[Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema].

PubMed

Casas, Juan Pablo; Abbona, Horacio; Robles, Adriana; López, Ana María

2008-01-01

Pulmonary function tests in idiopathic pulmonary fibrosis characteristically show a restrictive pattern, resulting from reduction of pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

Connective tissue disease-associated pulmonary arterial hypertension

PubMed Central

Howard, Luke S.

2015-01-01

Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension

PubMed Central

Woods, Crystal; Stearman, Robert S.; Venkataraman, Sujatha; Ferguson, Bradley S.; Swain, Kalin; Bowler, Russell P.; Geraci, Mark W.; Ihida-Stansbury, Kaori; Stenmark, Kurt R.; McKinsey, Timothy A.; Domann, Frederick E.

2016-01-01

Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2′-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression. PMID:27233998

Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: determinants and impact on pump function.

PubMed

Badagliacca, Roberto; Poscia, Roberto; Pezzuto, Beatrice; Papa, Silvia; Gambardella, Cristina; Francone, Marco; Mezzapesa, Mario; Nocioni, Martina; Nona, Alfred; Rosati, Riccardo; Sciomer, Susanna; Fedele, Francesco; Dario Vizza, Carmine

2015-03-01

Right ventricular (RV) dyssynchrony has been described in pulmonary arterial hypertension (PAH), but no evidence is available on its morphologic determinants and its effect on systolic function. The aim of this study was to evaluate the morphologic determinants of RV dyssynchrony by echocardiographic and cardiac magnetic resonance imaging and its effect on systolic function. In 60 consecutive idiopathic PAH (IPAH) patients with narrow QRS, RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography, calculating the standard deviation of the times to peak systolic strain for the four mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV-SD4 (19 milliseconds) and compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Despite similar pulmonary vascular resistance and mean pulmonary arterial pressure, patients with RV-SD4 at >19 milliseconds had advanced WHO class and worse 6MWT, RV hemodynamics, RV remodeling and systolic function parameters compared with patients at ≤19 milliseconds. The morphologic determinants of RV dyssynchrony resulted RV end-diastolic area, LV diastolic eccentricity index and RV mass volume ratio (r = 0.69, r(2) = 0.47, p < 0.0001). Finally, we found a significant inverse correlation between RV mid-basal segments post-systolic shortening time and cardiac index (r = -0.64, r(2) = 0.41, p = 0.001), accounting for the significant correlation between RV-SD4 and cardiac index (r = 0.57, r(2) = 0.32, p = 0.003). In IPAH with narrow QRS, RV dyssynchrony is associated with RV dilation and eccentric hypertrophy pattern, suggesting a role of segmental wall stress heterogeneity as the major determinant of mechanical delay. Post-systolic shortening, as inefficient contraction, contributes to pump dysfunction. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Pregnancy in pulmonary arterial hypertension patients].

PubMed

Rosengarten, Dror; Kramer, Mordechai R

2013-09-01

Pulmonary arterial hypertension (PAH) is a disorder defined by elevated mean pulmonary arterial pressure. PAH can be idiopathic or associated with a variety of medical conditions such as scleroderma, congenital heart disease, left heart failure, lung disease or chronic pulmonary thromboembolism. This progressive disease can cause severe right heart failure and death. Normal physiologic changes that occur during pregnancy may produce fatal consequences in PAH patients. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. During the past decade, new advanced therapies for PAH have emerged gathering reports of successful pregnancies in patients with pulmonary hypertension. Substantial risk still exists and current recommendations have not changed. Nevertheless, in selected cases, if a patient insists on continuing the pregnancy, being fully aware of the risks involved, an intensive treatment approach should be implemented in experienced centers. This is necessary in order to control pulmonary hypertension during pregnancy and reduce the risk so as to improve outcomes. This review will focus on the pathophysiology of PAH in pregnancy and appropriate management during pregnancy, delivery and the post-partum period.

Idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Mycotic pulmonary artery aneurysm following pulmonary artery banding.

PubMed

Kumar, R V; Roughneen, P T; de Leval, M R

1994-01-01

A neonate with situs inversus, transposition of the great arteries, ventricular septal defect, criss-cross ventricles and hypoplastic right ventricle underwent pulmonary artery banding at the age of 7 days. The course was complicated by septicaemia and subsequently the development of an aneurysm of the pulmonary artery. Serratia marcessans was grown from the band site. The pulmonary artery aneurysm was resected and the pulmonary artery was repaired. The literature is reviewed with the emphasis on diagnosis, natural history and surgical management.

O-linked β-N-acetylglucosamine transferase directs cell proliferation in idiopathic pulmonary arterial hypertension.

PubMed

Barnes, Jarrod W; Tian, Liping; Heresi, Gustavo A; Farver, Carol F; Asosingh, Kewal; Comhair, Suzy A A; Aulak, Kulwant S; Dweik, Raed A

2015-04-07

Idiopathic pulmonary arterial hypertension (IPAH) is a cardiopulmonary disease characterized by cellular proliferation and vascular remodeling. A more recently recognized characteristic of the disease is the dysregulation of glucose metabolism. The primary link between altered glucose metabolism and cell proliferation in IPAH has not been elucidated. We aimed to determine the relationship between glucose metabolism and smooth muscle cell proliferation in IPAH. Human IPAH and control patient lung tissues and pulmonary artery smooth muscle cells (PASMCs) were used to analyze a specific pathway of glucose metabolism, the hexosamine biosynthetic pathway. We measured the levels of O-linked β-N-acetylglucosamine modification, O-linked β-N-acetylglucosamine transferase (OGT), and O-linked β-N-acetylglucosamine hydrolase in control and IPAH cells and tissues. Our data suggest that the activation of the hexosamine biosynthetic pathway directly increased OGT levels and activity, triggering changes in glycosylation and PASMC proliferation. Partial knockdown of OGT in IPAH PASMCs resulted in reduced global O-linked β-N-acetylglucosamine modification levels and abrogated PASMC proliferation. The increased proliferation observed in IPAH PASMCs was directly impacted by proteolytic activation of the cell cycle regulator, host cell factor-1. Our data demonstrate that hexosamine biosynthetic pathway flux is increased in IPAH and drives OGT-facilitated PASMC proliferation through specific proteolysis and direct activation of host cell factor-1. These findings establish a novel regulatory role for OGT in IPAH, shed a new light on our understanding of the disease pathobiology, and provide opportunities to design novel therapeutic strategies for IPAH. © 2015 American Heart Association, Inc.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand.

PubMed

Strange, Geoff; Lau, Edmund M; Giannoulatou, Eleni; Corrigan, Carolyn; Kotlyar, Eugene; Kermeen, Fiona; Williams, Trevor; Celermajer, David S; Dwyer, Nathan; Whitford, Helen; Wrobel, Jeremy P; Feenstra, John; Lavender, Melanie; Whyte, Kenneth; Collins, Nicholas; Steele, Peter; Proudman, Susanna; Thakkar, Vivek; Keating, Dominic; Keogh, Anne

2017-09-20

Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland.

PubMed

Ling, Yi; Johnson, Martin K; Kiely, David G; Condliffe, Robin; Elliot, Charlie A; Gibbs, J Simon R; Howard, Luke S; Pepke-Zaba, Joanna; Sheares, Karen K K; Corris, Paul A; Fisher, Andrew J; Lordan, James L; Gaine, Sean; Coghlan, J Gerry; Wort, S John; Gatzoulis, Michael A; Peacock, Andrew J

2012-10-15

Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease. To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland. All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively. A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacity of carbon monoxide, more severe hemodynamic impairment, but better survival compared with older patients. In comparison with the earlier cohorts, patients diagnosed in 2007-2009 were older, more obese, had lower percent diffusing capacity of carbon monoxide,(,) and more comorbidities, but better survival. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) equation, REVEAL risk score, and Pulmonary Hypertension Connection Registry survival equation accurately predicted survival of our incident cohort at 1 year. This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities.

Idiopathic infantile arterial calcification in two siblings: failure of treatment with diphosphonate.

PubMed Central

Stuart, G; Wren, C; Bain, H

1990-01-01

Two siblings with idiopathic infantile arterial calcification are reported. The fetal and postnatal echocardiographic features were a large pericardial effusion, thickened pulmonary and aortic valves, poor pulsation of the descending aorta, and calcification of the great vessels. In one patient calcification was first detected at 33 weeks' gestation. Despite treatment with disodium etidronate both children died. Images PMID:2118367

Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p < 0.001) and severe PH (HR 2.068, 95% CI: 1.715 to 2.493, p < 0.001). Further assessment by multivariate Cox models identified significant risk for death for mild PH (HR 1.433, 95% CI: 1.203 to 1.706, p < 0.001) and severe PH (HR 1.597, 95% CI: 1.308 to 1.949, p < 0.001). Propensity score matching confirmed the risk for death for mild PH (HR 1.530, 95% CI: 1.189 to 1.969, p = 0.001) and severe PH (HR 2.103, 95% CI: 1.436 to 3.078, p < 0.001). The manifestation of PH, even with mild severity, is associated with significantly increased risk for death among patients with idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.

