary circulation, eventually leading to right ventricular failure. Patients may become critically ill from complications of pulmonary hypertension and right ventricular failure or may develop pulmonary hypertension as the result of critical illness. Diagnostic testing should evaluate for common causes such as left heart failure, hypoxemic lung disease and pulmonary embolism. Relatively few patients with pulmonary hypertension encountered in clinical practice require specific pharmacologic treatment of pulmonary hypertension targeting the pulmonary vasculature. Management of right ventricular failure involves optimization of preload, maintenance of systemic blood pressure and augmentation of inotropy to restore systemic perfusion. Selected patients may require pharmacologic therapy to reduce right ventricular afterload by directly targeting the pulmonary vasculature, but only after excluding elevated left heart filling pressures and confirming increased pulmonary vascular resistance. Critically-ill patients with pulmonary hypertension remain at high risk of adverse outcomes, requiring a diligent and thoughtful approach to diagnosis and treatment. © The Author(s) 2015.

Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

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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

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

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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.

Pulmonary phenotypes associated with genetic variation in telomere-related genes.

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Hoffman, Thijs W; van Moorsel, Coline H M; Borie, Raphael; Crestani, Bruno

2018-05-01

Genomic mutations in telomere-related genes have been recognized as a cause of familial forms of idiopathic pulmonary fibrosis (IPF). However, it has become increasingly clear that telomere syndromes and telomere shortening are associated with various types of pulmonary disease. Additionally, it was found that also single nucleotide polymorphisms (SNPs) in telomere-related genes are risk factors for the development of pulmonary disease. This review focuses on recent updates on pulmonary phenotypes associated with genetic variation in telomere-related genes. Genomic mutations in seven telomere-related genes cause pulmonary disease. Pulmonary phenotypes associated with these mutations range from many forms of pulmonary fibrosis to emphysema and pulmonary vascular disease. Telomere-related mutations account for up to 10% of sporadic IPF, 25% of familial IPF, 10% of connective-tissue disease-associated interstitial lung disease, and 1% of COPD. Mixed disease forms have also been found. Furthermore, SNPs in TERT, TERC, OBFC1, and RTEL1, as well as short telomere length, have been associated with several pulmonary diseases. Treatment of pulmonary disease caused by telomere-related gene variation is currently based on disease diagnosis and not on the underlying cause. Pulmonary phenotypes found in carriers of telomere-related gene mutations and SNPs are primarily pulmonary fibrosis, sometimes emphysema and rarely pulmonary vascular disease. Genotype-phenotype relations are weak, suggesting that environmental factors and genetic background of patients determine disease phenotypes to a large degree. A disease model is presented wherever genomic variation in telomere-related genes cause specific pulmonary disease phenotypes whenever triggered by environmental exposure, comorbidity, or unknown factors.

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

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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.

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

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Sugimoto, Koichi; Yoshihisa, Akiomi; Nakazato, Kazuhiko; Jin, Yuichiro; Suzuki, Satoshi; Yokokawa, Tetsuro; Misaka, Tomofumi; Yamaki, Takayoshi; Kunii, Hiroyuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2016-01-01

Background 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. Methods 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. Results 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). Conclusion PAC is useful in the prediction of cardiac event risk in LHD-PH patients. PMID:27875533

Pulmonary langerhans cell histiocytosis

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Suri Harpreet S

2012-03-01

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

Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil.

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Snow, Samantha J; Cheng, Wan-Yun; Henriquez, Andres; Hodge, Myles; Bass, Virgina; Nelson, Gail M; Carswell, Gleta; Richards, Judy E; Schladweiler, Mette C; Ledbetter, Allen D; Chorley, Brian; Gowdy, Kymberly M; Tong, Haiyan; Kodavanti, Urmila P

2018-05-01

Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.

Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs.

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Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L; Parker, Thomas A; Abman, Steven H

2004-01-01

Endothelin-1 (ET-1) contributes to the regulation of pulmonary vascular tone in the normal ovine fetus and in models of perinatal pulmonary hypertension. In the fetal lamb lung, the effects of ET-1 depend on the balance of at least two endothelin receptor subtypes: ETA and ETB. ETA receptors are located on smooth muscle cells and mediate vasoconstriction and smooth muscle proliferation. Stimulation of endothelial ETB receptors causes vasodilation through release of nitric oxide and also functions to remove ET-1 from the circulation. However, whether activation of ETB receptors contributes to the fall in pulmonary vascular tone at birth is unknown. To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep. Intrapulmonary infusion of BQ-788 did not change left pulmonary artery (LPA) blood flow and pulmonary vascular resistance (PVR) at baseline. In comparison with controls, BQ-788 treatment attenuated the rise in LPA flow with low and high FiO2 ventilation (p <0.001 vs. control for each FiO2 concentration). PVR progressively decreased during mechanical ventilation with low and high FiO2 in both groups, but PVR remained higher after BQ-788 treatment throughout the study period (p <0.001). We conclude that selective ETB receptor blockade attenuates pulmonary vasodilation at birth. We speculate that ETB receptor stimulation contributes to pulmonary vasodilation at birth in the ovine fetus.

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

NARCIS (Netherlands)

B. Houweling (Birgit)

2007-01-01

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

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

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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

Research on a Pulmonary Nodule Segmentation Method Combining Fast Self-Adaptive FCM and Classification

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Hui Liu

2015-01-01

Full Text Available The key problem of computer-aided diagnosis (CAD of lung cancer is to segment pathologically changed tissues fast and accurately. As pulmonary nodules are potential manifestation of lung cancer, we propose a fast and self-adaptive pulmonary nodules segmentation method based on a combination of FCM clustering and classification learning. The enhanced spatial function considers contributions to fuzzy membership from both the grayscale similarity between central pixels and single neighboring pixels and the spatial similarity between central pixels and neighborhood and improves effectively the convergence rate and self-adaptivity of the algorithm. Experimental results show that the proposed method can achieve more accurate segmentation of vascular adhesion, pleural adhesion, and ground glass opacity (GGO pulmonary nodules than other typical algorithms.

A continuum model for pressure-flow relationship in human pulmonary circulation.

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Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

2011-06-01

A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation.

Radiographic findings in pulmonary hypertension from unresolved embolism

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Woodruff, W.W. III; Hoeck, B.E.; Chitwood, W.R. Jr.; Lyerly, H.K.; Sabiston, D.C. Jr.; Chen, J.T.T.

1985-04-01

Pulmonary artery hypertension with chronic pulmonary embolism is an uncommon entity that is potentially treatable with pulmonary embolectomy. Although the classic radiographic features have been described, several recent investigators report a significant percentage of these patients with normal chest radiographs. In a series of 22 patients, no normal radiographs were seen. Findings included cardiomegaly (86.4%) with right-sided enlargement (68.4%), right descending pulmonary artery enlargement (54.5%), azygos vein enlargement (27.3%), mosaic oligemia (68.2%), chronic volume loss (27.3%), atelectasis and/or effusion (22.7%), and pleural thickening (13.6%). Good correlation with specific areas of diminished vascularity was seen on chest radiographs compared with pulmonary angiograms.

Radiographic findings in pulmonary hypertension from unresolved embolism

International Nuclear Information System (INIS)

Woodruff, W.W. III; Hoeck, B.E.; Chitwood, W.R. Jr.; Lyerly, H.K.; Sabiston, D.C. Jr.; Chen, J.T.T.

1985-01-01

Pulmonary artery hypertension with chronic pulmonary embolism is an uncommon entity that is potentially treatable with pulmonary embolectomy. Although the classic radiographic features have been described, several recent investigators report a significant percentage of these patients with normal chest radiographs. In a series of 22 patients, no normal radiographs were seen. Findings included cardiomegaly (86.4%) with right-sided enlargement (68.4%), right descending pulmonary artery enlargement (54.5%), azygos vein enlargement (27.3%), mosaic oligemia (68.2%), chronic volume loss (27.3%), atelectasis and/or effusion (22.7%), and pleural thickening (13.6%). Good correlation with specific areas of diminished vascularity was seen on chest radiographs compared with pulmonary angiograms

The clinical presentation of pulmonary embolism

International Nuclear Information System (INIS)

Otto, A.C.; Dunn, M.; Van der Merwe, B.; Katz, M.

2004-01-01

Full text: Introduction: Pulmonary embolism is often misdiagnosed by many clinicians because of confusion with pulmonary infarction. According to present literature, the latter seldomly occurs, thus pleuritic pain and hemoptysis are usually absent. The purpose of our study was to re-evaluate the clinical presentation of pulmonary embolism with specific reference to the presence of pulmonary hypertension and pulmonary infarction. Materials and methods: Ethical committee approval was obtained to study fifteen patients with abnormal lung perfusion and high probability for pulmonary embolism retrospectively. Clinical data will be presented in table format. Appropriate symptoms and signs not mentioned was considered absent. Specific investigations not available was considered not done. Results: Will be displayed in table format. The main findings can be summarized as follows: 1. Dyspnea was present in all the patients; 2. Pleuritic pain and hemoptysis was absent in all the patients; 3. None of the patients had clinical signs of pulmonary hypertension or infarction; 4. The available special investigations confirmed the above mentioned findings. Conclusion: The absence of pulmonary infarction and pulmonary hypertension with submassive pulmonary embolism (<60% of pulmonary vascular bed occluded) was reconfirmed and should be emphasized more in clinical practice. (author)

Contemporary Management of Pulmonary Arteriovenous Malformations.

Science.gov (United States)

Rauh, Nicholas; Gurley, John; Saha, Sibu

2017-12-01

Pulmonary arteriovenous malformations (PAVMs) are atypical vascular structures involving a direct connection between the pulmonary arterial and venous circulations. While PAVMs are a relatively uncommon disorder, unmanaged cases are at risk for the development of serious complications including embolization and infection. Since their first description in 1897, PAVMs have been identified and treated in a variety of ways. Advancements in diagnostic methods and operative techniques have allowed for more effective treatment of the disease. Most recently, the use of vascular plug transcatheter embolization has been described as an effective therapeutic procedure in the management of PAVMs. In this report, we present our experience with nine cases of PAVMs treated at the University of Kentucky, including special consideration of an exemplary case that illustrates the typical course of treatment for the disease.

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

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Adel Boueiz

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1996-09-01

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

Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM?) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

OpenAIRE

Angelini, Daniel J.; Su, Qingning; Kolosova, Irina A.; Fan, Chunling; Skinner, John T.; Yamaji-Kegan, Kazuyo; Collector, Michael; Sharkis, Saul J.; Johns, Roger A.

2010-01-01

Background Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling ...

Ketamine and Pulmonary Oedema-Report of Two Cases

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S Parthasarathy

2009-01-01

Full Text Available Perioperative pulmonary oedema is one of the most challenging complications faced by anaesthesiologists. In most of the instances, coronary artery disease, valvular heart diseases, hypertension may precipitate pulmonary oedema due to increased hydrostatic pressure while acid aspiration, airway obstruction may cause it due to increased vascular permeability. In a few instances, acute pulmonary oedema can present in an otherwise healthy patient to cause diagnostic difficulties. We report two such cases of intra operative pulmonary oedema with the use of ketamine which were identified and managed successfully. The most probable cause is also described.

Importance of absent ductus arteriosus in tetralogy of Fallot with absent pulmonary valve syndrome.

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Qureshi, Muhammad Yasir; Burkhart, Harold M; Julsrud, Paul; Cetta, Frank

2014-12-01

Tetralogy of Fallot without pulmonary valve syndrome is almost always associated with an absent ductus arteriosus. Patients with right aortic arch and retroesophageal left subclavian artery have a vascular ring if the left ductus arteriosus or its remnant and the Kommerell diverticulum are present. We report the cases of 2 infants in whom the role of an absent ductus arteriosus or its remnant is noteworthy. Both patients had a combination of tetralogy of Fallot with absent pulmonary valve syndrome and right aortic arch with retroesophageal left subclavian artery without a vascular ring. The absence of the ductus arteriosus has a role in the pathogenesis of tetralogy of Fallot with absent pulmonary valve syndrome. The absence of a ductus arteriosus in the right aortic arch with retroesophageal left subclavian artery precludes a vascular ring.

Pulmonary thromboembolism in children

Energy Technology Data Exchange (ETDEWEB)

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

2005-03-01

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

Pulmonary thromboembolism in children

International Nuclear Information System (INIS)

Babyn, Paul S.; Gahunia, Harpal K.; Massicotte, Patricia

2005-01-01

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

Correlation of grading of pulmonary emphysema by computed tomography to pulmonary function

International Nuclear Information System (INIS)

Yamagishi, Masahiko; Mori, Masaki; Hirai, Hideyuki; Mori, Yuji; Koba, Hiroyuki; Suzuki, Akira

1988-01-01

We studied the CT findings of 17 emphysema patients with special reference to the extent of emphysematous changes. Characteristic CT findings were low-attenuation area (LAA) and vascular abnormality and the appearance of various images on CT. To assess the extent of emphysematous changes, we classified the CT images into 4 grades based on the distribution and size of LAAs. As the grades progressed, the distribution and size of LAAs became wider and larger and vascular abnormalities were clearly evident. Although this CT-grading is a semiquantitative method, it is simple to use and gives information on the approximate extent of disease. This CT-grading was also used to show pulmonary function. The RV/TLC and expiratory flow showed a tendency to be impaired in Grade IV and the diffusion capacity was impaired parallel to CT-grading. CT is able to demonstrate the presence and distribution of LAAs noninvasively. Therefore it is considered that CT is useful for clinical diagnosis and the assessment of the extent of pulmonary emphysema. (author)

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

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Ulisses Alexandre Croti

2005-01-01

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

Mycotic pulmonary artery aneurysm as an unusual complication of thoracic actinomycosis

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Kim, Hyung-Soo; Lee, Sang-Yeub [Wonkwang University College, Iksan (Korea, Republic of); Oh, Yu-Whan; Noh, Hyung-Jun; Lee, Ki-Yeol; Kang, Eun-Young [Korea University Hospital and Korea University College, Seoul (Korea, Republic of)

2004-03-15

Although pulmonary artery aneurysms are a rare vascular anomaly, they are seen in a wide variety of conditions, such as congenital heart disease, infection, trauma, pulmonary hypertension, cystic medial necrosis and generalized vasculitis. To our knowledge, mycotic aneurysms caused by pulmonary actinomycosis have not been reported in the radiologic literature. Herein, a case of pulmonary actinomycosis complicated by mycotic aneurysm is presented. On CT scans, this case showed focal aneurysmal dilatation of a peripheral pulmonary artery within necrotizing pneumonia of the right lower lobe, which was successfully treated with transcatheter embolization using wire coils.