PubMed

Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed

2016-01-01

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.

Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.

PubMed

Overbeek, Maria J; Boonstra, Anco; Voskuyl, Alexandre E; Vonk, Madelon C; Vonk-Noordegraaf, Anton; van Berkel, Maria P A; Mooi, Wolter J; Dijkmans, Ben A C; Hondema, Laurens S; Smit, Egbert F; Grünberg, Katrien

2011-04-14

Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation. Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity. All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals. PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity

Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report.

PubMed

Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio

2016-05-25

Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Effects of exercise training in patients with idiopathic pulmonary arterial hypertension.

PubMed

de Man, F S; Handoko, M L; Groepenhoff, H; van 't Hul, A J; Abbink, J; Koppers, R J H; Grotjohan, H P; Twisk, J W R; Bogaard, H-J; Boonstra, A; Postmus, P E; Westerhof, N; van der Laarse, W J; Vonk-Noordegraaf, A

2009-09-01

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained. 6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32+/-5 to 46+/-6 W; p = 0.003) together with an increase in exercise endurance time (p<0.001). Moreover, exercise training increased quadriceps strength by 13% (p = 0.005) and quadriceps endurance by 34% (p = 0.001). Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36+/-0.10 to 1.78+/-0.13 capillaries per muscle fibre; p<0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution. Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

ClinicalTrials.gov

2018-06-08

Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension.

PubMed

Cheng, Xiao-Ling; He, Jian-Guo; Liu, Zhi-Hong; Gu, Qing; Ni, Xin-Hai; Zhao, Zhi-Hui; Luo, Qin; Xiong, Chang-Ming

2017-02-01

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH). 194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH. Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = -0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = -0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan-Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001). Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

PubMed Central

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.

1990-05-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is oftenmore » needed for accurate differential diagnosis.« less

Pulmonary arterial hypertension

PubMed Central

2013-01-01

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension.

PubMed

Chaouat, Ari; Sitbon, Olivier; Mercy, Magalie; Ponçot-Mongars, Raphaëlle; Provencher, Steeve; Guillaumot, Anne; Gomez, Emmanuel; Selton-Suty, Christine; Malvestio, Pascale; Regent, Denis; Paris, Christophe; Hervé, Philippe; Chabot, François

2014-09-01

The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. ©ERS 2014.

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

PubMed Central

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

2012-01-01

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

Update on diagnosis and treatment of idiopathic pulmonary fibrosis

PubMed Central

Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

2015-01-01

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

PubMed Central

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

Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management

PubMed Central

Oldham, Justin M.; Collard, Harold R.

2017-01-01

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3–5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH), while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM) and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the

Pulmonary arterial hypertension in pregnancy.

PubMed

Običan, Sarah G; Cleary, Kirsten L

2014-08-01

Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute effects of exercise on the inflammatory state in patients with idiopathic pulmonary arterial hypertension.

PubMed

Harbaum, Lars; Renk, Emilia; Yousef, Sara; Glatzel, Antonia; Lüneburg, Nicole; Hennigs, Jan K; Oqueka, Tim; Baumann, Hans J; Atanackovic, Djordje; Grünig, Ekkehard; Böger, Rainer H; Bokemeyer, Carsten; Klose, Hans

2016-11-11

Exercise training positively influences exercise tolerance and functional capacity of patients with idiopathic pulmonary arterial hypertension (IPAH). However, the underlying mechanisms are unclear. We hypothesized that exercise modulates the activated inflammatory state found in IPAH patients. Single cardiopulmonary exercise testing was performed in 16 IPAH patients and 10 healthy subjects. Phenotypic characterization of peripheral blood mononuclear cells and circulating cytokines were assessed before, directly after and 1 h after exercise. Before exercise testing, IPAH patients showed elevated Th2 lymphocytes, regulatory T lymphocytes, IL-6, and TNF-alpha, whilst Th1/Th17 lymphocytes and IL-4 were reduced. In IPAH patients but not in healthy subject, exercise caused an immediate relative decrease of Th17 lymphocytes and a sustained reduction of IL-1-beta and IL-6. The higher the decrease of IL-6 the higher was the peak oxygen consumption of IPAH patients. Exercise seems to be safe from an immune and inflammatory point of view in IPAH patients. Our results demonstrate that exercise does not aggravate the inflammatory state and seems to elicit an immune-modulating effect in IPAH patients.

Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: The delay study

PubMed Central

Strange, Geoff; Gabbay, Eli; Kermeen, Fiona; Williams, Trevor; Carrington, Melinda; Stewart, Simon; Keogh, Anne

2013-01-01

Survival rates for patients with idiopathic pulmonary arterial hypertension (IPAH) have improved with the introduction of PAH-specific therapies. However, the time between patient-reported onset of symptoms and a definitive diagnosis of IPAH is consistently delayed. We conducted a retrospective, multi-center, descriptive investigation in order to (a) understand what factors contribute to persistent diagnostic delays, and (b) examine the time from initial symptom onset to a definitive diagnosis of IPAH. Between January 2007 and December 2008, we enrolled consecutively diagnosed adults with IPAH from four tertiary referral centers in Australia. Screening of patient records and “one-on-one” interviews were used to determine the time from patient-described initial symptoms to a diagnosis of IPAH, confirmed by right heart catheterization (RHC). Thirty-two participants (69% female) were studied. Mean age at symptom onset was 56 ± 16.4 years and 96% reported exertional dyspnea. Mean time from symptom onset to diagnosis was 47 ± 34 months with patients subsequently aged 60 ± 17.3 years. Patients reported 5.3 ± 3.8 GP visits and 3.0 ± 2.1 specialist reviews before being seen at a pulmonary hypertension (PH) center. Advanced age, number of general practitioner (GP) visits, heart rate, and systolic blood pressure at the time of diagnosis were significantly associated with the observed delay. We found a significant delay of 3.9 years from symptom onset to a diagnosis of IPAH in Australia. Exertional dyspnea is the most common presenting symptom. Current practice within Australia does not appear to have the specific capacity for timely, multi-factorial evaluation of breathlessness and potential IPAH. PMID:23662179

Selective Arterial Embolization of Idiopathic Priapism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, Gary S.; Braunstein, Larry; Ball, David S.

1996-11-15

We report a case of idiopathic priapism that was only identified as high-flow or arterial priapism after drainage of the corpora cavernosa. Following failure of conservative and surgical treatment attempts, two consecutive embolizations of a unilateral penile artery were performed with gelgoam particles.

From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis.

PubMed

Strock, Stephen B; Alder, Jonathan K; Kass, Daniel J

2018-04-01

Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Genetics Home Reference: idiopathic pulmonary fibrosis

MedlinePlus

... structures at the ends of chromosomes known as telomeres . It is not well understood how defects in ... Collard HR, Wolters PJ, Garcia CK. Effect of telomere length on survival in patients with idiopathic pulmonary ...

Idiopathic pulmonary fibrosis: evolving concepts.

PubMed

Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

2014-08-01

Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Pulmonary Arterial Hypertension

MedlinePlus

Pulmonary Arterial Hypertension What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout your body. While the heart is one organ, it ...

Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels.

PubMed

Strielkov, Ievgen; Krause, Nicole Catherine; Sommer, Natasha; Schermuly, Ralph Theo; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Gudermann, Thomas; Dietrich, Alexander; Weissmann, Norbert

2018-06-19

What is the central question of this study? Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail. What is the main finding and its importance? We found that only small intrapulmonary arteries (80 - 200 μm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization-induced preconstriction, and not dependent on endothelium and TRPC6 channels. Hypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. Properties of hypoxic pulmonary vasoconstriction (HPV) vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. We investigated the effect of 80-min exposure to hypoxia on tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction using wire myography. Hypoxia induced a sustained relaxation in non-preconstricted extrapulmonary arteries (500 - 700 μm in diameter), but not in the presence of KCl-induced preconstriction. Large intrapulmonary arteries (450 - 650 μm) did not exhibit a significant response to the hypoxic challenge. By contrast, in small intrapulmonary arteries (80 - 200 μm), hypoxia elicited a slowly developing sustained constriction, which was independent of endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. HPV was not altered in pulmonary arteries of TRPC6-deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer-perfused, and ventilated mouse lungs. In conclusion, we have established the protocol allowing to study sustained HPV in isolated mouse pulmonary arteries. The

Increased CD39 Nucleotidase Activity on Microparticles from Patients with Idiopathic Pulmonary Arterial Hypertension

PubMed Central

Visovatti, Scott H.; Hyman, Matthew C.; Bouis, Diane; Neubig, Richard; McLaughlin, Vallerie V.; Pinsky, David J.

2012-01-01

Background Idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease. Methodology/ Principal Findings Kinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b−) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased. Conclusions/ Significance We demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH. PMID:22792409

The Prognostic Value of 18F-FDG Uptake Ratio Between the Right and Left Ventricles in Idiopathic Pulmonary Arterial Hypertension.

PubMed

Li, Wen; Wang, Lei; Xiong, Chang-Ming; Yang, Tao; Zhang, Yan; Gu, Qing; Yang, Yong; Ni, Xin-Hai; Liu, Zhi-Hong; Fang, Wei; He, Jian-Guo

2015-11-01

Metabolic changes occur in the right ventricle (RV) under increased afterload in pulmonary arterial hypertension. FDG PET imaging has potential to assess RV function. In this study, we aimed to determine the prognostic value of metabolic changes of RV using FDG PET imaging in idiopathic pulmonary arterial hypertension (IPAH). In this prospective investigation, patients newly diagnosed with IPAH were recruited. Patients underwent right heart catheterization, FDG PET imaging, and cardiac MR (CMR) within 1 week. Right ventricle hemodynamics, glucose metabolism derived from the FDG uptake levels, and functional parameters were obtained. The FDG uptake ratio between the RV and the left ventricle (LV) and its relation with the patients' survival were analyzed. A total of 45 IPAH patients were enrolled in this study, which included 13 male (28.9%) and 32 female (71.1%). The median follow-up time of this study was 1043 days. At the end of the follow-up, 36 patients survived, whereas 9 patients were deceased because of right heart failure. Multivariate Cox proportional hazard analysis showed that the ratio between the corrected RV and LV FDG uptake (cRV/LV) in both glucose-loading (cRV/LVg) and fasting (cRV/LVf) conditions independently predicted the mortality after adjusting for pulmonary vascular resistance index, mean right atrial pressure, and World Health Organization functional class. Kaplan-Meier survival analysis showed that patients with cRV/LVf greater than 143.65% in fasting condition (log rank, P = 0.030) or cRV/LVg greater than 120.55% in glucose-loading condition (log rank, P = 0.014) had worse prognosis. The FDG uptake ratio between the RV and LV can be an independent predictor for long-term prognosis of IPAH patients.

Update in pulmonary arterial hypertension.

PubMed

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

2016-11-01

Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Factors affecting the response to exercise in patients with severe pulmonary arterial hypertension.

PubMed

Flox-Camacho, Angela; Escribano-Subías, Pilar; Jiménez-López Guarch, Carmen; Fernández-Vaquero, Almudena; Martín-Ríos, Dolores; de la Calzada-Campo, Carlos Sáenz

2011-01-01

Ergospirometry objectively quantifies exercise capacity. Up until now, the response to exercise evaluated by ergospirometry in patients with pulmonary arterial hypertension has only been described in recently diagnosed.patients. Our aim is to describe the response to exercise in patients with severe pulmonary arterial hypertension under specific treatment and define which parameters determine their exercise capacity. A cross-sectional study was performed on 80 patients, 57 women, aged 45 (14), with severe pulmonary arterial hypertension (48 idiopathic, 14 related to toxic rapeseed oil, 13 to connective tissue disease, 5 to human immunodeficiency virus), mean pulmonary pressure at diagnosis 61(15)mmHg and after 49(33) months under treatment since diagnosis. Biomarkers were measured and echocardiography and ergospirometry were performed the same day. Our patients, under specific treatment, showed the typical behaviour of patients with pulmonary arterial hypertension with less limitation of both aerobic capacity and ventilatory efficiency. Being male (p=0.004), high ventilatory equivalent for carbon dioxide at anaerobic threshold (p<0.001) or biomarkers (p=0.006) were the strongest predictors of impaired peak oxygen uptake in multivariate analysis, whereas for an impaired percentage achieved of predicted value were right ventricle diastolic diameter (p<0.001), months of treatment (p=0.01) and high ventilatory equivalent for CO(2) (p<0.001). In pulmonary arterial hypertension, right ventricle dysfunction (expressed by its dilation or high NTproBNP) and impaired ventilatory inefficiency as well as being male or a short time under treatment can be considered as determining factors of impaired exercise capacity. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype

PubMed Central

Allen, Roblee P.; Schelegle, Edward S.

2014-01-01

Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2−n/X and the arterial area ratio β = 21–2/X. Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process. PMID:24858853

Genetics Home Reference: pulmonary arterial hypertension

MedlinePlus

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

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

PubMed

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; P<0.0001) compared with PA from control subjects (n=10). PA remodelling was evaluated in human pulmonary 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.

Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

NASA Astrophysics Data System (ADS)

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

2008-03-01

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

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

PubMed

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.

Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil.

PubMed

Ascha, Mona; Zhou, Xuan; Rao, Youlan; Minai, Omar A; Tonelli, Adriano R

2017-10-01

Anticoagulation is a common treatment modality in patients with pulmonary arterial hypertension (PAH). Further studies are needed to appropriately assess the risk/benefit ratio of anticoagulation, particularly in PAH patients receiving PAH-specific therapies. We use observational long-term data on PAH patients treated with subcutaneous (SQ) treprostinil from a large open-label study. Patients were followed for up to 4 years. The use of warfarin and bleeding events were recorded. At total of 860 patients (age [mean±SD] 46±15 years, 76% female, 83% Caucasian, 49% idiopathic PAH, and 76% New York Heart Association [NYHA] functional class III) were included. All patients received SQ treprostinil (15% also other pulmonary hypertension [PH]-therapies) and 590 (69%) received warfarin during the study. The proportions of women, African American, and idiopathic pulmonary hypertension (IPAH) patients were higher in the group receiving warfarin. A higher proportion of patients with congenital heart disease and portopulmonary hypertension did not receive warfarin. There were no differences in unadjusted long-term survival between PAH patients receiving warfarin or not (log-rank test, P value=.69), even when only considering idiopathic PAH (P=.32). In addition, no difference was found in adjusted long-term survival both in PAH (P=.84) and idiopathic PAH patients (P=.44) based on the use of warfarin. Furthermore, no survival difference based on the use of warfarin were noted between propensity score-matched PAH patients (P=.37). Long-term anticoagulation with warfarin was not associated with any significant effect on survival in PAH or idiopathic PAH patients treated with SQ treprostinil. © 2017 John Wiley & Sons Ltd.

Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

PubMed Central

Kimura, Yukiko; Weiss, Jennifer E.; Haroldson, Kathryn L.; Lee, Tzielan; Punaro, Marilynn; Oliveira, Sheila; Rabinovich, Egla; Riebschleger, Meredith; Antón, Jordi; Blier, Peter R.; Gerloni, Valeria; Hazen, Melissa M; Kessler, Elizabeth; Onel, Karen; Passo, Murray H; Rennebohm, Robert M; Wallace, Carol A; Woo, Patricia; Wulffraat, Nico

2015-01-01

Objectives Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear effective. Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency. Our aim was to characterize and compare these cases to a larger cohort of sJIA patients. Methods sJIA patients who developed PAH, ILD and/or AP were identified through an electronic listserv, and their demographic, sJIA and pulmonary disease characteristics, and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Results Patients (N=25) were significantly (p<0.05) more likely than the CARRA registry cohort (N=389) to be female, have more systemic features, and to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide. Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 15 (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 AP and 7 ILD. Seventeen (68%) patients were taking or recently (≤1 month) discontinued a biologic agent at pulmonary symptom onset; 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 8.8 months from pulmonary diagnosis. Conclusions PAH, AP and ILD are under-recognized complications of sJIA which are frequently fatal. These may be the result of severe uncontrolled systemic disease activity, and may be influenced by medication exposure. PMID:23139240

Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations

PubMed Central

Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

2016-01-01

Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060

Stretch-induced contraction in pulmonary arteries.

PubMed

Kulik, T J; Evans, J N; Gamble, W J

1988-12-01

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.

Coronary artery to pulmonary artery fistula.

PubMed

Dadkhah-Tirani, Heidar; Salari, Arsalan; Shafighnia, Shora; Hosseini, Seyed Fazel; Naghdipoor, Misa

2013-01-01

Male, 69 FINAL DIAGNOSIS: Coronary artery to pulmonary artery fistula Symptoms: Chest pain Medication: - Clinical Procedure: Echocardiography • angiography • surgical intervention Specialty: Cardiology • Cardiac Surgery. Rare disease. A coronary artery fistula is an abnormal communication between a coronary artery and one of the cardiac chambers or a great vessel, so bypassing the myocardial capillary network. They are usually discovered incidentally upon coronary angiography. Clinical manifestations are variable depending on the type of fistula, the severity of shunt, site of shunt, and presence of other cardiac condition. We report a 69-year-old man without any previous medical history, who was admitted to our hospital with chest pain. The electrocardiogram (ECG) showed a sinus rhythm with ST depression in V2 to V6 precordial leads. Coronary angiography revealed a coronary artery fistula from left anterior descending coronary artery (LAD) to the main pulmonary artery, right coronary artery blockage and significant stenoses on the LAD and left circumflex artery (LCX). Surgical treatment was chosen because of the total occlusion of the right coronary artery and to relieve of pain to improve quality of life.

Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression

PubMed Central

Tsai, Ben M.; Lahm, Tim; Morrell, Eric D.; Crisostomo, Paul R.; Markel, Troy; Wang, Meijing; Meldrum, Daniel R.