Mycotic pulmonary artery aneurysm as an unusual complication of thoracic actinomycosis

International Nuclear Information System (INIS)

Kim, Hyung-Soo; Lee, Sang-Yeub; Oh, Yu-Whan; Noh, Hyung-Jun; Lee, Ki-Yeol; Kang, Eun-Young

2004-01-01

Although pulmonary artery aneurysms are a rare vascular anomaly, they are seen in a wide variety of conditions, such as congenital heart disease, infection, trauma, pulmonary hypertension, cystic medial necrosis and generalized vasculitis. To our knowledge, mycotic aneurysms caused by pulmonary actinomycosis have not been reported in the radiologic literature. Herein, a case of pulmonary actinomycosis complicated by mycotic aneurysm is presented. On CT scans, this case showed focal aneurysmal dilatation of a peripheral pulmonary artery within necrotizing pneumonia of the right lower lobe, which was successfully treated with transcatheter embolization using wire coils

The brain in hereditary hemorrhagic telangiectasia with pulmonary AVM: The clinical importance of paradoxical embolism

International Nuclear Information System (INIS)

Kim, W.S.; Kinnison, M.L.; Charnas, L.; Rosenbaum, A.E.; White, R.I. Jr.

1986-01-01

Despite the literature's emphasis on the presence of intracerebral vascular malformations in hereditary hemorrhagic telangiectasia (HHT), few cases have been documented. The authors prospectively evaluated brain CT scans in 29 consecutive patients with pulmonary arteriovenous malformations (AVMs) and known HHT. Fifty-five percent of the CT scans revealed the signs of embolic phenomena: infarctions (n=11) and intracerebral abscesses (n=5). In only one patient was a small enhancing vascular lesion seen. They conclude that embolic phenomena rather than vascular malformations cause the majority of abnormal CT findings in patients with HHT and pulmonary AVMs. Infarctions and intracerebral abscesses probably result from paradoxical embolization through the AVMs in the lungs. The therapeutic implications seem clear, since 55% of these patients are potentially treatable by balloon occlusion of the pulmonary AVMs

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

Science.gov (United States)

He, Hong-Jun; Dai, Ai-Guo

2012-05-01

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

Pulmonary Hypertension in Pregnancy: Critical Care Management

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Adel M. Bassily-Marcus

2012-01-01

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

Hypoxia Inducible Factor Signaling and Experimental Persistent Pulmonary Hypertension of the Newborn: A Therapeutic Opportunity

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Stephen eWedgwood

2015-03-01

Full Text Available BACKGROUND: Mitochondrial reactive oxygen species levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB activity are increased in a lamb model of persistent pulmonary hypertension of the newborn (PPHN. These events can trigger hypoxia inducible factor (HIF signaling in response to hypoxia, which has been shown to contribute to pulmonary vascular remodeling in rodent models of pulmonary hypertension. However the role of HIF signaling in chronic intrauterine pulmonary hypertension is not well understood.AIM: To determine if HIF signaling is increased in the lamb model of PPHN, and to identify the underlying mechanisms. RESULTS: PPHN was induced in lambs by antenatal ligation of the ductus arteriosus at 128 days gestation. After 9 days, lungs and pulmonary artery smooth muscle cells (PASMC were isolated from control and PPHN lambs. HIF-1α expression was increased in PPHN lungs and HIF activity was increased in PPHN PASMC relative to controls. Hypoxia increased HIF activity to a greater degree in PPHN vs. control PASMC. Control PASMC were exposed to cyclic stretch at 1Hz and 15% elongation for 24h, as an in vitro model of vascular stress. Stretch increased HIF activity, which was attenuated by inhibition of mitochondrial complex III and NFκB.CONCLUSION: Increased HIF signaling in PPHN is triggered by stretch, via mechanisms involving mitochondrial ROS and NFκB. Hypoxia substantially amplifies HIF activity in PPHN vascular cells. Targeting these signaling molecules may attenuate and reverse pulmonary vascular remodeling associated with PPHN.

Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

LENUS (Irish Health Repository)

Sands, Michelle

2011-01-25

Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

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

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

ACTIVITIES RESULTS AIMED AT IMPROVED MEDICAL ASSISTANCE TO THE VASCULAR PATIENTS IN TOMSK REGION

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D. M. Plotnikov

2013-01-01

Full Text Available Acute disorders of cerebral circulation remain serious medical and social problem associated with high disability and mortality rates. Since 2011 Tomsk oblast is a participating member of the medical campaign aimed at improved medical services to the vascular patients. The preliminary implementation data analysis for 2012 revealed improvement of most of the indices of medical support to patients suffering from acute cerebral circulation; increased number of the in-patient cases (Regional Vascular Center and primary vascular department, decreased lethality rates from strokes, specifically hemorrhagic cases. Strict observance of the Regulations on Medical Assistance for stroke patients and the using of modern methods of therapy allowed to decrease hospital mortality in the Primary Vascular Departments and early mortality in the Regional Vascular Center. The active implementation of neurorehabilitation approaches resulted in the increased number of patients who do not require third parties’ assistance. Analysis of the work of the departments helped to identifying current problems and perspectives of further development of special medical care for stroke patients.

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

Science.gov (United States)

Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

2017-01-01

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, despite a

Pulmonary gangrene as a complication of mucormycosis

International Nuclear Information System (INIS)

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

1985-01-01

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

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...

Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine.

LENUS (Irish Health Repository)

McCaul, Conán

2009-10-01

Multiple interventions have been tested in models of cardiopulmonary resuscitation (CPR) to optimize drug use, chest compressions, and ventilation. None has studied the effects of positive end-expiratory pressure (PEEP) on outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis, lower pulmonary vascular resistance, and potentially improve cardiac output, its use during CPR would increase survival.

Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

Science.gov (United States)

Roy Chaudhuri, Tista

An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

Usefulness of semiquantitative analysis of dipyridamole-thallium-201 redistribution for improving risk stratification before vascular surgery

International Nuclear Information System (INIS)

Levinson, J.R.; Boucher, C.A.; Coley, C.M.; Guiney, T.E.; Strauss, H.W.; Eagle, K.A.

1990-01-01

Preoperative dipyridamole-thallium-201 scanning is sensitive in identifying patients prone to ischemic cardiac complications after vascular surgery, but most patients with redistribution do not have an event after surgery. Therefore, its positive predictive value is limited. To determine which patients with thallium redistribution are at highest risk, dipyridamole-thallium-201 images were interpreted semiquantitatively. Sixty-two consecutive patients with redistribution on preoperative dipyridamole-thallium-201 planar imaging studies were identified. Each thallium scan was then analyzed independently by 2 observers for the number of myocardial segments out of 15, the number of thallium views out of 3 and the number of coronary artery territories with redistribution. Seventeen patients (27%) had postoperative ischemic events, including unstable angina pectoris, ischemic pulmonary edema, myocardial infarction and cardiac death. Thallium predictors of ischemic operative complications included thallium redistribution greater than or equal to 4 myocardial segments (p = 0.03), greater than or equal to 2 of the 3 planar views (p = 0.005) and greater than or equal to 2 coronary territories (p = 0.007). No patient with redistribution in only 1 view had an ischemic event (0 of 15). Thus, determining the extent of redistribution by dipyridamole-thallium-201 scanning improves risk stratification before vascular surgery. Patients with greater numbers of myocardial segments and greater numbers of coronary territories showing thallium-201 redistribution are at higher risk for ischemic cardiac complications. In contrast, when the extent of thallium redistribution is limited, there is a lower risk despite the presence of redistribution

Computed tomography in the detection of pulmonary metastases. Improvement by application of spiral technology

International Nuclear Information System (INIS)

Kauczor, H.U.; Hansen, M.; Schweden, F.; Strunk, H.; Mildenberger, P.; Thelen, M.

1994-01-01

Computed tomography is the imaging modality of choice for detection or exclusion of pulmonary metastases. In most cases these are spheric, multiple, bilateral, and located in the peripheral areas of the middle and lower fields of the lungs. Differential diagnosis of solitary pulmonary nodules is difficult. Evaluating whether they are malignant or benign is insufficient despite the application of multiple CT criteria. Spiral computed tomography acquiring an imaging volume in a breathhold has led to significant improvement in the sensitivity of detecting pulmonary nodules. Imaging protocols are presented, and the influence of the different parameters is discussed. Although not all pulmonary metastases may be detected with spiral computed tomography, it is the most important examination when considering pulmonary metastasectomy. Computed tomography is the imaging modality of choice when monitoring pulmonary metastases during systemic therapeutic regimens by measuring all nodules or 'indicator lesions'. (orig.) [de

Radiological aspects in pulmonary involvement of Behcet disease

International Nuclear Information System (INIS)

Kim, Jae Hyoung; Im, Jung Gi; Kim, Hyung Jin; Park, Jae Hyung

1988-01-01

To evaluate the pulmonary manifestations of Behcet disease, authors reviewed the chest radiographs of 130 cases of Behcet disease diagnosed at Seoul National University Hospital from January 1980 to December 1987 retrospectively. Of the 130 cases, 6 cases (4.6%) showed pulmonary abnormalities that were considered as a manifestation of Behcet disease. Two cases showed round masses near the hila on chest radiographs which were confirmed as pulmonary artery aneurysms on angiographies. Two cases showed pulmonary infiltrates due to pulmonary infarcts. Others were a case of unilateral pulmonary edema due to compression og the contralateral pulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a compulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a complication of esophageal ulcer. Though its occurrence is rare, nodular and/or infiltrative pulmonary lesions in patients with Behcet disease should be suspected as a vascular involvement of the disease itself until proven otherwise.

Radiological aspects in pulmonary involvement of Behcet disease

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Hyoung; Im, Jung Gi; Kim, Hyung Jin; Park, Jae Hyung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1988-08-15

To evaluate the pulmonary manifestations of Behcet disease, authors reviewed the chest radiographs of 130 cases of Behcet disease diagnosed at Seoul National University Hospital from January 1980 to December 1987 retrospectively. Of the 130 cases, 6 cases (4.6%) showed pulmonary abnormalities that were considered as a manifestation of Behcet disease. Two cases showed round masses near the hila on chest radiographs which were confirmed as pulmonary artery aneurysms on angiographies. Two cases showed pulmonary infiltrates due to pulmonary infarcts. Others were a case of unilateral pulmonary edema due to compression og the contralateral pulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a compulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a complication of esophageal ulcer. Though its occurrence is rare, nodular and/or infiltrative pulmonary lesions in patients with Behcet disease should be suspected as a vascular involvement of the disease itself until proven otherwise.

Improved diagnosis of pulmonary emphysema using in vivo dark-field radiography.

Science.gov (United States)

Meinel, Felix G; Yaroshenko, Andre; Hellbach, Katharina; Bech, Martin; Müller, Mark; Velroyen, Astrid; Bamberg, Fabian; Eickelberg, Oliver; Nikolaou, Konstantin; Reiser, Maximilian F; Pfeiffer, Franz; Yildirim, Ali Ö

2014-10-01

The purpose of this study was to assess whether the recently developed method of grating-based x-ray dark-field radiography can improve the diagnosis of pulmonary emphysema in vivo. Pulmonary emphysema was induced in female C57BL/6N mice using endotracheal instillation of porcine pancreatic elastase and confirmed by in vivo pulmonary function tests, histopathology, and quantitative morphometry. The mice were anesthetized but breathing freely during imaging. Experiments were performed using a prototype small-animal x-ray dark-field scanner that was operated at 35 kilovolt (peak) with an exposure time of 5 seconds for each of the 10 grating steps. Images were compared visually. For quantitative comparison of signal characteristics, regions of interest were placed in the upper, middle, and lower zones of each lung. Receiver-operating-characteristic statistics were performed to compare the effectiveness of transmission and dark-field signal intensities and the combined parameter "normalized scatter" to differentiate between healthy and emphysematous lungs. A clear visual difference between healthy and emphysematous mice was found for the dark-field images. Quantitative measurements of x-ray dark-field signal and normalized scatter were significantly different between the mice with pulmonary emphysema and the control mice and showed good agreement with pulmonary function tests and quantitative histology. The normalized scatter showed a significantly higher discriminatory power (area under the receiver-operating-characteristic curve [AUC], 0.99) than dark-field (AUC, 0.90; P = 0.01) or transmission signal (AUC, 0.69; P pulmonary emphysema.

Pulmonary hypertension due to left heart disease.