2009-01-01

Hypoxic pulmonary vasoconstriction is a common consequence of acute lung injury and may be mediated by increased local production of proinflammatory cytokines. Ethyl pyruvate is a novel anti-inflammatory agent that has been shown to downregulate proinflammatory genes following hemorrhagic shock; however, its effects on hypoxic pulmonary vasoconstriction are unknown. We hypothesized that ethyl pyruvate would inhibit hypoxic pulmonary vasoconstriction and downregulate pulmonary artery cytokine expression during hypoxia. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings (n=8/group) during hypoxia (95% N2/5% CO2) with or without prior ethyl pyruvate (10 mM) treatment. Following 60 minutes of hypoxia, pulmonary artery rings were analyzed for TNF-α and IL-1 mRNA via RT-PCR. Ethyl pyruvate inhibited hypoxic pulmonary artery contraction (4.49±2.32% vs. 88.80±5.68% hypoxia alone) and attenuated the hypoxic upregulation of pulmonary artery TNF and IL-1 mRNA (p<0.05). These data indicate that: 1) hypoxia increases pulmonary artery vasoconstriction and proinflammatory cytokine gene expression; 2) ethyl pyruvate decreases hypoxic pulmonary vasoconstriction and downregulates hypoxia-induced pulmonary artery proinflammatory cytokine gene expression; and 3) ethyl pyruvate may represent a novel therapeutic adjunct in the treatment of acute lung injury. PMID:17574585

Validation of a Method To Screen for Pulmonary Hypertension in Advanced Idiopathic Pulmonary Fibrosis*

PubMed Central

Zisman, David A.; Karlamangla, Arun S.; Kawut, Steven M.; Shlobin, Oksana A.; Saggar, Rajeev; Ross, David J.; Schwarz, Marvin I.; Belperio, John A.; Ardehali, Abbas; Lynch, Joseph P.; Nathan, Steven D.

2008-01-01

Background We have developed a method to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients, based on a formula to predict mean pulmonary artery pressure (MPAP) from standard lung function measurements. The objective of this study was to validate this method in a separate group of IPF patients. Methods Cross-sectional study of 60 IPF patients from two institutions. The accuracy of the MPAP estimation was assessed by examining the correlation between the predicted and measured MPAPs and the magnitude of the estimation error. The discriminatory ability of the method for PH was assessed using the area under the receiver operating characteristic curve (AUC). Results There was strong correlation in the expected direction between the predicted and measured MPAPs (r = 0.72; p < 0.0001). The estimated MPAP was within 5 mm Hg of the measured MPAP 72% of the time. The AUC for predicting PH was 0.85, and did not differ by institution. A formula-predicted MPAP > 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 95%, 58%, 51%, and 96%, respectively, for PH defined as MPAP from right-heart catheterization > 25 mm Hg. Conclusions A prediction formula for MPAP using standard lung function measurements can be used to screen for PH in IPF patients. PMID:18198245

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.

1986-05-22

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patientsmore » with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known.« less

Benefits of pulmonary rehabilitation in idiopathic pulmonary fibrosis.

PubMed

Swigris, Jeffrey J; Fairclough, Diane L; Morrison, Marianne; Make, Barry; Kozora, Elizabeth; Brown, Kevin K; Wamboldt, Frederick S

2011-06-01

Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR's effects on certain important outcomes is lacking. We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. PR improves functional capacity and fatigue in patients with IPF. (Clinical Trials.gov registration NCT00692796.)

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

PubMed Central

Chaisson, Neal F.

2013-01-01

Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease. PMID:24081346

Pulmonary hypertension in older adults.

PubMed

McArdle, John R; Trow, Terence K; Lerz, Kathryn

2007-12-01

Pulmonary hypertension is a frequently encountered problem in older patients. True idiopathic pulmonary arterial hypertension can also be seen and requires careful exclusion in older patients. Institution of therapies must be tempered with an appreciation of individual comorbidities and functional limitations that may affect patients' ability to comply and benefit from the complex treatments available for pulmonary arterial hypertension. This article reviews the existing data on the various forms of pulmonary hypertension presenting in older patients and on appropriate therapy in this challenging population.

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

PubMed

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

PubMed Central

2014-01-01

Background Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Methods Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Results Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). Conclusions This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression

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

PubMed

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.

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.

PubMed

Chilosi, Marco; Caliò, Anna; Rossi, Andrea; Gilioli, Eliana; Pedica, Federica; Montagna, Licia; Pedron, Serena; Confalonieri, Marco; Doglioni, Claudio; Ziesche, Rolf; Grubinger, Markus; Mikulits, Wolfgang; Poletti, Venerino

2017-01-01

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

Benefits of Pulmonary Rehabilitation in Idiopathic Pulmonary Fibrosis

PubMed Central

Swigris, Jeffrey J.; Fairclough, Diane L.; Morrison, Marianne; Make, Barry; Kozora, Elizabeth; Brown, Kevin K.; Wamboldt, Frederick S.

2013-01-01

BACKGROUND Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR’s effects on certain important outcomes is lacking. METHODS We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. RESULTS Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. CONCLUSIONS PR improves functional capacity and fatigue in patients with IPF. (ClinicalTrials.gov registration NCT00692796.) PMID:21333082

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

PubMed

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.

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

King, Talmadge E; Bradford, Williamson Z; Castro-Bernardini, Socorro; Fagan, Elizabeth A; Glaspole, Ian; Glassberg, Marilyn K; Gorina, Eduard; Hopkins, Peter M; Kardatzke, David; Lancaster, Lisa; Lederer, David J; Nathan, Steven D; Pereira, Carlos A; Sahn, Steven A; Sussman, Robert; Swigris, Jeffrey J; Noble, Paul W

2014-05-29

In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P=0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P=0.16) or in rates of death from any cause (P=0.10) or from idiopathic pulmonary fibrosis (P=0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P=0.01) and from idiopathic pulmonary fibrosis (P=0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with

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

PubMed

Caro-Domínguez, Pablo; Compton, Gregory; Humpl, Tilman; Manson, David E

2016-09-01

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

Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis.

PubMed

Brownell, Robert; Kaminski, Naftali; Woodruff, Prescott G; Bradford, Williamson Z; Richeldi, Luca; Martinez, Fernando J; Collard, Harold R

2016-06-01

Precision medicine is defined by the National Institute of Health's Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field's nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management.

Stent-Graft Placement for Femoral Artery Pseudoaneurysm in a Patient with Idiopathic Multiple Arterial Aneurysmal Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koo, Bon Kwon; Choi, Donghoon; Kwon, Kihwan

2002-12-15

A 34-year-old man presenting with a left inguinal mass was diagnosed as having idiopathic multiple aneurysmal disease and pseudoaneurysm of a left superficial femoral artery. A stent-graft was successfully deployed percutaneously at the left superficial femoral artery pseudoaneurysm. Less invasive treatment should be used to avoid vascular complications in patients with idiopathic multiple aneurysmal disease, especially in those who have a progressive course or a history of prior complications after surgical repair.

Pulmonary Arterial Hypertension and Neonatal Arterial Switch Surgery for Correction of Transposition of the Great Arteries.

PubMed

Domínguez Manzano, Paula; Mendoza Soto, Alberto; Román Barba, Violeta; Moreno Galdó, Antonio; Galindo Izquierdo, Alberto

2016-09-01

There are few reports of the appearance of pulmonary arterial hypertension following arterial switch surgery in the neonatal period to correct transposition of the great arteries. We assessed the frequency and clinical pattern of this complication in our series of patients. Our database was reviewed to select patients with transposition of the great arteries corrected by neonatal arterial switch at our hospital and who developed pulmonary hypertension over time. We identified 2 (1.3%) patients with transposition of the great arteries successfully repaired in the first week of life who later experienced pulmonary arterial hypertension. The first patient was a 7-year-old girl diagnosed with severe pulmonary hypertension at age 8 months who did not respond to medical treatment and required lung transplantation. The anatomic pathology findings were consistent with severe pulmonary arterial hypertension. The second patient was a 24-month-old boy diagnosed with severe pulmonary hypertension at age 13 months who did not respond to medical therapy. Pulmonary hypertension is a rare but very severe complication that should be investigated in all patients with transposition of the great arteries who have undergone neonatal arterial switch, in order to start early aggressive therapy for affected patients, given the poor therapeutic response and poor prognosis involved. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of recently validated non-invasive formula using basic lung functions as new screening tool for pulmonary hypertension in idiopathic pulmonary fibrosis patients

PubMed Central

Ghanem, Maha K.; Makhlouf, Hoda A.; Agmy, Gamal R.; Imam, Hisham M. K.; Fouad, Doaa A.

2009-01-01

BACKGROUND: A prediction formula for mean pulmonary artery pressure (MPAP) using standard lung function measurement has been recently validated to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients. OBJECTIVE: To test the usefulness of this formula as a new non invasive screening tool for PH in IPF patients. Also, to study its correlation with patients' clinical data, pulmonary function tests, arterial blood gases (ABGs) and other commonly used screening methods for PH including electrocardiogram (ECG), chest X ray (CXR), trans-thoracic echocardiography (TTE) and computerized tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: Cross-sectional study of 37 IPF patients from tertiary hospital. The accuracy of MPAP estimation was assessed by examining the correlation between the predicted MPAP using the formula and PH diagnosed by other screening tools and patients' clinical signs of PH. RESULTS: There was no statistically significant difference in the prediction of PH using cut off point of 21 or 25 mm Hg (P = 0.24). The formula-predicted MPAP greater than 25 mm Hg strongly correlated in the expected direction with O2 saturation (r = −0.95, P < 0.000), partial arterial O2 tension (r = −0.71, P < 0.000), right ventricular systolic pressure measured by TTE (r = 0.6, P < 0.000) and hilar width on CXR (r = 0.31, P = 0.03). Chest symptoms, ECG and CTPA signs of PH poorly correlated with the same formula (P > 0.05). CONCLUSIONS: The prediction formula for MPAP using standard lung function measurements is a simple non invasive tool that can be used as TTE to screen for PH in IPF patients and select those who need right heart catheterization. PMID:19881164

Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

PubMed

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.

Abnormal Glucose Metabolism and High-Energy Expenditure in Idiopathic Pulmonary Arterial Hypertension

PubMed Central

Malin, Steven K.; Barnes, Jarrod W.; Tian, Liping; Kirwan, John P.; Dweik, Raed A.

2017-01-01

Rationale: Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in patients with IPAH to date. Objectives: To perform comprehensive metabolic phenotyping of humans with IPAH. Methods: We assessed plasma insulin and glucose, using an oral glucose tolerance test and estimated insulin resistance, and β-cell function in 14 patients with IPAH and 14 control subjects matched for age, sex, blood pressure, and body mass index. Body composition (dual-energy X-ray absorptiometry), inflammation (CXC chemokine ligand 10, endothelin-1), physical fitness (6-min walk test), and energy expenditure (indirect calorimetry) were also assessed. Measurements and Main Results: Patients with IPAH had a higher rate of impaired glucose tolerance (57 vs. 14%; P < 0.05) and reduced glucose-stimulated insulin secretion compared with matched control subjects (IPAH: 1.31 ± 0.76 μU/ml⋅mg/dl vs. control subjects: 2.21 ± 1.27 μU/ml⋅mg/dl; P < 0.05). Pancreatic β-cell function was associated with circulating endothelin-1 (r = –0.71, P < 0.01) and CXC chemokine ligand 10 (r = –0.56, P < 0.05). Resting energy expenditure was elevated in IPAH (IPAH: 32 ± 3.4 vs. control subjects: 28.8 ± 2.9 kcal/d/kg fat-free mass; P < 0.05) and correlated with the plasma glucose response (r = 0.51, P < 0.01). Greater insulin resistance was associated with reduced 6-minute walk distance (r = 0.55, P < 0.05). Conclusions: Independent of age, sex, blood pressure, and body mass index, patients with IPAH have glucose intolerance, decreased insulin secretion in response to glucose, and elevated resting energy expenditure. These abnormalities are associated with circulating markers of inflammation and vascular dysfunction. PMID:27922752

Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis

PubMed Central

Brownell, Robert; Kaminski, Naftali; Woodruff, Prescott G.; Bradford, Williamson Z.; Richeldi, Luca; Martinez, Fernando J.

2016-01-01

Precision medicine is defined by the National Institute of Health’s Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field’s nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management. PMID:26991475

Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro-con perspective.

PubMed

Moodley, Yuben; Corte, Tamera; Richeldi, Luca; King, Talmadge E

2015-04-01

Idiopathic pulmonary fibrosis (IPF) is an incurable condition that is characterized by progressive pulmonary fibrosis, architectural distortion of the lung and loss of gas exchange units. Until recently, there was no effective treatment for this condition. However, there were two landmark trials published earlier this year, which have changed the management of this condition. Pirfenidone (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis trial) and nintedanib (Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis-1 and -2 trials) have both demonstrated positive outcomes in patients with IPF. In this perspective, we critically discuss the role of these agents in IPF and in the broader pulmonary fibrosis population. © 2015 Asian Pacific Society of Respirology.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema.

PubMed

Suzuki, Atsushi; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Mori, Yuta; Kondoh, Yasuhiro

2018-01-01

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.

Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography.

PubMed

Wang, Xiaobing; Ren, Weidong; Yang, Jun

2016-04-01

Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS. © 2015, Wiley Periodicals, Inc.

Single origin of right and left pulmonary arteries from ascending aorta with atretic main pulmonary artery from right ventricle and left pulmonary sling.

PubMed

Hsieh, Min-Ling; Huang, Li-Ting; Wang, Jieh-Neng; Tsai, Yi-Shan

2015-01-01

Either left pulmonary sling or single origin of right and left pulmonary arteries (only three cases reported previously) are rare congenital heart anomalies and concomitantly occurred had not been reported. The image presentation is similar to type A1 truncus arteriosus but preserved pulmonary valve and main pulmonary artery development. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

The distribution of immunomodulatory cells in the lungs of patients with idiopathic pulmonary fibrosis

PubMed Central

Nuovo, Gerard J.; Hagood, James S.; Magro, Cynthia M.; Chin, Nena; Kapil, Rubina; Davis, Luke; Marsh, Clay B.; Folcik, Virginia A.

2011-01-01

We have characterized the immune system involvement in the disease processes of idiopathic pulmonary fibrosis in novel ways. To do so, we analyzed lung tissue from 21 cases of idiopathic pulmonary fibrosis and 21 (non-fibrotic, non-cancerous) controls for immune cell and inflammation-related markers. The immunohistochemical analysis of the tissue was grouped by patterns of severity in disease pathology. There were significantly greater numbers of CD68+ and CD80+ cells, and significantly fewer CD3+, CD4+, and CD45RO+ cells in areas of relatively (histologically) normal lung in biopsies from idiopathic pulmonary fibrosis patients compared to controls. In zones of active disease, characterized by epithelial cell regeneration and fibrosis, there were significantly more cells expressing CD4, CD8, CD20, CD68, CD80, CCR6, S100, IL-17, tumor necrosis factor-α, and retinoic acid-related orphan receptors compared to histologically normal lung areas from idiopathic pulmonary fibrosis patients. Inflammation was implicated in these active regions by the cells that expressed retinoid orphan receptor-α, -β, and -γ, CCR6, and IL-17. The regenerating epithelial cells predominantly expressed these pro-inflammatory molecules, as evidenced by co-expression analyses with epithelial cytokeratins. Macrophages in pseudo-alveoli and CD3+ T cells in the fibrotic interstitium also expressed IL-17. Co-expression of IL-17 with retinoid orphan receptors, and epithelial cytoskeletal proteins, CD68, and CD3 in epithelial cells, macrophages, and T-cells, respectively, confirmed the production of IL-17 by these cell types. There was little staining for Foxp3, CD56, or CD34 in any idiopathic pulmonary fibrosis lung regions. The fibrotic regions had fewer immune cells overall. In summary, our study shows participation of innate and adaptive mononuclear cells in active-disease regions of idiopathic pulmonary fibrosis lung, where the regenerating epithelial cells appear to propagate inflammation

Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis.

PubMed

Nathan, Steven D; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Glaspole, Ian; Glassberg, Marilyn K; Kardatzke, David R; Daigl, Monica; Kirchgaessler, Klaus-Uwe; Lancaster, Lisa H; Lederer, David J; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; Noble, Paul W

2017-01-01

In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120. We also did meta-analyses of these data and data from two Japanese trials of pirfenidone versus placebo-Shionogi Phase 2 (SP2) and Shionogi Phase 3 (SP3; trial durations 36-52 weeks). At week 52, the relative risk of death for all four mortality outcomes was significantly lower in the pirfenidone group than in the placebo group in the pooled population (all-cause mortality hazard ratio [HR] 0·52 [95% CI 0·31-0·87; p=0·0107]; treatment-emergent all-cause mortality 0·45 [0·24-0·83; 0·0094]; idiopathic-pulmonary-fibrosis-related mortality 0·35 [0·17-0·72; 0·0029]; treatment-emergent idiopathic-pulmonary-fibrosis-related mortality 0·32 [0·14-0·76; 0·0061]). Consistent with the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed a clinically relevant and significant risk reduction in the pirfenidone group compared with the placebo group. Over 120 weeks, we noted significant differences in the pooled analysis favouring pirfenidone

Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance.

PubMed

Jujo, Takayuki; Sakao, Seiichiro; Ishibashi-Ueda, Hatsue; Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

2015-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation.

Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance

PubMed Central

Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

2015-01-01

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Methods and Results Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. Conclusion The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation. PMID:26252755

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

PubMed

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.

Aggressive Surgical Resection of Pulmonary Artery Intimal Sarcoma.