Science.gov (United States)

Berthelot, Emmanuelle; Bailly, Minh Tam; Hatimi, Safwane El; Robard, Ingrid; Rezgui, Hatem; Bouchachi, Amir; Montani, David; Sitbon, Olivier; Chemla, Denis; Assayag, Patrick

Pulmonary hypertension due to left heart disease, also known as group 2 pulmonary hypertension according to the European Society of Cardiology/European Respiratory Society classification, is the most common cause of pulmonary hypertension. In patients with left heart disease, the development of pulmonary hypertension favours right heart dysfunction, which has a major impact on disease severity and outcome. Over the past few years, this condition has been considered more frequently. However, epidemiological studies of group 2 pulmonary hypertension are less exhaustive than studies of other causes of pulmonary hypertension. In group 2 patients, pulmonary hypertension may be caused by an isolated increase in left-sided filling pressures or by a combination of this condition with increased pulmonary vascular resistance, with an abnormally high pressure gradient between arteries and pulmonary veins. A better understanding of the conditions underlying pulmonary hypertension is of key importance to establish a comprehensive diagnosis, leading to an adapted treatment to reduce heart failure morbidity and mortality. In this review, epidemiology, mechanisms and diagnostic approaches are reviewed; then, treatment options and future approaches are considered. Copyright © 2017. Published by Elsevier Masson SAS.

Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat.

Science.gov (United States)

Doherty, R E; Aviado, D M

1975-01-01

Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.

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

Directory of Open Access Journals (Sweden)

de Matthaeis A

2014-05-01

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

Advanced virtual monoenergetic images: improving the contrast of dual-energy CT pulmonary angiography

International Nuclear Information System (INIS)

Meier, A.; Wurnig, M.; Desbiolles, L.; Leschka, S.; Frauenfelder, T.; Alkadhi, H.

2015-01-01

Aim: To investigate the value of advanced virtual monoenergetic image reconstruction (mono-plus) from dual-energy computed tomography (CT) for improving the contrast of CT pulmonary angiography (CTPA). Materials and methods: Forty consecutive patients (25 women, mean 62.5 years, range 28–87 years) underwent 192-section dual-source CTPA with dual-energy CT (90/150 SnkVp) after the administration of 60 ml contrast media (300 mg iodine/ml). Conventional virtual monochromatic images at 60 keV and 17 mono-plus image datasets from 40–190 keV (in 10 keV steps) were reconstructed. Subjective image quality (artefacts, subjective noise) was rated. Attenuation was measured in the pulmonary trunk and in the right lower lobe pulmonary artery; noise was measured in the periscapular musculature. The signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were calculated for each patient and dataset. Comparisons between monochromatic images and mono-plus images were performed by repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction. Results: Interreader agreement was good to excellent for subjective image quality (ICC: 0.616–0.889). As compared to conventional 60 keV images, artefacts occurred less (p=0.001) and subjective noise was rated lower (p<0.001) in mono-plus 40 keV images. Noise was lower (p<0.001), and the SNR and CNR in the pulmonary trunk and right lower lobe pulmonary artery were higher (both, p<0.001) in mono-plus 40 keV images compared to conventional monoenergetic 60 keV images. Transient interruption of contrast (TIC) was found in 14/40 (35%) of patients, with subjective contrast being similar 8/40 (20%) or higher 32/40 (80%) in mono-plus 40 keV as compared to conventional monoenergetic 60 keV images. Conclusions: Compared to conventional virtual monoenergetic imaging, mono-plus images at 40 keV improve the contrast of dual-energy CTPA. - Highlights: • Advanced monoenergetic image reconstruction from dual-energy CT

Radioaerosol inhalation lung imaging for the diagnosis of chronic obstructive pulmonary diseases in Thailand. Final report for the period 10 December 1987 - 15 December 1993

Energy Technology Data Exchange (ETDEWEB)

Buachum, V [Chulalongkorn Univ., Bangkok (Thailand). Nuclear Medicine Div.

1993-12-01

The radionuclide pulmonary function studies such as aerosol inhalation lung imaging, mucociliary clearance and pulmonary epithelial were developed and studied in normal and chronic obstructive pulmonary disease. The results of the aerosol inhalation lung imaging in 71 cases of COPD revealed that the aerosol inhalation lung scan was the most sensitive test for the diagnosis of early COPD as compared to the chest X-ray, vascular perfusion lung scan and spirometric test (% FEVI). The aerosol and perfusion lung scan were also performed in 21 cases of carcinoma of lung who had been treated with external radiation or chemotherapy. The result of study revealed 5 patients died during treatment, 5 patients were slightly improved, no significant change was detected in 10 cases and deterioration was found in one patient. The lung scintigraphy was studied in 15 cases of well differentiated carcinoma of thyroid with pulmonary metastasis who had I-131 treatment. The study showed that the radioactive iodine treatment dose had minimal effect on the post treatment lung imaging study. The perfusion and aerosol study in 15 cases of operated patients revealed no evidence of pulmonary embolism in post operative study. Abnormal vascular disease or pulmonary embolism was observed in one patient preoperatively. 12 refs, 13 figs, 13 tabs.

Radioaerosol inhalation lung imaging for the diagnosis of chronic obstructive pulmonary diseases in Thailand. Final report for the period 10 December 1987 - 15 December 1993

International Nuclear Information System (INIS)

Buachum, V.

1993-12-01

The radionuclide pulmonary function studies such as aerosol inhalation lung imaging, mucociliary clearance and pulmonary epithelial were developed and studied in normal and chronic obstructive pulmonary disease. The results of the aerosol inhalation lung imaging in 71 cases of COPD revealed that the aerosol inhalation lung scan was the most sensitive test for the diagnosis of early COPD as compared to the chest X-ray, vascular perfusion lung scan and spirometric test (% FEVI). The aerosol and perfusion lung scan were also performed in 21 cases of carcinoma of lung who had been treated with external radiation or chemotherapy. The result of study revealed 5 patients died during treatment, 5 patients were slightly improved, no significant change was detected in 10 cases and deterioration was found in one patient. The lung scintigraphy was studied in 15 cases of well differentiated carcinoma of thyroid with pulmonary metastasis who had I-131 treatment. The study showed that the radioactive iodine treatment dose had minimal effect on the post treatment lung imaging study. The perfusion and aerosol study in 15 cases of operated patients revealed no evidence of pulmonary embolism in post operative study. Abnormal vascular disease or pulmonary embolism was observed in one patient preoperatively. 12 refs, 13 figs, 13 tabs

Determinants of pulmonary blood flow distribution.

Science.gov (United States)

Glenny, Robb W; Robertson, H Thomas

2011-01-01

The primary function of the pulmonary circulation is to deliver blood to the alveolar capillaries to exchange gases. Distributing blood over a vast surface area facilitates gas exchange, yet the pulmonary vascular tree must be constrained to fit within the thoracic cavity. In addition, pressures must remain low within the circulatory system to protect the thin alveolar capillary membranes that allow efficient gas exchange. The pulmonary circulation is engineered for these unique requirements and in turn these special attributes affect the spatial distribution of blood flow. As the largest organ in the body, the physical characteristics of the lung vary regionally, influencing the spatial distribution on large-, moderate-, and small-scale levels. © 2011 American Physiological Society.

From here to there, progenitor cells and stem cells are everywhere in lung vascular remodeling

Directory of Open Access Journals (Sweden)

Rebecca L. Heise

2016-08-01

Full Text Available The field of stem cell biology, cell therapy and regenerative medicine has expanded almost exponentially in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD, chronic obstructive pulmonary disease (COPD, idiopathic pulmonary fibrosis (IPF or pulmonary arterial hypertension (PAH. Extensive research activity is exploring lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field.

High resolution CT in pulmonary sarcoidosis

International Nuclear Information System (INIS)

Spina, Juan C.; Curros, Marisela L.; Gomez, M.; Gonzalez, A.; Chacon, Carolina; Guerendiain, G.

2000-01-01

Objectives: To establish the particular advantages of High Resolution CT (HRCT) for the diagnosis of pulmonary sarcoidosis. Material and Methods: A series of fourteen patients, (4 men and 10 women; mean age 44,5 years) with thoracic sarcoidosis. All patients were studied using HRCT and diagnosis was confirmed for each case. Confidence intervals were obtained for different disease manifestations. Results: The most common findings were: lymph node enlargement (n=14 patients), pulmonary nodules (n=13), thickening of septa (n=6), peribronquial vascular thickening (n=5) pulmonary pseudo mass (n=5) and signs of fibrosis (n=4). The stage most commonly observed was stage II. It is worth noting that no cases of pleural effusion or cavitations of pulmonary lesions were observed. Conclusions: In this series, confidence interval overlapping for lymph node enlargement, single pulmonary nodules and septum thickening, allows to infer that their presence in a young adult, with few clinical symptoms, forces to rule out first the possibility of sarcoidosis. (author)

Lung infarction following pulmonary embolism. A comparative study on clinical conditions and CT findings to identify predisposing factors

Energy Technology Data Exchange (ETDEWEB)

Kirchner, J.; Obermann, A.; Stueckradt, S.; Tueshaus, C. [General Hospital Hagen (Germany). Radiology; Goltz, J.; Kickuth, R. [University Hospital Wuerzburg (Germany). Radiology; Liermann, D. [University Hospital Marienhospital Herne (Germany). Radiology

2015-06-15

The aim of this study was to identify factors predisposing to lung infarction in patients with pulmonary embolism (PE). We performed a retrospective analysis on 154 patients with the final diagnosis of PE being examined between January 2009 and December 2012 by means of a Toshiba Aquilion 64 CT scanner. The severity of clinical symptoms was defined by means of a clinical index with 4 classes. The pulmonary clot load was quantified using a modified severity index of PE as proposed by Miller. We correlated several potential predictors of pulmonary infarction such as demographic data, pulmonary clot burden, distance of total vascular obstruction and pleura, the presence of cardiac congestion, signs of chronic bronchitis or emphysema with the occurrence of pulmonary infarction. Computed tomography revealed 78 areas of pulmonary infarction in 45/154 (29.2%) patients. The presence of infarction was significantly higher in the right lung than in the left lung (p < 0.001). We found no correlation between pulmonary infarction and the presence of accompanying malignant diseases (r=-0.069), signs of chronic bronchitis (r=-0.109), cardiac congestion (r=-0.076), the quantified clot burden score (r=0.176), and the severity of symptoms (r=-0.024). Only a very weak negative correlation between the presence of infarction and age (r=-0.199) was seen. However, we could demonstrate a moderate negative correlation between the distance of total vascular occlusion and the occurrence of infarction (r=-0.504). Neither cardiac congestion nor the degree of pulmonary vascular obstruction are main factors predisposing to pulmonary infarction in patients with PE. It seems that a peripheral total vascular obstruction more often results in infarction than even massive central clot burden.

Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition.

Science.gov (United States)

Suzuki, Toshio; Tada, Yuji; Gladson, Santhi; Nishimura, Rintaro; Shimomura, Iwao; Karasawa, Satoshi; Tatsumi, Koichiro; West, James

2017-10-16

Pulmonary fibrosis is a late manifestation of acute respiratory distress syndrome (ARDS). Sepsis is a major cause of ARDS, and its pathogenesis includes endotoxin-induced vascular injury. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play an important role in pulmonary fibrosis. On the other hand, dipeptidyl peptidase (DPP)-4 was reported to improve vascular dysfunction in an experimental sepsis model, although whether DPP-4 affects EndMT and fibrosis initiation during lipopolysaccharide (LPS)-induced lung injury is unclear. The aim of this study was to investigate the anti-EndMT effects of the DPP-4 inhibitor vildagliptin in pulmonary fibrosis after systemic endotoxemic injury. A septic lung injury model was established by intraperitoneal injection of lipopolysaccharide (LPS) in eight-week-old male mice (5 mg/kg for five consecutive days). The mice were then treated with vehicle or vildagliptin (intraperitoneally, 10 mg/kg, once daily for 14 consecutive days from 1 day before the first administration of LPS.). Flow cytometry, immunohistochemical staining, and quantitative polymerase chain reaction (qPCR) analysis was used to assess cell dynamics and EndMT function in lung samples from the mice. Lung tissue samples from treated mice revealed obvious inflammatory reactions and typical interstitial fibrosis 2 days and 28 days after LPS challenge. Quantitative flow cytometric analysis showed that the number of pulmonary vascular endothelial cells (PVECs) expressing alpha-smooth muscle actin (α-SMA) or S100 calcium-binding protein A4 (S100A4) increased 28 days after LPS challenge. Similar increases in expression were also confirmed by qPCR of mRNA from isolated PVECs. EndMT cells had higher proliferative activity and migration activity than mesenchymal cells. All of these changes were alleviated by intraperitoneal injection of vildagliptin. Interestingly, vildagliptin and linagliptin significantly attenuated EndMT in the absence of immune

Role of endogenous nitric oxide on PAF-induced vascular and respiratory effects

Directory of Open Access Journals (Sweden)

M. Clement

1995-01-01

Full Text Available The role of endogenous nitric oxide (NO on vascular and respiratory smooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF-induced shock and airway hyperresponsiveness was also studied. PAF (50 ng/kg, i.v. was administered before and after pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., an NO synthesis inhibitor. PAF was also administered to three of these pigs after indomethacin infusion (3 mg/kg, i.v.. In normal pigs, L-NAME increased systemic and pulmonary vascular resistances, caused pulmonary hypertension and reduced cardiac output and stroke volume. The pulmonary vascular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO synthesis enhanced the PAF-dependent increase in total, intrinsic and viscoelastic lung resistances, without affecting lung elastances or cardiac activity. The systemic hypotensive effect of PAF was not abolished by pretreatment with L-NAME or indomethacin. This indicates that systemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependent respiratory effects.

Pregnancy in women with pulmonary hypertension

NARCIS (Netherlands)

Pieper, P. G.; Hoendermis, E. S.