PubMed

Yamamoto, Yoko; Shintani, Yasushi; Funaki, Soichiro; Taira, Masaki; Ueno, Takayoshi; Kawamura, Tomohiro; Kanzaki, Ryu; Minami, Masato; Sawa, Yoshiki; Okumura, Meinoshin

2018-05-03

Intimal sarcoma of the pulmonary artery is a rare and highly malignant neoplasm. We herein report a case of a 30-year-old woman with an extensive right pulmonary artery tumor who underwent an emergent operation. The tumor was aggressively resected with right pneumonectomy and reconstruction of the right ventricle outflow tract and left pulmonary artery. Although the resected margin at the left pulmonary artery was positive, as confirmed by Mouse double minute type 2 homolog staining, she is doing well and remains free of relapse at 16 months after the operation. Copyright © 2018. Published by Elsevier Inc.

Unusual Systemic Artery to Pulmonary Artery Malformation Without Evidence of Systemic Disease, Trauma or Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geyik, Serdar; Yavuz, Kivilcim; Keller, Frederick S.

2006-10-15

Connections between the systemic and pulmonary arterial systems are rare conditions that can be due to either congenital or acquired diseases such as anomalous systemic arterial supply to normal lung, pulmonary sequestration, and systemic supply to pulmonary arteriovenous malformations. Herein, a unique case of systemic artery to pulmonary arterial malformation and its endovascular treatment in a patient with no history of the usual etiologies is reported.

Pulmonary capillary pressure in pulmonary hypertension.

PubMed

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.

The pulmonary artery catheter: a critical reappraisal.

PubMed

Gidwani, Umesh K; Mohanty, Bibhu; Chatterjee, Kanu

2013-11-01

Balloon floatation pulmonary artery catheters (PACs) have been used for hemodynamic monitoring in cardiac, medical, and surgical intensive care units since the 1970s. With the availability of newer noninvasive diagnostic modalities, particularly echocardiography, the frequency of diagnostic pulmonary artery catheterization has declined. In this review, the evolution of PACs, the results of nonrandomized and randomized studies in various clinical conditions, the uses and abuses of bedside hemodynamic monitoring, and current indications for pulmonary artery catheterization are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulmonary arterial remodeling induced by a Th2 immune response

PubMed Central

Daley, Eleen; Emson, Claire; Guignabert, Christophe; de Waal Malefyt, Rene; Louten, Jennifer; Kurup, Viswanath P.; Hogaboam, Cory; Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.; Rabinovitch, Marlene; Grunig, Ekkehard; Grunig, Gabriele

2008-01-01

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH. PMID:18227220

Pulmonary artery aneurysm and thrombosis in active tuberculous consolidation.

PubMed

Jemshad, A; Ahammed, Shameem; Abdulla, Mansoor C; Musambil, Mohthash

2015-07-01

Tuberculosis continues to remain challenging with a variety of complications. We report the case of a 58-year-old female who developed pulmonary artery aneurysm with intra-arterial thrombus as a complication of active tuberculosis. Even though there are reports of pulmonary artery aneurysm in tuberculous cavity, pulmonary artery aneurysm and intra-arterial thrombus in active tuberculosis are very rare. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Acute and chronic dissection of pulmonary artery: new challenges in pulmonary arterial hypertension?

PubMed

Florczyk, Michał; Wieteska, Maria; Kurzyna, Marcin; Gościniak, Piotr; Pepke-Żaba, Joanna; Biederman, Andrzej; Torbicki, Adam

2018-01-01

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients - high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.

Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

ClinicalTrials.gov

2018-05-16

Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Primary Pulmonary Hypertension; Lung Diseases; Tamoxifen; Estrogen Receptor Antagonist; Hormone Antagonists; Estrogens

[Value of preoperative pulmonary artery diastolic pressure on predicting primary graft dysfunction after bilateral lung transplantation for patients with idiopathic pulmonary fibrosis].

PubMed

Zhang, Feng; Xu, Hongyang; Jiang, Shuyun; Li, Jiaqiong; Lu, Shunmei; Wang, Dapeng; Zang, Zhidong; Pan, Hong; Chen, Jingyu

2017-05-01

To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF). A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation. Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGD group, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non

Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

PubMed

Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

2016-01-01

Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

PubMed

Khatri, Vinod; Neal, Jennifer E; Burger, Charles D; Lee, Augustine S

2015-02-06

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Although multiple SET variables correlated with the RRRS on univariate analyses, only V E /V CO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the V E /V CO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). SETs, particularly the V E /V CO2 , appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Pulmonary arterial hypertension in schistosomiasis.

PubMed

Gavilanes, Francisca; Fernandes, Caio J C; Souza, Rogerio

2016-09-01

Schistosomiasis is one of the most prevalent parasitic diseases in the world, being present in more than 70 countries. Pulmonary hypertension is one of the several chronic complications of schistosomiasis; particularly in developing countries, schistosomiasis-associated pulmonary arterial hypertension might represent one of the most prevalent causes of pulmonary arterial hypertension. New epidemiological data reinforce the importance of schistosomiasis in the context of pulmonary hypertension; furthermore, the inflammatory components of the pathophysiology of pulmonary hypertension associated with schistosomiasis have been recently explored, opening the perspective of new targets to be explored. Clinical and hemodynamic features of this particular complication of schistosomiasis, and the role of targeted therapies in this setting, have been better described in recent years. The importance of schistosomiasis-associated pulmonary hypertension is now recognized with better knowledge about its pathophysiology and management. Nevertheless, there is a need for better understanding the predisposal factors (genetic, environmental and so on) for the development of pulmonary hypertension in schistosomiasis as a way to prevent it from occurring. Furthermore, better control programs to decrease disease transmission are still missing, ensuring that we will have to face this devastating complication of schistosomiasis for a long future.

[Regulation of airway stem cell proliferation in idiopathic pulmonary fibrosis].

PubMed

Yang, S X; Wu, Q; Sun, X; Li, X; Li, K; Xu, L; Li, Y; Zhang, Q Y; Zhang, Y C; Chen, H Y

2016-09-01

To investigate the effect of fibroblasts on regulating airway stem cell proliferation in idiopathic pulmonary fibrosis. Lung cell suspension was prepared from β-actin-GFP mice. Airway stem cells were obtained by fluorescence activated cell sorting and co-cultured with lung fibroblasts. The fibroblasts were treated with TGF-β inhibitor SB43142. The expression of growth factors FGF1/2 and the effect of FGF1/2 on stem cell proliferation were observed. The cloning efficiency of airway stem cells, when co-cultured with normal lung fibroblast cells for 8 days, was (3.5±1.1)%, while the cloning efficiency was reduced to (0.04±0.04)% when co-cultured with lung fibroblasts from idiopathic pulmonary fibrosis patients. The difference between the 2 groups was statistically significant(P=0.002 5). TGF-β receptor inhibitor SB431542 increased lung fibroblast growth factors FGF1/2 expression.FGF1 mRNA expression was increased to the experimental group 0.005 5 from 0.000 2 in the control group.FGF2 mRNA expression of the amount raised to the experimental group 0.000 15 from 0.000 8 in the control group.FGF1/2 promoted the growth of airway stem cells. After FGF1/2 was co-cultured with normal lung fibroblast cells for 8 days, the cloning efficiency of airway stem cells was (0.3±0.1)%. During the development of idiopathic pulmonary fibrosis, fibroblast secreted FGF1/2 regulate airway stem cell proliferation.

Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.

PubMed

Ishimoto, Shinichirou; Sakurai, Hiroyuki; Higure, Ryouta; Kawachi, Riken; Shimamura, Mie

2018-01-15

Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease, and connective tissue disease. Most cases of such aneurysm occur in the trunk or major branches of the pulmonary artery, while the peripheral type is less common. The treatment modalities are medical therapy, surgery, and percutaneous catheter embolization. The mortality rate associated with rupture is approximately 50%. We encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm secondary to pneumonia and cavity formation during chemotherapy for acute myeloid leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT) scan and pulmonary angiography were very useful. He was treated with right middle and lower lobectomy. After 1-month follow-up, he could restart additional chemotherapy.

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected bymore » MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.« less

Anomalous right coronary artery arising from the pulmonary artery and constrictive pericarditis: an unusual association

PubMed Central

Silvestre, Odilson Marcos; Adam, Eduardo Leal; de Melo, Dirceu Thiago Pessoa; Dias, Ricardo Ribeiro; Ramires, Felix J. A.; Mady, Charles

2013-01-01

ABSTRACT The association of anomalous right coronary artery originating from the pulmonary artery and constrictive pericarditis has never been showed in the literature. We present the first case of this unusual association in a patient with right heart failure. After diagnosis, the patient was referred to surgery and underwent phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic artery to right coronary artery; and ligation of the anomalous origin of the right coronary artery from the pulmonary artery. Such procedures solved the potential risk of sudden death related to anomalous right coronary artery originating from the pulmonary artery and alleviated the symptoms of heart failure caused by constrictive pericarditis. PMID:24136766

Echocardiography-based spectrum of severe tricuspid regurgitation: the frequency of apparently idiopathic tricuspid regurgitation.

PubMed

Mutlak, Diab; Lessick, Jonathan; Reisner, Shimon A; Aronson, Doron; Dabbah, Salim; Agmon, Yoram

2007-04-01

The cause of tricuspid valve (TV) regurgitation (TR) occasionally remains unclear. The objectives of our study were to define the causal spectrum of severe TR diagnosed by echocardiography at a tertiary medical center and to assess the relative frequency and determine the clinical and echocardiographic characteristics of TR without an apparent cause (idiopathic TR). Consecutive patients with severe TR were identified by the echocardiography laboratory computerized database. The echocardiographic reports of all patients were reviewed and the causes of TR were determined. The echocardiographic studies and medical charts were reviewed in patients without an obvious cause of TR. Of 242 consecutive patients diagnosed with severe TR, organic TV disease was evident in 23 patients (9.5%) and significant pulmonary hypertension (estimated pulmonary artery systolic pressure > 50 mm Hg) in an additional 157 patients (64.9%). After further excluding patients with various confounding factors, possibly associated with occult organic TV disease or significant pulmonary hypertension, 23 patients (9.5%) had severe TR without an apparent cause. Of these, TV coaptation appeared relatively intact, allowing adequate estimation of pulmonary artery pressure, in 15 patients (6.2% of all patients with severe TR; idiopathic TR group). Patients with idiopathic TR were older (76 +/- 10 years), with a high frequency of atrial fibrillation (93%), and prominent TV annular dilatation. After excluding multiple potential causes of TR, severe TR is occasionally idiopathic. Annular dilatation (secondary to aging, atrial fibrillation, or other causes) is the likely mechanism of TR in these patients.

[Pulmonary arterial hypertension in intensive care unit and operating room].

PubMed

Kerbaul, F; Rondelet, B; Collart, F; Naeije, R; Gouin, F

2005-05-01

To review the perioperative anaesthetic management of pulmonary arterial hypertension. Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

PubMed

Ibrahim, Uroosa; Saqib, Amina; Dhar, Vidhya; Odaimi, Marcel

2018-01-01

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

Gross pulmonary thrombosis in a greyhound.

PubMed

Baines, E A; Watson, P J; Stidworthy, M F; Herrtage, M E

2001-09-01

A two-year-old greyhound was presented with progressive dyspnoea. Radiography showed a hypovascular lung pattern with hyperlucent lung fields and echocardiography revealed a large thrombus in the main pulmonary artery. Blood results showed azotaemia and marked hypoalbuminaemia. The dog's clinical condition continued to deteriorate and it was euthanased. Postmortem examination confirmed the presence of the pulmonary thrombus and revealed idiopathic membranous glomerulonephritis.

Fetal Diagnosis of Abnormal Origin of the Left Pulmonary Artery.

PubMed

Tretter, Justin T; Tretter, Eric M; Rafii, Daniela Y; Anderson, Robert H; Bhatla, Puneet

2016-08-01

Isolated anomalies of the branch pulmonary arteries are rare, more often occurring in the setting of complex congenital heart disease. These isolated anomalies are often not identified in the prenatal period. We describe two cases of isolated anomalies of the left pulmonary artery which were identified on fetal echocardiography and confirmed postnatally, an anomalous left pulmonary artery arising from the base of the left-sided brachiocephalic artery in the setting of a right-sided aortic arch, and a left pulmonary artery sling. These two cases support our current understanding of normal and abnormal development of the extrapericardial arterial vessels and highlight the importance of meticulous attention when sweeping from the three-vessel tracheal view. © 2016, Wiley Periodicals, Inc.

Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

PubMed

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

2000-07-27

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

Mutations of NOTCH3 in childhood pulmonary arterial hypertension

PubMed Central

Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio

2014-01-01

Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512

Acquired pulmonary artery stenosis in four dogs.

PubMed

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

2008-04-15

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

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Utility of electrocardiogram in the assessment and monitoring of pulmonary hypertension (idiopathic or secondary to pulmonary developmental abnormalities) in patients≤18 years of age.

PubMed

Lau, Kelvin C; Frank, David B; Hanna, Brian D; Patel, Akash R

2014-07-15

Electrocardiograms have utility in disease stratification and monitoring in adult pulmonary arterial hypertension (PAH). We examined the electrocardiographic findings that are common in pediatric PAH and assessed for correlation with disease severity and progression. We retrospectively identified patients aged≤18 years followed at a single institution from January 2001 to June 2012 with catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to pulmonary developmental abnormalities. Patients with an electrocardiography performed within 60 days of catheterization were included. Primary and secondary outcomes are the prevalence of abnormal electrocardiographic findings at the time of catheterization and the association between electrocardiographic and hemodynamic findings and electrocardiographic changes with disease progression on follow-up catheterization, respectively. Of the 100 electrocardiography-catheterization pairs derived from the 46 patients identified, 93% had an electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and 52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the presence of RVH and RAD correlated with pulmonary vascular resistance and transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated with an increased risk of disease progression on subsequent catheterization (odds ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH subgroup. The sensitivity, specificity, and positive and negative predictive values of RAD and RVH on baseline electrocardiogram for disease progression were 92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were associated with worse hemodynamics, whereas their absence is suggestive of a lack of disease progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Ten-Year Survival in Patients with Idiopathic Pulmonary Fibrosis After Lung Transplantation.

PubMed

ten Klooster, Liesbeth; Nossent, George D; Kwakkel-van Erp, Johanna M; van Kessel, Diana A; Oudijk, Erik J; van de Graaf, Ed A; Luijk, Bart; Hoek, Rogier A; van den Blink, Bernt; van Hal, Peter Th; Verschuuren, Erik A; van der Bij, Wim; van Moorsel, Coline H; Grutters, Jan C

2015-12-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.

Histopathology of the great vessels in patients with pulmonary arterial hypertension in association with congenital heart disease: large pulmonary arteries matter too.

PubMed

Prapa, Matina; McCarthy, Karen P; Dimopoulos, Konstantinos; Sheppard, Mary N; Krexi, Dimitra; Swan, Lorna; Wort, S John; Gatzoulis, Michael A; Ho, Siew Yen

2013-10-03

Pulmonary arterial hypertension (PAH) is considered primarily a disease of the distal pulmonary arteries whereas little is known on the effect of long-standing pulmonary hypertension on the larger proximal pulmonary arteries. This study aims to investigate the structural changes in the great arteries of adults who developed PAH in association with congenital heart disease (CHD), with severe cases termed Eisenmenger syndrome. We performed macroscopic and light microscopy analyses on the great arteries of 10 formalin-fixed human hearts from patients with PAH/CHD and compared them to age-matched healthy controls. A detailed histology grading score was used to assess the severity of medial wall abnormalities. Severe atherosclerotic lesions were found macroscopically in the elastic pulmonary arteries of 4 PAH/CHD specimens and organised thrombi in 3; none were present in the controls. Significant medial wall abnormalities were present in the pulmonary trunk (PT), including fibrosis (80%), and atypical elastic pattern (80%). Cyst-like formations were present in less than one third of patients and were severe in a single case leading to wall rupture. The cumulative PT histology grading score was significantly higher in PAH/CHD cases compared to controls (p<0.0001) and correlated positively with larger PT diameters (ρ=0.812, p<0.0001) and the degree of medial wall hypertrophy (ρ=0.749, p<0.0001). Chronic PAH in association with CHD results in marked macroscopic and histological abnormalities in the large pulmonary arteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Condliffe, Robin; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

2012-10-01

The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

Variations of pulmonary arteries and other associated defects in Tetralogy of Fallot.

PubMed

Sheikh, Abdul Malik; Kazmi, Uzma; Syed, Najam Hyder

2014-01-01

The objective of study was to determine pulmonary artery variations and other associated cardiac defects in patients with Tetralogy of Fallot. This cross-sectional, descriptive study was carried out at The Children's Hospital and the Institute of Child Health, Lahore, from January 2006 to December 2012. All patients with Tetralogy of Fallot, who underwent cardiac catheterization during this period, were included. Standard cine-angiograms were done to record the pulmonary artery sizes and associated cardiac defects. A total of 576 patients with Tetralogy of Fallot were catheterized. Pulmonary Artery abnormalities were present in 109 (18.92%) patients. The commonest abnormality was isolated Left Pulmonary Artery stenosis (n = 60, 10.4%) followed by supra-valvular stenosis (n = 9, 1.6%). Left Pulmonary Artery was absent in seven patients(1.2%), while 1 patient (0.2%) had both absent right and left Pulmonary Arteries with segmental branch pulmonary arteries originating directly from Main Pulmonary Artery. Associated cardiac lesions included right aortic arch in 72 (12.5%), additional muscular Ventricular Septal Defect in 31 (5.4%), Patent Ductus Arteriosus in 31 (5.4%), bilateral Superior Vena Cava 36(6.2%), Atrial Septal Defect 4(0.7%) and Major Aortopulmonary Collateral Arteries in 75(13%) patients. Significant coronary artery abnormalities were present in 28(4.9%) children. Pulmonary artery abnormalities were present in 18.92% of patients with Tetralogy of Fallot. Isolated Left Pulmonary Artery origin stenosis was the most common abnormality. Significant associated cardiac lesions including Patent Ductus Arteriosus , additional muscular Ventricular Septal Defect, coronary artery abnormalities, bilateral Superior Vena Cava, Atrial Septal Defect and Major Aortopulmonary Collateral Arteries were present in one-third of the patients.