2011-01-01

Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced

[Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

Science.gov (United States)

Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

2015-01-01

Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Lung Perfusion SPECT: Application in a Patient With Tetralogy of Fallot and Suspected Pulmonary Thromboemboli

International Nuclear Information System (INIS)

Ranji Amjad, Mina; Abbasi, Mehrshad; Farzanehfar, Saeed

2015-01-01

A 22-year-old woman presented with acute left-sided pleuritic chest pain and dyspnea 6 days after surgery for revision of the stenotic central aortopulmonary shunt. She had a history of tetralogy of Fallot (TOF), pulmonary valve stenosis, ventricular septal defect and major aortopulmonary collateral artery. Her Waterston shunt was placed when she was 5 years old and stented and re-dilated after stenosis. Acute pulmonary thromboemboli (PTE) was suspected and pulmonary perfusion scan was performed with 4 mCi 99m Technetium labeled macroaggregated albumin. The left lung was globally hypoperfused with evident uptake in the brain, renal parenchyma and thyroid. SPECT images revealed a segmental wedge-shaped peripheral defect in the posterior segment of the left upper lobe. The scan was interpreted as acute/chronic PTE or vascular abnormality. CT angiography excluded PTE; nevertheless the patient was treated with a therapeutic dose of heparin changed to warfarin and was discharged with improvement of the symptoms. Pulmonary artery angiography was not performed

S-Nitrosylation and the Development of Pulmonary Hypertension

National Research Council Canada - National Science Library

Palmer, Lisa A

2008-01-01

.... In the current studies, N-acetyl cysteine (NAC) was used as a bait reactant to measure NO transfer reactions in the blood and the vascular effects of these reactions in the pulmonary vasculature...

Pulmonary hypertension in chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Aguirre F, Carlos E; Torres D, Carlos A.

2010-01-01

Pulmonary hypertension (PH) is a relatively common complication of chronic obstructive pulmonary disease (COPD). Its appearance during the course of COPD is associated with a worsened prognosis, due to reduced life expectancy and greater use of health care resources. Although a well-defined lineal relationship has not been shown, the prevalence of PH in patients with COPD is higher in cases characterized by greater obstruction and severity. PH is infrequent in cases of mild and moderate COPD. In cases of COPD, PH is generally mild or moderate, and seldom impairs right ventricular function. In many cases it is not apparent during rest, and manifests itself during exercise. PH can be severe or out of proportion with the severity of COPD. In this situation, the possibility of associated conditions should be explored, although COPD might be the only final explanation. There is scarce knowledge about the prevalence and behavior of PH in patients with COPD residing at intermediate and high altitudes (>2.500 meters above sea level), which is a common situation in Latin America and Asia. PH in COPD is not exclusively related with hypoxia/hypoxaemia and hypercapnia. The mechanical disturbances related with COPD (hyper inflation and high alveolar pressure) and inflammation may prevail as causes of endothelial injury and remodeling of pulmonary circulation, which contribute to increased pulmonary vascular pressure and resistance. The appearance of signs of cor p ulmonale indicates advanced PH. This condition should therefore be suspected early when dyspnoea, hypoxaemia, and impairment of diffusion are not in keeping with the degree of obstruction. PH is confirmed by Doppler echocardiography. Right heart catheterization may be justified in selected cases. Long-term oxygen therapy is the only intervention proven to be temporarily useful. Conventional vasodilators do not produce medium- or long-term improvement and can be detrimental to the ventilation-perfusion relation

Platelet-rich plasma extract prevents pulmonary edema through angiopoietin-Tie2 signaling.

Science.gov (United States)

Mammoto, Tadanori; Jiang, Amanda; Jiang, Elisabeth; Mammoto, Akiko

2015-01-01

Increased vascular permeability contributes to life-threatening pathological conditions, such as acute respiratory distress syndrome. Current treatments for sepsis-induced pulmonary edema rely on low-tidal volume mechanical ventilation, fluid management, and pharmacological use of a single angiogenic or chemical factor with antipermeability activity. However, it is becoming clear that a combination of multiple angiogenic/chemical factors rather than a single factor is required for maintaining stable and functional blood vessels. We have demonstrated that mouse platelet-rich plasma (PRP) extract contains abundant angiopoietin (Ang) 1 and multiple other factors (e.g., platelet-derived growth factor), which potentially stabilize vascular integrity. Here, we show that PRP extract increases tyrosine phosphorylation levels of Tunica internal endothelial cell kinase (Tie2) and attenuates disruption of cell-cell junctional integrity induced by inflammatory cytokine in cultured human microvascular endothelial cells. Systemic injection of PRP extract also increases Tie2 phosphorylation in mouse lung and prevents endotoxin-induced pulmonary edema and the consequent decreases in lung compliance and exercise intolerance resulting from endotoxin challenge. Soluble Tie2 receptor, which inhibits Ang-Tie2 signaling, suppresses the ability of PRP extract to inhibit pulmonary edema in mouse lung. These results suggest that PRP extract prevents endotoxin-induced pulmonary edema mainly through Ang-Tie2 signaling, and PRP extract could be a potential therapeutic strategy for sepsis-induced pulmonary edema and various lung diseases caused by abnormal vascular permeability.

[Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension].

Science.gov (United States)

Navarro, Carmen

2006-11-01

Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension Lung disease is present in most of the patients with systemic sclerosis and is now the most important cause of mortality. Interstitial lung disease and pulmonary hypertension are, so far, the main disorders found and both are difficult to detect at the earliest stages. However, diagnostic tools such as immunological test, lung function test, high resolution CT, bronchoalveolar lavage, echocardiography, right-side cardiac catheterization, or lung biopsy are necessary to accurately evaluate the clinical status and allow to improve the management organ-specific ad hoc. Progress in immunological and vascular therapies as well as other emergence drugs offer new expectations to scleroderma patients. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

Pulmonary venous thrombosis secondary to radiofrequency ablation of the pulmonary veins.

Science.gov (United States)

López-Reyes, Raquel; García-Ortega, Alberto; Torrents, Ana; Feced, Laura; Calvillo, Pilar; Libreros-Niño, Eugenia Alejandra; Escrivá-Peiró, Juan; Nauffal, Dolores

2018-01-01

Pulmonary Vein Thrombosis (PVT) is a rare and underdiagnosed entity produced by local mechanical nature mechanisms, vascular torsion or direct injury to the vein. PVT has been described in clinical cases or small multicenter series mainly in relation to pulmonary vein stenosis, metastatic carcinoma, fibrosing mediastinitis, as an early surgical complication of lung transplantation lobectomy and radiofrequency ablation performed in patients with atrial fibrillation, although in some cases the cause is not known. We report the case of a 57 years old male with history of atrial fibrillation treated by radiofrequency ablation who was admitted in our center because of a two-week history of consistent pleuritic pain in the left hemithorax and low-grade hemoptysis and a lung consolidation treated as a pneumonia with antibiotic but not responding to medical therapy. In view of the poor evolution of the patient, computed tomography angiography was performed with findings of PVT and secondary venous infarction and anticoagulation therapy was optimized. At the end, pulmonary resection was performed due to hemorrhagic recurrence. PVT remains a rare complication of radiofrequency ablation and other procedures involving pulmonary veins. Clinical suspicion and early diagnosis is crucial because is a potentially life-threatening entity.

Hyperthyroidism and pulmonary hypertension: an important association.

Science.gov (United States)

Vallabhajosula, Sailaja; Radhi, Saba; Cevik, Cihan; Alalawi, Raed; Raj, Rishi; Nugent, Kenneth

2011-12-01

Pulmonary hypertension is a complex disorder with multiple etiologies. The World Health Organization Group 5 (unclear multifactorial mechanisms) includes patients with thyroid disorders. The authors reviewed the literature on the association between hyperthyroidism and pulmonary hypertension and identified 20 publications reporting 164 patients with treatment outcomes. The systolic pulmonary artery (PA) pressures in these patients ranged from 28 to 78 mm Hg. They were treated with antithyroid medications, radioactive iodine and surgery. The mean pretherapy PA systolic pressure was 39 mm Hg; the mean posttreatment pressure was 30 mm Hg. Pulmonary hypertension should be considered in hyperthyroid patients with dyspnea. All patients with pulmonary hypertension should be screened for hyperthyroidism, because the treatment of hyperthyroidism can reduce PA pressures, potentially avoid the side-effects and costs with current therapies for pulmonary hypertension and limit the consequences of untreated hyperthyroidism. However, the long-term outcome in these patients is uncertain, and this issue needs more study. Changes in the pulmonary circulation and molecular regulators of vascular remodeling likely explain this association.

Effects of bone marrow-derived cells on monocrotaline- and hypoxia-induced pulmonary hypertension in mice

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Vainchenker William

2007-01-01

Full Text Available Abstract Background Bone marrow -derived cells (BMDCs can either limit or contribute to the process of pulmonary vascular remodeling. Whether the difference in their effects depends on the mechanism of pulmonary hypertension (PH remains unknown. Objectives We investigated the effect of BMDCs on PH induced in mice by either monocrotaline or exposure to chronic hypoxia. Methods Intravenous administration of the active monocrotaline metabolite (monocrotaline pyrrole, MCTp to C57BL/6 mice induced PH within 15 days, due to remodeling of small distal vessels. Three days after the MCTp injection, the mice were injected with BMDCs harvested from femurs and tibias of donor mice treated with 5-fluorouracil (3.5 mg IP/animal to deplete mature cells and to allow proliferation of progenitor cells. Results BMDCs significantly attenuated PH as assessed by reductions in right ventricular systolic pressure (20 ± 1 mmHg vs. 27 ± 1 mmHg, P ≤ 0.01, right ventricle weight/left ventricle+septum weight ratio (0.29 ± 0.02 vs. 0.36 ± 0.01, P ≤ 0.03, and percentage of muscularized vessels (26.4% vs. 33.5%, P ≤ 0.05, compared to control animals treated with irradiated BMDCs. Tracking cells from constitutive GFP-expressing male donor mice with anti-GFP antibodies or chromosome Y level measurement by quantitative real-time PCR showed BMDCs in the lung. In contrast, chronically hypoxic mice subjected to the same procedure failed to show improvement in PH. Conclusion These results show that BMDCs limit pulmonary vascular remodeling induced by vascular injury but not by hypoxia.

Tyrosine phosphorylation of Kv1.5 is upregulated in intrauterine growth retardation rats with exaggerated pulmonary hypertension

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L.C. Fu

2017-09-01

Full Text Available Intrauterine growth retardation (IUGR is associated with the development of adult-onset diseases, including pulmonary hypertension. However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular dysfunction later in life is not fully understood. Here, we investigated the role of tyrosine phosphorylation of voltage-gated potassium channel 1.5 (Kv1.5 in this prenatal event that results in exaggerated adult vascular dysfunction. A rat model of chronic hypoxia (2 weeks of hypoxia at 12 weeks old following IUGR was used to investigate the physiological and structural effect of intrauterine malnutrition on the pulmonary artery by evaluating pulmonary artery systolic pressure and vascular diameter in male rats. Kv1.5 expression and tyrosine phosphorylation in pulmonary artery smooth muscle cells (PASMCs were determined. We found that IUGR increased mean pulmonary artery pressure and resulted in thicker pulmonary artery smooth muscle layer in 14-week-old rats after 2 weeks of hypoxia, while no difference was observed in normoxia groups. In the PASMCs of IUGR-hypoxia rats, Kv1.5 mRNA and protein expression decreased while that of tyrosine-phosphorylated Kv1.5 significantly increased. These results demonstrate that IUGR leads to exaggerated chronic hypoxia pulmonary arterial hypertension (CH-PAH in association with decreased Kv1.5 expression in PASMCs. This phenomenon may be mediated by increased tyrosine phosphorylation of Kv1.5 in PASMCs and it provides new insight into the prevention and treatment of IUGR-related CH-PAH.

Improved pulmonary function in working divers breathing nitrox at shallow depths

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Fitzpatrick, Daniel T.; Conkin, Johnny

2003-01-01

INTRODUCTION: There is limited data about the long-term pulmonary effects of nitrox use in divers at shallow depths. This study examined changes in pulmonary function in a cohort of working divers breathing a 46% oxygen enriched mixture while diving at depths less than 12 m. METHODS: A total of 43 working divers from the Neutral Buoyancy Laboratory (NBL), NASA-Johnson Space Center completed a questionnaire providing information on diving history prior to NBL employment, diving history outside the NBL since employment, and smoking history. Cumulative dive hours were obtained from the NBL dive-time database. Medical records were reviewed to obtain the diver's height, weight, and pulmonary function measurements from initial pre-dive, first year and third year annual medical examinations. RESULTS: The initial forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were greater than predicted, 104% and 102%, respectively. After 3 yr of diving at the NBL, both the FVC and FEV1 showed a significant (p volumes. Regular diving with nitrox at shallow depths over a 3-yr period did not impair pulmonary function. Improvements in FVC and FEV1 were primarily due to a training effect.

Pulmonary uptake of thallium-201 in patients with congenital heart disease; Comparison between total anomalous pulmonary venous connection and tetralogy of Fallot

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Kohata, Tohru; Ono, Yasuo; Iwatani, Hajime; Fukushima, Hideki; Kamiya, Tetsuro; Yagihara, Toshikatsu; Nishimura, Tsunehiko; Takamiya, Makoto (National Cardiovascular Center, Suita, Osaka (Japan))

1992-01-01

To evaluate the pulmonary extravascular space in patients with congenital heart disease, lung uptake of Tl-201 was quantitatively studied. Patients' diseases consisted of total anomalous pulmonary venous connection (TAPVC)--supracardiac (I), paracardiac (II) and infracardiac (III) types--, tetralogy of Fallot (T/F), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). Tl-201 imaging was performed before operation and in the early and late stages after operation. Twenty-five other patients with arrhythemias or a history of Kawasaki disease without perfusion defects served as controls. Lung uptake of Tl-201 was analyzed with a computer using the anterior image of the chest, and the averge count ratio of the right lung (P) to the left ventricular wall (LV) was calculated. P/LV values were compared between the patients before and after operation, and differences in anatomical types in TAPVC were also evaluated. In TAPVC, P/LV values decreased gradually after operation, but were significantly higher than those of controls even in the late stage. In the late stage after operation, type I TAPVC had significantly higher P/LV values than those of type-II. In T/F, the P/LV values were significantly higher after operation, even in the late stage, than before operation. In the VSD or PDA group, the P/LV value returned to normal after operation and was significantly lower than that before operation. In conclusion, TAPVC patients was considered to have a larger pulmonary extravascular space even in the late stage after operation, suggesting a sign of pulmonary congestion due to intrapulmonary vascular damage in utero. In T/F, scanty pulmonary vascular beds before operation were perfused with increased pulmonary blood flow after operation. Therefore, postoperative increases in pulmonary blood flow may be responsible for the increased pulmonary extravascular space. (N.K.).

Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

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Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

2015-01-01

Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

Pulmonary hypertension associated with non-cirrhotic portal hypertension in systemic lupus erythematosus.

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Woolf, D.; Voigt, M. D.; Jaskiewicz, K.; Kalla, A. A.

1994-01-01

A case of non-cirrhotic portal hypertension in a patient with systemic lupus erythematosus, the first of our knowledge, is described. Severe pulmonary hypertension was associated with the portal hypertension and with markers of active auto-immunity. Pulmonary hypertension has not previously been associated with non-cirrhotic portal hypertension. The coexistence of vasculopathy of the portal and pulmonary vascular beds in this patient with active autoimmunity supports the postulate that portal...

Pulmonary edema: radiographic differential diagnosis

International Nuclear Information System (INIS)

Yoo, Dong Soo; Choi, Young Hi; Kim, Seung Cheol; An, Ji Hyun; Lee, Jee Young; Park, Hee Hong

1997-01-01

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

The Right Ventricle Explains Sex Differences in Survival in Idiopathic Pulmonary Arterial Hypertension

NARCIS (Netherlands)

Jacobs, W.; van de Veerdonk, M.C.; Trip, P.; de Man, F.S.; Heymans, M.W.; Marcus, J.T.; Kawut, S.M.; Bogaard, H.J.; Boonstra, A.; Vonk-Noordegraaf, A.

2014-01-01

Background: Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate

Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

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McLoughlin Paul

2011-01-01

Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

Diffuse pulmonary ossification. A case report

International Nuclear Information System (INIS)

Torres D, Carlos A; Ojeda L, Paulina

1997-01-01

The diffuse pulmonary ossification (DPO) is a rare disease characterized by metaplastic formation of bony tissue in the lung parenchyma. Generally it is associated with other disorders as mitral stenosis and interstitial fibrosis. Sometimes the DPO is idiopathic. We report the case of a 49-year-old man who presented with cough and hemoptysis. The radiological findings suggested an interstitial lung disease. The fiber optic bronchoscopy was normal. The pulmonary function tests showed a mild airway obstruction. The bacteriological and serological studies for tuberculosis, mycosis, and collagen-vascular disease were negatives. An open lung biopsy was performed and the pathologic findings were interpreted as diffuse pulmonary ossification (DPO). Any other disease was found; so, in this case the DPO was classified as idiopathic

Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells

DEFF Research Database (Denmark)

Cao, Yi; Jacobsen, Nicklas Raun; Danielsen, Pernille Høgh

2014-01-01

Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice,...

Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

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Xu Xue-Feng

2013-02-01

Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

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

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

2018-06-01

Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular 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, sex, 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 = .012), along with reduced log(pulmonary artery capacitance) (P = .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 Elsevier Inc. All rights reserved.

Gap junction protein connexin43 exacerbates lung vascular permeability.

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James J O'Donnell

Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

Impact of Balloon Pulmonary Angioplasty on Hemodynamics and Clinical Outcomes in Patients with Chronic Thromboembolic Pulmonary Hypertension: the Initial Korean Experience.

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Kwon, Woochan; Yang, Jeong Hoon; Park, Taek Kyu; Chang, Sung A; Jung, Dong Seop; Cho, Young Seok; Kim, Sung Mok; Kim, Tae Jung; Park, Hye Yoon; Choi, Seung Hyuk; Kim, Duk Kyung

2018-01-22

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, not all patients are eligible for PEA, and some patients experience recurrence of pulmonary hypertension even after PEA. Patients who underwent balloon pulmonary angioplasty (BPA) between December 2015 and April 2017 were enrolled from the Samsung Medical Center CTEPH registry. Enrolled patients underwent right heart catheterization, echocardiography, and 6-minute walk distance (6MWD) at baseline, 4 and 24 weeks after their first BPA session. We compared clinical and hemodynamic parameters at the baseline and last BPA session. Fifty-two BPA sessions were performed in 15 patients, six of whom had a history of PEA. BPA resulted in improvements in World Health Organization (WHO) functional class (2.9 ± 0.8 to 1.7 ± 0.6, P = 0.002), 6MWD (387.0 ± 86.4 to 453.4 ± 64.8 m, P = 0.01), tricuspid annular plane systolic excursion (14.1 ± 3.6 to 15.6 ± 4.3 mm, P = 0.03) and hemodynamics, including a decline in mean pulmonary artery pressure (41.1 ± 13.1 to 32.1 ± 9.5 mmHg, P < 0.001) and in pulmonary vascular resistance (607.4 ± 452.3 to 406.7 ± 265.4 dyne.sec.cm⁻⁵, P = 0.01) but not in cardiac index (2.94 ± 0.79 to 2.96 ± 0.93 L/min/m², P = 0.92). Six cases of complications were recorded, including two cases of reperfusion injury. BPA might be a safe and effective treatment strategy for both inoperable CTEPH patients and patients with residual pulmonary hypertension after PEA. © 2018 The Korean Academy of Medical Sciences.

Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

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Levitzky, Michael G

2006-03-01

"Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

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Upadhyaya, Jasbir D; Singh, Nisha; Sikarwar, Anurag S; Chakraborty, Raja; Pydi, Sai P; Bhullar, Rajinder P; Dakshinamurti, Shyamala; Chelikani, Prashen

2014-01-01

Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

Non-vascular interventional therapy for respiratory diseases

International Nuclear Information System (INIS)

Ji Hongjian; Chen Liping; Wang Hui; Cheng Yongde

2009-01-01

To review the recent literature relating to non-vascular interventional therapy of respiratory diseases. Metal airway stent insertion can immediately relieve tracheobronchial obstruction and improve pulmonary function. However, as there is a high occurrence of the restenosis after stent insertion, it should be very careful to use metal stenting to treat the benign airway obstruction. Compared with traditional lung volume reduction surgery in treating severe emphysema, bronchoscopic lung volume reduction appears to be effective, safe and less invasive, although its clinical usefullness need to be further proved. Endoscopic occlusion of bronchial fistula represents an effective alternative to surgical treatment. Percutaneous lung biopsy under ultrasound or CT guidance has been applied successfully in the management of both benign and malignant lesions. (authors)

Use of computed tomography and automated software for quantitative analysis of the vasculature of patients with pulmonary hypertension

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Wada, Danilo Tadao; Pádua, Adriana Ignácio de; Lima Filho, Moyses Oliveira; Marin Neto, José Antonio; Elias Júnior, Jorge; Baddini-Martinez, José; Santos, Marcel Koenigkam, E-mail: danilowada@yahoo.com.br [Universidade de São Paulo (HCFMRP/USP), Ribeirão Preto, SP (Brazil). Faculdade de Medicina. Hospital das Clínicas

2017-11-15

Objective: To perform a quantitative analysis of the lung parenchyma and pulmonary vasculature of patients with pulmonary hypertension (PH) on computed tomography angiography (CTA) images, using automated software. Materials And Methods: We retrospectively analyzed the CTA findings and clinical records of 45 patients with PH (17 males and 28 females), in comparison with a control group of 20 healthy individuals (7 males and 13 females); the mean age differed significantly between the two groups (53 ± 14.7 vs. 35 ± 9.6 years; p = 0.0001). Results: The automated analysis showed that, in comparison with the controls, the patients with PH showed lower 10{sup th} percentile values for lung density, higher vascular volumes in the right upper lung lobe, and higher vascular volume ratios between the upper and lower lobes. In our quantitative analysis, we found no differences among the various PH subgroups. We inferred that a difference in the 10{sup th} percentile values indicates areas of hypovolaemia in patients with PH and that a difference in pulmonary vascular volumes indicates redistribution of the pulmonary vasculature and an increase in pulmonary vasculature resistance. Conclusion: Automated analysis of pulmonary vessels on CTA images revealed alterations and could represent an objective diagnostic tool for the evaluation of patients with PH. (author)

Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction

NARCIS (Netherlands)

B. Houweling (Birgit); D. Merkus (Daphne); O. Sorop (Oana); F. Boomsma (Frans); D.J.G.M. Duncker (Dirk)

2006-01-01

textabstractWe previously observed that pulmonary hypertension secondary to myocardial infarction (MI) in swine is characterized by elevated plasma endothelin (ET) levels and pulmonary vascular resistance (PVR). Consequently, we tested the hypothesis that an increased ET-mediated vasoconstrictor

Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

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Dong-Mei Jiang

Full Text Available BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH. Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2 expression, prostacyclin (PGI2 and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

[Early diagnosis and therapy in pulmonary hypertension--aspects of a vision].

Science.gov (United States)

Ewert, R; Olschewski, H; Ghofrani, H A; Opitz, C F

2013-07-01

In patients with pulmonary hypertension progressive vascular changes in the lung precede the clinical and hemodynamic manifestations of the disease. Therefore, early diagnosis and timely treatment of the disease are crucial. This has been the topic of an expert meeting in Greifswald, Germany in June 2012. The current definition of pulmonary hypertension requires a mean pulmonary artery pressure ≥ 25 mmHg at rest, a hemodynamic abnormality already reflecting pulmonary vascular changes beyond early disease. There is increasing evidence supporting the concept that a lower pressure threshold at rest or an abnormal pressure response with exercise better characterize early disease. While right heart catheterization at rest remains the diagnostic gold standard other methods for detecting early disease are explored with echocardiography being the most frequently used technique. Targeted therapy has been approved for patients with pulmonary arterial hypertension (PAH, WHO-group I) in functional class II-IV. Preliminary data in functional class I patients suggest therapeutic potential of theses drugs in early disease as well. Current guidelines propose therapeutic goals based on parameters with prognostic importance. However, these recommendations are based on mostly retrospective analyses of pre-treatment data obtained in patients with pulmonary hypertension in functional class II-IV. Therefore, evidence-based therapeutic goals for early interventions in functional class I patients are lacking. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical application of gadolinium-enhanced three-dimensional pulmonary MR angiography

International Nuclear Information System (INIS)

Takano, Katsuyuki

1999-01-01

Twenty-nine patients with suspected pulmonary lesions, and three normal volunteers, underwent gadolinium-enhanced three-dimensional (3D) pulmonary MR angiography (MRA). The MRA were obtained during intravenous administration of gadolinium-based contrast material, in a single breath-hold. Conspicuity of the normal pulmonary segmental arteries was estimated on the MRA. Abnormal findings such as ''vascular involvement'', ''abnormal connection'', stenosis'', or ''dilatation'' on the MRA were compared with those on conventional angiography or CT. Normal pulmonary segmental arteries, except for A 4,5,6,8and9 of the left pulmonary artery, could be clearly visualized. Blind reading of four different findings lead to characteristic findings for each pulmonary disease that can be aid in their differential diagnoses. This technique shows promise as a noninvasive diagnosis of lung diseases. (author)

Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure, bidirectional bronchiolo-pulmonar shunting and water evaporation.

Science.gov (United States)

Kurbel, Sven; Kurbel, Beatrica; Gulam, Danijela; Spajić, Borislav

2010-06-01

The main puzzle of the pulmonary circulation is how the alveolar spaces remain dry over a wide range of pulmonary vascular pressures and blood flows. Although normal hydrostatic pressure in pulmonary capillaries is probably always below 10 mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that some fluid filtration through capillary walls does occur, while the increased lymph drainage prevents alveolar fluid accumulation. The lack of a measurable pressure drop along pulmonary capillaries makes the classic description of Starling forces unsuitable to the low pressure, low resistance pulmonary circulation. Here presented model of pulmonary fluid traffic describes lungs as a matrix of small vascular units, each consisting of alveoli whose capillaries are anastomotically linked to the bronchiolar capillaries perfused by a single bronchiolar arteriole. It proposes that filtration and absorption in pulmonary and in bronchiolar capillaries happen as alternating periods of low and of increased perfusion pressures. The model is based on three levels of filtration control: short filtration phases due to respiratory cycle of the whole lung are modulated by bidirectional bronchiolo-pulmonar shunting independently in each small vascular unit, while fluid evaporation from alveolar groups further tunes local filtration. These mechanisms are used to describe a self-sustaining regulator that allows optimal fluid traffic in different settings. The proposed concept is used to describe development of pulmonary edema in several clinical entities (exercise in wet or dry climate, left heart failure, people who rapidly move to high altitudes, acute cyanide and carbon monoxide poisoning, large pulmonary embolisms). .

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

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Rui-Xing Wang

2015-03-01

Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

Imaging in congenital pulmonary vein anomalies: the role of computed tomography

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Dyer, Kevin Todd; McQuiston, Andrew Douglas [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Hlavacek, Anthony Marcus; Pietris, Nicholas Peter [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology Department of Pediatrics, Charleston, SC (United States); Meinel, Felix Gabriel [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Ludwig-Maximilians-University Hospital, Institute for Clinical Radiology, Munich (Germany); De Cecco, Carlo Nicola [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); University of Rome ' ' Sapienza' ' - Polo Pontino, Department of Radiological Sciences Oncology and Pathology, Latina (Italy); Schoepf, Uwe Joseph [Medical University of South Carolina, Division of Cardiology Department of Medicine, Charleston, SC (United States); Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology Department of Pediatrics, Charleston, SC (United States)

2014-09-15

Pulmonary venous anomalies comprise a wide spectrum of anatomical variations and their clinical presentations may vary from the relatively benign single partial anomalous pulmonary venous connection (PAPVC) to the critical obstructed total anomalous pulmonary venous connection (TAPVC). We briefly review the common anomalies encountered, while highlighting the utility that computed tomographic angiography (CTA) provides for this spectrum of extracardiac vascular malformations and connections. CTA has established itself as an invaluable imaging modality in these patients. A detailed knowledge of the CTA imaging findings in pulmonary venous anomalies is crucial to guide clinical decision-making in these patients. (orig.)

Late Posthemorrhagic Structural and Functional Changes in Pulmonary Circulation Arteries

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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

HRCT of the lung in collagen vascular diseases

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Diederich, S.; Roos, N.; Schmitz-Linneweber, B.; Gaubitz, M.; Peters, P.E.

1996-01-01

Collagen vascular diseases, representing systemic soft tissue disorders, may cause a broad spectrum of pathologic changes of the respiratory tract. The type and extent of manifestations can vary considerably among individuals and entities. This survey describes the chest radiographic and, in particular, high-resolution computed tomographic and, in particular, high-resolution computed tomographic (HRCT) findings of individual lesions of the respiratory tract. It includes fibrosing alveolitis (alveolitis, interstitial pneumonia, pulmonary fibrosis) and bronchial (bronchitis/bronchiolitis, bronchiectasis), pleural and vascular manifestations, as well as lymphadenopathy and abnormalities related to therapy. We present typical patterns of changes in progressive systemic sclerosis (PSS, scleroderma), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD, Sharp syndrome), Sjoegren syndrome, overlap syndrome and rheumatoid arthritis (RA). Furthermore, we describe findings which are specific for individual entities such as esophageal involvement in PSS, acute pneumonitis and pulmonary hemorrhage in SLE, lymphoproliferative disease in Sjoegren syndrome and necrobiotic nodules in RA. (orig.) [de

Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

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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

Five-year results from a prospective multicentre study of percutaneous pulmonary valve implantation demonstrate sustained removal of significant pulmonary regurgitation, improved right ventricular outflow tract obstruction and improved quality of life

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Hager, Alfred; Schubert, Stephan; Ewert, Peter

2017-01-01

. The EQ-5D quality of life utility index and visual analogue scale scores were both significantly improved six months post PPVI and remained so at five years. CONCLUSIONS: Five-year results following PPVI demonstrate resolved moderate or severe pulmonary regurgitation, improved right ventricular outflow...

Pulmonary artery pressure increases during commercial air travel in healthy passengers.

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Smith, Thomas G; Talbot, Nick P; Chang, Rae W; Wilkinson, Elizabeth; Nickol, Annabel H; Newman, David G; Robbins, Peter A; Dorrington, Keith L

2012-07-01

It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients.

Improved pulmonary nodule classification utilizing quantitative lung parenchyma features.

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Dilger, Samantha K N; Uthoff, Johanna; Judisch, Alexandra; Hammond, Emily; Mott, Sarah L; Smith, Brian J; Newell, John D; Hoffman, Eric A; Sieren, Jessica C

2015-10-01

Current computer-aided diagnosis (CAD) models for determining pulmonary nodule malignancy characterize nodule shape, density, and border in computed tomography (CT) data. Analyzing the lung parenchyma surrounding the nodule has been minimally explored. We hypothesize that improved nodule classification is achievable by including features quantified from the surrounding lung tissue. To explore this hypothesis, we have developed expanded quantitative CT feature extraction techniques, including volumetric Laws texture energy measures for the parenchyma and nodule, border descriptors using ray-casting and rubber-band straightening, histogram features characterizing densities, and global lung measurements. Using stepwise forward selection and leave-one-case-out cross-validation, a neural network was used for classification. When applied to 50 nodules (22 malignant and 28 benign) from high-resolution CT scans, 52 features (8 nodule, 39 parenchymal, and 5 global) were statistically significant. Nodule-only features yielded an area under the ROC curve of 0.918 (including nodule size) and 0.872 (excluding nodule size). Performance was improved through inclusion of parenchymal (0.938) and global features (0.932). These results show a trend toward increased performance when the parenchyma is included, coupled with the large number of significant parenchymal features that support our hypothesis: the pulmonary parenchyma is influenced differentially by malignant versus benign nodules, assisting CAD-based nodule characterizations.

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

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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.

Pulmonary arterial hypertension associated with congenital heart disease

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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.

Echocardiographic and Hemodynamic Predictors of Survival in Precapillary Pulmonary Hypertension: Seven-Year Follow-Up.

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Grapsa, Julia; Pereira Nunes, Maria Carmo; Tan, Timothy C; Cabrita, Ines Zimbarra; Coulter, Taryn; Smith, Benjamin C F; Dawson, David; Gibbs, J Simon R; Nihoyannopoulos, Petros

2015-06-01

In this study, we looked at the prognostic value of echocardiographic and hemodynamic measures in a large cohort of patients with precapillary pulmonary hypertension before and after initiation of treatment. Data were collected prospectively in a cohort of consecutive patients with precapillary pulmonary hypertension referred between 2002 and 2011. A range of clinical and echocardiographic variables were collected and stored on a database to assess predictors of survival. Invasive hemodynamic data including pulmonary artery pressure, pulmonary vascular resistance, capillary wedge pressure, and cardiac index were also obtained at baseline in all patients. Outcome was defined as mortality because of cardiovascular-related death. The study cohort comprised 777 patients (514 women) with precapillary pulmonary hypertension. A total of 195 (25%) died. In multivariable analysis, moderate or severe tricuspid regurgitation (hazard ratio [HR], 26.537; 95% confidence interval, 11.536-61.044; P<0.001), right ventricular myocardial performance index (HR, 3.421; 95% confidence interval, 1.777-6.584; P<0.001), and the presence of pericardial effusion (HR, 1.38; 95% confidence interval, 1.023-1.862; P=0.035) were independent predictors of mortality. High pulmonary vascular resistance and right atrial pressure by invasive hemodynamic measurements were independent predictors of mortality (HR, 1.084; 95% confidence interval, 1.041-1.130, and 1.079, respectively; 95% confidence interval, 1.049-1.111; P<0.001 for both), whereas patients with a higher cardiac index had better survival overall (HR, 0.384; 95% confidence interval, 0.307-0.481; P<0.001). Right ventricular dysfunction, moderate-severe tricuspid regurgitation, low cardiac index, and raised right atrial pressure were associated with poor survival for both pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertensive disease patients. The severity of tricuspid regurgitation, myocardial performance index

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

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

2014-01-01

Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/A<0.92(n=59) to determine serum vascular biomarkers that were predictive of this vasculopathy. Outcome measures The primary outcome of this study was to identify a PA/A ratio in a cohort of individuals exposed to WTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of

Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.

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Pfister, Sandra L

2011-04-01

Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.

Quality of provided care in vascular surgery : outcome assessment & improvement strategies

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Flu, Hans Christiaan

2010-01-01

The aim of this thesis was to evaluate the quality of care in vascular surgery in end-stage renal disease (ESRD) and peripheral arterial occlusive disease (PAOD): intermittent claudication (IC) and critical lower limb ischaemia (CLI) patients. Therefore firstly it focused on the improvement of the

Information content of pulmonary perfusion scintigraphy

International Nuclear Information System (INIS)

Kunieda, Takeyoshi

1982-01-01

A scinticamera computer system was used to measure the distribution of blood flow in both upright and supine lungs sequentially with the same counting geometry. The counting ratio of the upper half to the lower half lung, and the difference of distribution indices between supine lung and upright lung which is the fraction of postural change from the supine upper half to upright lower half lung to total distribution of blood flow, were referred to as ''U/L ratio'' and postural ''Change of Distribution'' respectively. U/L ratio correlated well with left atrial mean pressure (r = 0.87, p < 0.001) with the regression equation and Change of Distribution correlated well with pulmonary artery mean pressure (PAm) (r = -0.88, p < 0.001) in cardiac diseases. The relationship between the Change of Distribution and PAm was investigated using various regression analyses and the best fit was obtained by logarithmic regression (r = -0.92) with the regression equation. This regression equation means that there is no change of distribution of pulmonary blood flow with pulmonary artery pressure over 58 mmHg and that entire pulmonary blood flow comes to the lower half lung when the pulmonary artery pressure decreases to zero level. Pulmonary parenchymal and vascular disorders including primary pulmonary hypertension also held the same relationship with PAm. The relationship between upright U/L ratio and postural Change of Distribution permitted differentiation between precapillary pulmonary hypertension and postcapillary pulmonary hypertension. (J.P.N.)

Central extracorporeal membrane oxygenation requiring pulmonary arterial venting after near-drowning.

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Kimura, Mitsutoshi; Kinoshita, Osamu; Fujimoto, Yoshifumi; Murakami, Arata; Shindo, Takahiro; Kashiwa, Koichi; Ono, Minoru

2014-02-01

Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning.

High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.

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Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J; Presson, Robert G; Petrache, Irina; Kline, Jeffrey; Lahm, Tim

2017-02-01

Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.

Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics

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Leína Zorzanelli

2016-01-01

Full Text Available Background and Objective. Inflammation is central in the pathogenesis of pulmonary hypertension. We investigated how serum cytokines correlate with clinical features, hemodynamics, and lung histology in young patients with pulmonary hypertension associated with congenital cardiac shunts. Design. Prospective, observational study. Methods and Results. Patients (n=44 were aged 2.6 to 37.6 months. Group I patients (n=31 were characterized by pulmonary congestion and higher pulmonary blood flow compared to group II (p=0.022, with no need for preoperative cardiac catheterization. Group II patients (n=13 had no congestive features. At catheterization, they had elevated pulmonary vascular resistance (5.7 [4.4–7.4] Wood units·m2, geometric mean with 95% CI. Cytokines were measured by chemiluminescence. Macrophage migration inhibitory factor (MIF was found to be inversely related to pulmonary blood flow (r=-0.33, p=0.026 and was higher in group II (high pulmonary vascular resistance compared to group I (high pulmonary blood flow (p=0.017. In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted was characteristically elevated in Group I (p=0.022. Interleukin 16 was also negatively related to pulmonary blood flow (rS=-0.33, p=0.029 and was higher in patients with obstructive vasculopathy at intraoperative lung biopsy (p=0.021. Conclusion. Cytokines seem to be important and differentially regulated in subpopulations of young patients with cardiac shunts.

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

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N. A. Karoli

2017-01-01

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

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

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Srabani Mitra

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

Pulmonary blood flow distribution measured by radionuclide computed tomography

International Nuclear Information System (INIS)

Maeda, H.; Itoh, H.; Ishii, Y.

1982-01-01

Distributions of pulmonary blood flow per unit lung volume were measured in sitting patients with a radionuclide computed tomography (RCT) by intravenously administered Tc-99m macroaggregates of human serum albumin (MAA). Four different types of distribution were distinguished, among which a group referred as type 2 had a three zonal blood flow distribution as previously reported (West and co-workers, 1964). The pulmonary arterial pressure (Pa) and the venous pressure (Pv) were determined in this group of distribution. These values showed satifactory agreements with the pulmonary artery pressure (Par) and the capillary wedged pressure (Pcw) measured by Swan-Ganz catheter in eighteen supine patients. Those good correlations enable to establish a noninvasive methodology for measurement of pulmonary vascular pressures

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

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Jasbir D Upadhyaya

Full Text Available Activation of bitter taste receptors (T2Rs in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

Noninvasive Assisted Ventilation in Pulmonary Gas Exchange Dysfunctions in Cardiac Surgical Patients

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V. N. Poptsov

2008-01-01

Full Text Available Background. Postextubation pulmonary gas exchange dysfunctions are a potential complication in the activation of cardio-surgical patients in the early periods after surgical intervention. Objective: to evaluate the efficiency of noninvasive assisted ventilation (NIAV as a method for correcting the pulmonary gas exchange disturbances developing after early activation of cardiosurgical patients. Subjects and methods. The study included 64 patients (36 males and 28 females aged 21 to 72 (54±2 years who had been operated on under extracorporeal circulation (EC. The duration of EC and myocardial ischemia was 104±6 and 73±4 min, respectively. The indications for NIAV were the clinical manifestations of acute respiratory failure (ARF and/or PaCO2>50 mm Hg and/or PaO2/FiO2Results. During NIAV, there was improvement (p<0.05 of lung oxygenizing function (the increase in PaO2/FiO2 was 23%, a reduction in Qs/Qt from 21.1±1.9 to 13.9±1.0% (p<0.05. NIAV was accompanied by a decrease in PaCO2 (p<0.05. Hypercapnia regressed in 7 patients with isolated lung ventilatory dysfunction (PaCO2>50 mm Hg an hour after initiation of NIAV. During and after NIAV, there were reductions in right atrial pressure, mean pulmonary pressure, indexed total pulmonary vascular resistance (ITPVR (p<0.05. Prior to, during, and following NIAV, mean blood pressure, cardiac index, and indexed total pulmonary vascular resstance did not change greatly. In hypercapnia, the duration of NIAV was significantly less than that in lung oxygenizing function (2.8±0.2 hours versus 4.7±0.5 hours. That of ICU treatment was 23±4 hours. Fifty-two (81% patients were transferred from ICUs to cardiosurgical units on the following day after surgery. Conclusion. In most cases, NIAV promotes a rapid and effective correction of postextubation lung ventilatory and oxygenizing dysfunctions occurring after early activation of cardiosurgical patients. Key words: non-invasive assisted ventilation, early

Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

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Stephanie Leigh Siehr

2015-03-01

Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

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Min Yu

Full Text Available Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined.Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia.Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

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Boersma Hester

2009-04-01

Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

Update on chronic thromboembolic pulmonary hypertension.

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Robbins, Ivan M; Pugh, Meredith E; Hemnes, Anna R

2017-01-01

Chronic, unresolved thromboemboli are an important cause of pulmonary hypertension (PH) with specific treatment strategies differing from other types of PH. Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 PH by the World Health Organization. It is a rare, but underdiagnosed, complication of acute pulmonary embolism that does not resolve and results in occlusion of large pulmonary arteries with a fibro-thrombotic material. The etiology of CTEPH remains uncertain, and it is unknown why certain patients with acute pulmonary embolism develop this disorder. The evaluation for CTEPH is an important part of the evaluation for PH in general, and it is crucial not to overlook this diagnosis, as it is the only form of PH that is potentially curable. Patients diagnosed with CTEPH should be referred to an expert center for consideration of pulmonary endarterectomy, and surgical removal of the chronic thromboembolic material. Not all patients with CTEPH are surgical candidates, however, and there are emerging treatments-medical therapy and balloon pulmonary angioplasty-that have shown benefit in this patient population. Without treatment, CTEPH can lead to progressive pulmonary vascular obstruction, right heart failure, and death. Thus, it is important for clinicians to recognize this subtype of PH. In this review, we provide an overview of current understanding of the pathogenesis of CTEPH and highlight recommendations and recent advances in the evaluation and treatment of CTEPH. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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 hypertension crisis is an important complication of cardiac catheterization in pediatric IPAH. Younger age, general anesthesia, crisis history, and poor heart function are important risk factors for pulmonary hypertension crisis. PGI2 is a relatively ideal agent for

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

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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...

Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: modeling incremented pulmonary vascular resistance and heart rate.

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Vallecilla, Carolina; Khiabani, Reza H; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

2014-06-03

The considerable blood mixing in the bidirectional Glenn (BDG) physiology further limits the capacity of the single working ventricle to pump enough oxygenated blood to the circulatory system. This condition is exacerbated under severe conditions such as physical activity or high altitude. In this study, the effect of high altitude exposure on hemodynamics and ventricular function of the BDG physiology is investigated. For this purpose, a mathematical approach based on a lumped parameter model was developed to model the BDG circulation. Catheterization data from 39 BDG patients at stabilized oxygen conditions was used to determine baseline flows and pressures for the model. The effect of high altitude exposure was modeled by increasing the pulmonary vascular resistance (PVR) and heart rate (HR) in increments up to 80% and 40%, respectively. The resulting differences in vascular flows, pressures and ventricular function parameters were analyzed. By simultaneously increasing PVR and HR, significant changes (p fails to overcome the increased preload and implied low oxygenation in BDG patients at higher altitudes, especially for those with high baseline PVRs. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different PVR increments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

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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.

Pulmonary venous thrombosis secondary to radiofrequency ablation of the pulmonary veins

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Raquel López-Reyes

Full Text Available Background: Pulmonary Vein Thrombosis (PVT is a rare and underdiagnosed entity produced by local mechanical nature mechanisms, vascular torsion or direct injury to the vein. PVT has been described in clinical cases or small multicenter series mainly in relation to pulmonary vein stenosis, metastatic carcinoma, fibrosing mediastinitis, as an early surgical complication of lung transplantation lobectomy and radiofrequency ablation performed in patients with atrial fibrillation, although in some cases the cause is not known. Case: We report the case of a 57 years old male with history of atrial fibrillation treated by radiofrequency ablation who was admitted in our center because of a two-week history of consistent pleuritic pain in the left hemithorax and low-grade hemoptysis and a lung consolidation treated as a pneumonia with antibiotic but not responding to medical therapy. In view of the poor evolution of the patient, computed tomography angiography was performed with findings of PVT and secondary venous infarction and anticoagulation therapy was optimized. At the end, pulmonary resection was performed due to hemorrhagic recurrence. Conclusion: PVT remains a rare complication of radiofrequency ablation and other procedures involving pulmonary veins. Clinical suspicion and early diagnosis is crucial because is a potentially life-threatening entity. Keywords: Venous thrombosis, Atrial fibrilation, Radiofrequency ablation, Hemoptysis, Lung consolidation, Lung infarction, Lung resection surgery

Peripheral venous malformations and pulmonary hypertension: A case report and literature review

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Nambakam Tanuja Subramanyam

2015-01-01

Full Text Available Extensive pure peripheral venous malformations are rare. We report occurrence of peripheral venous malformations associated with pulmonary hypertension in a middle-aged male, who had nodular, irregular, soft, compressible, painless, non-pulsatile swellings over dependant positions such as forearms, hands, axilla, and genitalia, with overgrowth of hands and fingers enlarging slowly since early childhood. He had right ventricular failure signs. Plain films showed soft-tissue mass with diffuse calcifications (phleboliths. Doppler study showed low flow vascular channels, compressible hypoechoic lesions along with occasional hyperechoeic lesion corresponding with phleboliths. Magnetic resonance imaging (MRI, T1-weighted showed polypoidal mass with heterogenous hypo to intermediate signal with no flow voids. T2-weighted MRI showed high-signal intensity mass. Computed tomography (CT pulmonary angiogram showed pulmonary hypertension, no thrombi or vascular malformation. He was treated with angiotensin-converting enzyme inhibitors, diuretics, amiodarone, antiplatelets, and venous stockings. Specific therapy such as sclerosis and surgical resection could not be done as he was discharged against medical advice.

Pulmonary hypertension in patients with Martorell hypertensive leg ulcer: a case control study

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2012-01-01

Background Martorell hypertensive ischemic leg ulcer (Martorell ulcer) is characterized by distinct alterations in the arteriolar wall of subcutaneous vessels, leading to progressive narrowing of the vascular lumen and increase of vascular resistance. These changes are similar to the alterations observed in pulmonary arterioles in patients with chronic pulmonary hypertension (PH). This study was aimed to assess an association between the two disorders. Methods In this case–control study, 14 patients with Martorell ulcer were clinically assessed for the presence of pulmonary hypertension using transthoracic Doppler echocardiography. Data from patients were compared to 28 matched hypertensive controls. Results Systolic pulmonary arterial pressure (sPAP) in patients with Martorell ulcer was significantly higher than in the control group (33.8 ± 16.9 vs 25.3 ± 6.5 mmHg, p = 0.023); the prevalence of pulmonary hypertension was 31% (5/14) in patients and 7% (2/28) in controls (p = 0.031). No differences were seen in left heart size and function between patients and controls. Conclusion This study provides first evidence that subcutaneous arteriolosclerosis, the hallmark of Martorell ulcer, is associated with PH. These findings suggest that patients with Martorell leg ulcer might be at significant risk to develop elevated pulmonary arterial pressure. Patients with leg ulcers who present with dyspnea should be evaluated by echocardiography for the presence of pulmonary hypertension. PMID:22686459

The behaviour of the pulmonary vessels on X-ray films of children with asthma bronchiale

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Hegenbarth, R.; Toeroek, M.; Medizinische Hochschule Hannover

1986-01-01

On X-ray films of 51 children with asthma bronchiale the authors determined the vascular diameter of the right ascending pulmonary artery, the right vein of the upper lobe, and the peripheral vessels in the upper and lower pulmonary fields at an exactly defined distance from the hilus point, and compared these data with those of a control group of 143 healthy children. During the asthma attack the width of the right descending pulmonary artery and of the vein of the upper lobe corresponded to the values of the control group, whereas the vascular diameters in the upper and lower fields were clearly narrowed. Moreover, in most of the asthmatic children the authors found arc-shaped vessels and irregularly occluded vessels in the periphery of the lungs. (orig.) [de

Pulmonary function vascular index predicts prognosis in idiopathic interstitial pneumonia

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Corte, Tamera J.; Wort, Stephen J.; MacDonald, Peter S.; Edey, Anthony; Hansell, David M.; Renzoni, Elisabetta; Maher, Toby M.; Nicholson, Andrew G.; Bandula, Steven; Bresser, Paul; Wells, Athol U.

2012-01-01

Background and objective: Pulmonary hypertension (PH) is associated with increased mortality in fibrotic idiopathic interstitial pneumonia (IIP). We hypothesize that baseline KCO (diffusing capacity of carbon monoxide/alveolar volume) and 6-month decline in KCO reflect PH, thus predicting mortality

Left Ventricular Function Improves after Pulmonary Valve Replacement in Patients with Previous Right Ventricular Outflow Tract Reconstruction and Biventricular Dysfunction

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Kane, Colin; Kogon, Brian; Pernetz, Maria; McConnell, Michael; Kirshbom, Paul; Rodby, Katherine; Book, Wendy M.

2011-01-01

Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation. Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients. In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10. We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding. PMID:21720459

The cancer theory of pulmonary arterial hypertension

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Boucherat, Olivier; Vitry, Geraldine; Trinh, Isabelle; Paulin, Roxane; Provencher, Steeve; Bonnet, Sebastien

2017-01-01

Pulmonary arterial hypertension (PAH) remains a mysterious killer that, like cancer, is characterized by tremendous complexity. PAH development occurs under sustained and persistent environmental stress, such as inflammation, shear stress, pseudo-hypoxia, and more. After inducing an initial death of the endothelial cells, these environmental stresses contribute with time to the development of hyper-proliferative and apoptotic resistant clone of cells including pulmonary artery smooth muscle cells, fibroblasts, and even pulmonary artery endothelial cells allowing vascular remodeling and PAH development. Molecularly, these cells exhibit many features common to cancer cells offering the opportunity to exploit therapeutic strategies used in cancer to treat PAH. In this review, we outline the signaling pathways and mechanisms described in cancer that drive PAH cells’ survival and proliferation and discuss the therapeutic potential of antineoplastic drugs in PAH. PMID:28597757

Computer-aided detection of pulmonary embolism at CT pulmonary angiography: can it improve performance of inexperienced readers?

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Blackmon, Kevin N.; McCain, Joshua W.; Koonce, James D.; Costello, Philip; Florin, Charles; Bogoni, Luca; Salganicoff, Marcos; Lee, Heon; Bastarrika, Gorka; Thilo, Christian; Joseph Schoepf, U.

2011-01-01

To evaluate the effect of a computer-aided detection (CAD) algorithm on the performance of novice readers for detection of pulmonary embolism (PE) at CT pulmonary angiography (CTPA). We included CTPA examinations of 79 patients (50 female, 52 ± 18 years). Studies were evaluated by two independent inexperienced readers who marked all vessels containing PE. After 3 months all studies were reevaluated by the same two readers, this time aided by CAD prototype. A consensus read by three expert radiologists served as the reference standard. Statistical analysis used χ 2 and McNemar testing. Expert consensus revealed 119 PEs in 32 studies. For PE detection, the sensitivity of CAD alone was 78%. Inexperienced readers' initial interpretations had an average per-PE sensitivity of 50%, which improved to 71% (p < 0.001) with CAD as a second reader. False positives increased from 0.18 to 0.25 per study (p = 0.03). Per-study, the readers initially detected 27/32 positive studies (84%); with CAD this number increased to 29.5 studies (92%; p = 0.125). Our results suggest that CAD significantly improves the sensitivity of PE detection for inexperienced readers with a small but appreciable increase in the rate of false positives. (orig.)

Computer-aided detection of pulmonary embolism at CT pulmonary angiography: can it improve performance of inexperienced readers?

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Blackmon, Kevin N.; McCain, Joshua W.; Koonce, James D.; Costello, Philip [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Florin, Charles; Bogoni, Luca; Salganicoff, Marcos [Siemens AG, H IM SYNGO CAD Research and Development, Malvern, PA (United States); Lee, Heon [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Seoul Medical Center, Department of Radiology, Seoul (Korea, Republic of); Bastarrika, Gorka [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); University of Navarra, Department of Radiology, Pamplona (Spain); Thilo, Christian; Joseph Schoepf, U. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC (United States)

2011-06-15

To evaluate the effect of a computer-aided detection (CAD) algorithm on the performance of novice readers for detection of pulmonary embolism (PE) at CT pulmonary angiography (CTPA). We included CTPA examinations of 79 patients (50 female, 52 {+-} 18 years). Studies were evaluated by two independent inexperienced readers who marked all vessels containing PE. After 3 months all studies were reevaluated by the same two readers, this time aided by CAD prototype. A consensus read by three expert radiologists served as the reference standard. Statistical analysis used {chi}{sup 2} and McNemar testing. Expert consensus revealed 119 PEs in 32 studies. For PE detection, the sensitivity of CAD alone was 78%. Inexperienced readers' initial interpretations had an average per-PE sensitivity of 50%, which improved to 71% (p < 0.001) with CAD as a second reader. False positives increased from 0.18 to 0.25 per study (p = 0.03). Per-study, the readers initially detected 27/32 positive studies (84%); with CAD this number increased to 29.5 studies (92%; p = 0.125). Our results suggest that CAD significantly improves the sensitivity of PE detection for inexperienced readers with a small but appreciable increase in the rate of false positives. (orig.)

Systemic, pulmonary and renal haemodynamic and renal morphologic effects of intravenously infused iodixanol

International Nuclear Information System (INIS)

Sunnegaardh, O.; Hietala, S.O.; Holtz, E.; Nycomed A/S, Oslo

1990-01-01

The systemic, pulmonary and renal haemodynamic effects following an intravenous infusion (1 ml/s, 4 ml/kg) of a non-ionic isoosmolar contrast medium (iodixanol) were investigated in 8 pigs. Histopathologic changes occurring after infusion of iodixanol were studied by repeated renal biopsies. Iodixanol caused a significant increase of cardiac output, mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary arterial occlusion pressure and mean arterial pressure. There was a decrease of the systemic and pulmonary vascular resistances. Most renal biopsies showed no pathologic findings after infusion of iodixanol but in 3 specimens proteinaceous content was observed 15 min after infusion. (orig.)

Electrocautery device does not provide adequate pulmonary vessel sealing in transumbilical anatomic pulmonary lobectomy.

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Liu, Hung-Ping; Chu, Yen; Wu, Yi-Cheng; Hsieh, Ming-Ju; Liu, Chieng-Ying; Chen, Tzu-Ping; Chao, Yin-Kai; Wu, Ching-Yang; Yeh, Chi-Ju; Ko, Po-Jen; Liu, Yun-Hen

2016-05-01

Safe pulmonary vessel sealing device plays a crucial role in anatomic lung resection. In 2014, we reported high rates of massive bleeding complications during transumbilical lobectomy in a canine model due to difficulty in managing the pulmonary vessel with an endostapler. In this animal survival series, we aimed to evaluate the outcome of pulmonary vessel sealing with an electrocautery device to simplify the transumbilical thoracic surgery. Under general anesthesia, a 3-cm longitudinal incision was made over the umbilicus. Under video guidance, a bronchoscope was inserted through the incision for exploration. The diaphragmatic wound was created with an electrocautery knife and used as the entrance into the thoracic cavity. Using the transumbilical technique, anatomic lobectomy was performed with electrosurgical devices and endoscopic vascular staplers in 15 canines. Transumbilical endoscopic anatomic lobectomy was successfully completed in 12 of the 15 animals. Intraoperative bleeding developed in three animals during pulmonary hilum dissection, where one animal was killed due to hemodynamic instability and the other two animals required thoracotomy to complete the operation. There were five delayed bleeding and surgical mortality cases caused by inadequate vessel sealing by electrosurgical devices. Postmortem examination confirmed correct transumbilical lobectomy in the twelve animals that survived the operations. Transumbilical anatomic lobectomy is technically feasible in a canine model; however, the electrosurgical devices were not effective in sealing the pulmonary vessel in the current canine model.

Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists

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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.

[Thrombosis in vascular accesses for haemodialysis: rescue treatment using invasive vascular radiological techniques].

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García Medina, J; Lacasa Pérez, N; Muray Cases, S; Pérez Garrido, I; García Medina, V

2009-01-01

The purpose of this paper is to communicate our experience in the salvage of thrombosed haemodialysis vascular accesses using interventional radiology techniques. In the last four years, we have treated, by radiological means, 101 thrombosed haemodialysis vascular accesses. There were 44 autologous arteriovenous fistulas (43.56%) and 57 PTFE grafts (56.44%). There were 69 men (68.3%) and 32 women (31.7%). The mean age was 67.73 years (range 33-84). The mean vascular access age was 23.79 months (range 1-132). Manual catheter-directed aspiration was used. Fragmented, triturated or pushed the thrombus against the pulmonary circulation was avoided in all cases. 78 accesses were salvaged (77.2%). Autologous fistulas average and PTFE grafts success rate were 84.44% and 71.42% respectively. Angioplasty in one or more lesions after thromboaspiration was performed in all accesses, except six (5.9%). Metallic endoprostheses were implanted in 14 accesses (13.9%). Mean follow-up was 9 months (range 0-44). Primary patency was 42.3% +/- 5 at 6 months and 32% +/- 4 at one year. Autologous fistulas patency was better than PTFE grafts patency (p better than PTFE grafts. This justifies interventional radiology techniques in these situations.

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

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Jalpa Kotecha

2016-09-01

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

Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

Science.gov (United States)

Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

2018-01-01

Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

Use of a Smartphone for Improved Self-Management of Pulmonary Rehabilitation

Directory of Open Access Journals (Sweden)

A. Marshall

2008-01-01

Full Text Available Patients suffering from chronic respiratory disease need to follow a rehabilitative exercise programme, in order to self-manage their illness and improve quality of life. Adherence to the programme is highly dependent on professional support from a physiotherapist and hence declines when patients seek to self-manage in the home. A number of requirements were identified for a Smartphone-based application in which patients are supported remotely and given automatic feedback during exercise. An application is described which will improve adherence during pulmonary rehabilitation.

Radionuclide determined pulmonary blood volume in ischaemic heart disease

International Nuclear Information System (INIS)

Hannan, W.J.; Vojacek, J.; Connell, H.M. Dewhurst N.G.; Muir, A.L.

1981-01-01

Most measurements of pulmonary blood volume have been based on the Stewart-Hamilton dye dilution principle and have required direct catheterisation of the cardiac chambers. Alternatively a precordial counter may be used to detect the composite right and left heart curves after an intravenous injection of radionuclide. We investigated the use of a gamma camera/computer system to determine the radionuclide (sup(99m)Tc) dilution curves from individual cardiac chambers. Pulmonary transit time and pulmonary blood volume were measured in nine normal subjects, eight patients with angina pectoris but without heart failure, and 13 patients with ischaemic heart disease and left ventricular failure. Patients with heart failure had significantly greater (p 0 angle. A reduction in pulmonary blood volume in the tilted position was observed in each subject (p < 0.005). This simple non-invasive measurement should allow more detailed assessment of physiological or pharmacological changes of the pulmonary vascular bed. (author)

Rendu-Osler-Weber syndrome presenting with pulmonary arteriovenous fistula

International Nuclear Information System (INIS)

Halefoglu, A.M.

2005-01-01

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu-Osler-Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5-15% of Rendu-Osler-Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49-year-old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X-ray revealed a 5-cm mass in the left lower lobe and after magnetic resonance examination, together with 3-D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu-Osler-Weber syndrome presenting with a pulmonary arteriovenous fistula. Copyright (2005) Blackwell Science Pty Ltd

Changes in perfusion scintigraphy in the first days of heparin therapy in patients with acute pulmonary embolism

NARCIS (Netherlands)

de Groot, M. R.; Oostdijk, A. H.; Engelage, A. H.; van Marwijk Kooy, M.; Büller, H. R.

2000-01-01

Patients with suspected pulmonary embolism often receive heparin therapy for hours to days before ventilation/perfusion scintigraphy is completed. We assessed to what extent the lung scan classification and pulmonary vascular perfusion changed over a period of 2-4 days of full anticoagulant therapy.

Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

Science.gov (United States)

Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

2013-06-01

The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

Science.gov (United States)

Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

2017-11-01

To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

Science.gov (United States)

Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

2015-02-01

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Single photon emission computed tomography study of human pulmonary perfusion: preliminary findings

Energy Technology Data Exchange (ETDEWEB)

Carratu, L; Sofia, M [Naples Univ. (Italy). Facolta di Medicina e Chirurgia; Salvatore, M; Muto, P; Ariemma, G [Istituto Nazionale per la Prevenzione, Lo Studio e La Cura dei Tumori Fondazione Pascale, Naples (Italy); Lopez-Majano, V [Cook County Hospital, Chicago, IL (USA). Nuclear Medicine Div.

1984-02-01

Single photon emission computed tomography (SPECT) was performed with /sup 99/Tcsup(m)-albumin macroaggregates to study human pulmonary perfusion in healthy subjects and patients with respiratory diseases such as chronic obstructive pulmonary disease (COPD) and lung neoplasms. The reconstructed SPECT data was displayed in coronal, transverse, sagittal plane sections and compared to conventional perfusion scans. The SPECT data gave more complicated anatomical information about the extent of damage and morphology of the pulmonary vascular bed. In healthy subjects and COPD patients, qualitative and quantitative assessment of pulmonary perfusion could be obtained from serial SPECT scans with respect to distribution and relative concentration of the injected radiopharmaceutical. Furthermore, SPECT of pulmonary perfusion has been useful in detecting the extent of damage to the pulmonary circulation. This is useful for the preoperative evaluation and staging of lung cancer.

Commentary on: "Vascular distensibilities have minor effects on intracardiac shunt patterns in reptiles" by Filogonio et al. (2017).

Science.gov (United States)

Hillman, Stanley S; Hedrick, Michael S; Kohl, Zachary F

2017-06-01

The recent study by Filogonio et al. (2017) suggested that net cardiac shunt patterns in two species of reptiles (Trachemys scripta and Crotalus durissus) were not significantly influenced by the vascular distensibilities of the systemic and pulmonary vasculatures. This is in contrast to a previously published study (Hillman et al., 2014) in the toad (Rhinella marina) in which net cardiac shunts were predicted primarily by the physical properties of vascular distensibility rather than physiological control of resistance of the systemic and pulmonary vasculature. We analyze the data and conclusions reached by Filogonio et al. (2017) regarding the role of vascular distensibilities in determining net cardiac shunt patterns in reptiles in comparison with toads. In our view, the conclusions reached by Filogonio et al. (2017) are not supported by the data primarily because vascular distensibilities were not measured in the reptiles analyzed in their study. Copyright © 2017 Elsevier GmbH. All rights reserved.

Correlation of plasma endothelin-1 levels with pulmonary hypertension after inhaled nitric oxide therapy

International Nuclear Information System (INIS)

Razzaq, Z.; Naqvi, S.; Aslam, M.

2009-01-01

Variable response to inhaled nitric oxide (iNO) therapy in patients with mitral stenosis (MS) having pulmonary hypertension (PH) has been documented in early studies. The objectives of this study were to measure plasma Endothelin-1 (ET-1) levels in those patients and to correlate them with pulmonary vascular indices after iNO therapy. It was Quesi-experimental study. Methods: Thirty patients with mitral or mixed mitral and aortic valve disease with severe pulmonary hypertension and enrolled for valve replacement surgery were included. Before the replacement, baseline pulmonary vascular indices and cardiac output were recorded. After the surgery, 10 - 20 was in administered for 1 hour and all the parameters were again recorded. Patients were grouped into responders and non responders on the basis of % reduction in Pulmonary Vascular Resistance (PVR) after iNO therapy. Plasma ET-1 levels were measured in both groups by ELISA before and after the iNO therapy. Paired sample t-test was used to compare mean values for significance. The correlations between variables were then calculated by using Pearson's coefficient. Results: The plasma ET-1 levels were very high in all patients. They reduced in responders after iNO therapy; non-responders paradoxically showed significant increase in the levels of ET-1 after iNO therapy. Moreover, a positive correlation was observed in plasma ET-1 levels and post operative levels of PVR. Conclusion: The correlation of changes in PVR and plasma ET-1 levels in responders suggests that high plasma ET-1 is a key mediator of poor response in PH secondary to MS, after iNO therapy. (author)

Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: New Horizons in the Interventional Management of Pulmonary Embolism.

Science.gov (United States)

Rivers-Bowerman, Michael D; Zener, Rebecca; Jaberi, Arash; de Perrot, Marc; Granton, John; Moriarty, John M; Tan, Kong T

2017-09-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed potential complication of acute or recurrent pulmonary thromboembolic disease. Multiple studies suggest that up to 5% of patients with acute pulmonary thromboembolic disease go on to develop CTEPH. The prognosis of untreated CTEPH is poor, but advances in medical and surgical treatments over the past few decades have improved patient outcomes. The gold standard and curative treatment for CTEPH is pulmonary endarterectomy; however, some patients are inoperable and others who have undergone pulmonary endarterectomy experience persistent or recurrent pulmonary hypertension despite medical therapy. In recent years, balloon pulmonary angioplasty has emerged as a primary and adjunctive treatment for these CTEPH patients at expert or specialized centers. This review outlines an approach to balloon pulmonary angioplasty for CTEPH, including clinical presentation and evaluation; patient selection and indications; treatment planning; equipment and technique; overcoming technical challenges; recognition and management of complications; postprocedural care and clinical follow-up; and expected outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the relationship between radiological abnormalities and both pulmonary function and pulmonary hypertension in coal workers' pneumoconiosis

Energy Technology Data Exchange (ETDEWEB)

Yildiz, O.A.; Gulbay, B.E.; Saryal, S.; Karabiylkoglu, G. [Ankara University, Ankara (Turkey). School of Medicine

2007-05-15

The aim of this study was to investigate the effect of the radiological evidence of emphysema, and the extent of interstitial involvement, on lung function and pulmonary arterial pressure (PAP) in patients with coal workers' pneumoconiosis (CWP). All patients showed a mild decrease in FEV1/FVC and a mild increase in FRC. Forty-four per cent of patients developed mild to moderate pulmonary hypertension. Emphysema scores correlated significantly with airflow rates, including FEV1%, FEV1/FVC and FEF25-75%, and with carbon monoxide diffusing capacity (DLCO)% predicted as well as FRC% predicted and the ratio RV/TLC, which are indices of air trapping. Additionally, profusion and global profusion scores showed significant correlation with FEV1/FVC, DLCO% predicted, specific airway conductance and smoking. Mean PAP showed a significant negative correlation with FEF50% predicted, DLCO% predicted and profusion score. The impairment of pulmonary function (mainly disturbance in airflow rates and air trapping) and pulmonary hypertension may be present, even in a simple form of CWP. The pulmonary function impairment in patients with CWP is likely to be attributable to the occurrence of emphysema. However, pulmonary hypertension was directly related to the profusion of pneumoconiotic nodules, which may result in obliteration of the vascular bed.

The pathophysiology of chronic thromboembolic pulmonary hypertension

Directory of Open Access Journals (Sweden)

Gérald Simonneau

2017-03-01

Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.

Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

Science.gov (United States)

Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi

2012-01-01

Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.

Effects of posture on postoperative pulmonary function

DEFF Research Database (Denmark)