Right ventricular sex differences in patients with idiopathic pulmonary arterial hypertension characterised by magnetic resonance imaging: pair-matched case controlled study.

PubMed

Swift, Andrew J; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-01-01

Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.

Pathogenesis of Idiopathic Pulmonary Fibrosis

PubMed Central

Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

Epigenomics of idiopathic pulmonary fibrosis

PubMed Central

Yang, Ivana V

2012-01-01

Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges and future directions in this field. PMID:22449190

Epigenomics of idiopathic pulmonary fibrosis.

PubMed

Yang, Ivana V

2012-04-01

Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges nd future directions in this field.

A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.

PubMed

Li, Ji-Feng; Zhai, Zhen-Guo; Kuang, Tu-Guang; Liu, Min; Ma, Zhan-Hong; Li, Yi-Dan; Yang, Yuan-Hua

2017-08-01

Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

PubMed

Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

PubMed Central

Mansoor, J. K.; Schelegle, Edward S.; Davis, Cristina E.; Walby, William F.; Zhao, Weixiang; Aksenov, Alexander A.; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

Background An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Methodolgy and Findings Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. Conclusions These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. PMID:24748102

[Patterns, predictors, and personalization in pulmonary arterial hypertension].

PubMed

Kawut, Steven M

2014-06-01

Epidemiologic patterns of pulmonary arterial hypertension differ by era and region and may shed light on the pathophysiology and treatment of the disease. New efforts to target one or more of the recently studied therapies could establish personalized medicine as standard care in pulmonary arterial hypertension.

Magnetic Resonance Imaging in the Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension

PubMed Central

Capener, Dave; Johns, Chris; Hamilton, Neil; Rothman, Alex; Elliot, Charlie; Condliffe, Robin; Charalampopoulos, Athanasios; Rajaram, Smitha; Lawrie, Allan; Campbell, Michael J.; Wild, Jim M.; Kiely, David G.

2017-01-01

Rationale: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). Objectives: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH. Methods: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry. Measurements and Main Results: During the follow-up period of 42 (range, 17–142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P < 0.01): right ventricular end-systolic volume index adjusted for age and sex, and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year (sensitivity, 70 [95% confidence interval (CI), 53–83]; specificity, 62 [95% CI, 62–68]; positive predictive value [PPV], 24 [95% CI, 16–32]; negative predictive value [NPV], 92 [95% CI, 87–96]) and at 3 years (sensitivity, 77 [95% CI, 67–85]; specificity, 73 [95% CI, 66–85]; PPV, 56 [95% CI, 47–65]; and NPV, 87 [95% CI, 81–92]). The model was more accurate in patients with idiopathic PAH at 3 years (sensitivity, 89 [95% CI, 65–84]; specificity, 76 [95% CI, 65–84]; PPV, 60 [95% CI, 46–74]; and NPV, 94 [95% CI, 85–98]). Conclusions: MRI measurements reflecting right ventricular structure and stiffness of the proximal pulmonary vasculature are independent predictors of outcome in PAH. In combination with clinical data MRI has moderate prognostic accuracy in the evaluation of patients with PAH. PMID:28328237

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

PubMed

Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

2018-01-01

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Ultramicronized palmitoylethanolamide (PEA-um(®)) in the treatment of idiopathic pulmonary fibrosis.

PubMed

Di Paola, Rosanna; Impellizzeri, Daniela; Fusco, Roberta; Cordaro, Marika; Siracusa, Rosalba; Crupi, Rosalia; Esposito, Emanuela; Cuzzocrea, Salvatore

2016-09-01

Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um(®)), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis was induced in male mice by a single intratracheal administration of saline with bleomycin sulphate (1mg/kg body weight) in a volume of 100μL. PEA-um(®) was injected intraperitoneally at 1, 3 or 10mg/kg 1h after bleomycin instillation and daily thereafter. Animals were sacrificed after 7 and 21days by pentobarbitone overdose. One cohort of mice was sacrificed after seven days of bleomycin administration, followed by bronchoalveloar lavage and determination of myeloperoxidase activity, lung edema and histopathology features. In the 21-day cohort, mortality was assessed daily, and surviving mice were sacrificed followed by the above analyses together with immunohistochemical localization of CD8, tumor necrosis factor-α, CD4, interleukin-1β, transforming growth factor-β, inducible nitric oxide synthase and basic fibroblast growth factor. Compared to bleomycin-treated mice, animals that received also PEA-um(®) (3 or 10mg/kg) had significantly decreased weight loss, mortality, inflammation, lung damage at the histological level, and lung fibrosis at 7 and 21days. PEA-um(®) (1mg/kg) did not significantly inhibit the inflammation response and lung fibrosis. This study demonstrates that PEA-um(®) (3 and 10mg/kg) reduces the extent of lung inflammation in a mouse model of idiopathic pulmonary fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of pulmonary arterial hypertension associated with congenital heart disease.

PubMed

Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

2007-01-01

Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data.

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis

PubMed Central

Sun, Tong; Liu, Jing; Zhao, De Wei

2016-01-01

Abstract There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis. Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1. Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to −0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02–0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: −0.13–0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: −0.06–0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19–106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3–5.12; P = 0.28) between the N-acetylcysteine group and the control group. N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes

The cancer theory of pulmonary arterial hypertension

PubMed Central

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-based quantitative computed tomography image analysis in idiopathic pulmonary fibrosis: A mini review.

PubMed

Ohkubo, Hirotsugu; Nakagawa, Hiroaki; Niimi, Akio

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive idiopathic interstitial pneumonia in adults. Many computer-based image analysis methods of chest computed tomography (CT) used in patients with IPF include the mean CT value of the whole lungs, density histogram analysis, density mask technique, and texture classification methods. Most of these methods offer good assessment of pulmonary functions, disease progression, and mortality. Each method has merits that can be used in clinical practice. One of the texture classification methods is reported to be superior to visual CT scoring by radiologist for correlation with pulmonary function and prediction of mortality. In this mini review, we summarize the current literature on computer-based CT image analysis of IPF and discuss its limitations and several future directions. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Right ventricular stroke work correlates with outcomes in pediatric pulmonary arterial hypertension.

PubMed

Yang, Weiguang; Marsden, Alison L; Ogawa, Michelle T; Sakarovitch, Charlotte; Hall, Keeley K; Rabinovitch, Marlene; Feinstein, Jeffrey A

2018-01-01

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR). Optimizing treatment strategies and timing for transplant remains challenging. Thus, a quantitative measure to predict disease progression would be greatly beneficial in treatment planning. We devised a novel method to assess right ventricular (RV) stroke work (RVSW) as a potential biomarker of the failing heart that correlates with clinical worsening. Pediatric patients with idiopathic PAH or PAH secondary to congenital heart disease who had serial, temporally matched cardiac catheterization and magnetic resonance imaging (MRI) data were included. RV and PA hemodynamics were numerically determined by using a lumped parameter (circuit analogy) model to create pressure-volume (P-V) loops. The model was tuned using optimization techniques to match MRI and catheterization derived RV volumes and pressures for each time point. RVSW was calculated from the corresponding P-V loop and indexed by ejection fraction and body surface area (RVSW EF ) to compare across patients. Seventeen patients (8 boys; median age = 9.4 years; age range = 4.4-16.3 years) were enrolled. Nine were clinically stable; the others had clinical worsening between the time of their initial matched studies and their most recent follow-up (mean time = 3.9 years; range = 1.1-8.0 years). RVSW EF and the ratio of pulmonary to systemic resistance (Rp:Rs) values were found to have more significant associations with clinical worsening within one, two, and five years following the measurements, when compared with PVR index (PVRI). A receiver operating characteristic analysis showed RVSW EF outperforms PVRI, Rp:Rs and ejection fraction for predicting clinical worsening. RVSW EF correlates with clinical worsening in pediatric PAH, shows promising results towards predicting adverse outcomes, and may serve as an indicator of future clinical worsening.

Transcatheter recanalization of ligated main pulmonary artery.

PubMed

Bhole, Vinay; Wright, John G C; Stumper, Oliver

2007-04-01

A 12.5-year-old boy with tricuspid atresia and quadriplegic cerebral palsy presented with increasing cyanosis after previous palliation with a cavopulmonary shunt and ligation of the main pulmonary artery (MPA). Because of severe physical disabilities he was not considered suitable for Fontan completion. He underwent successful transcatheter stent recanalization of the ligated MPA. This re-established anterograde flow to the pulmonary arteries resulting in marked improvement in saturations.

Angioscopy Is Useful In The Evaluation Of Chronic Pulmonary Arterial Obstruction

NASA Astrophysics Data System (ADS)

Shure, Deborah; Gregoratos, Gabriel; Moser, Kenneth M.

1984-10-01

We have previously described a fiberoptic angioscope for diagnostic use in the right heart and pulmonary arteries. The instrument has a 4 mm 0.D., a proximal flexion control lever, and a 0.8 mm inner channel used to inflate a polyurethane balloon attached to the distal end of the instrument. A conventional xenon light source provides illumination. The instrument is inserted through a right jugular venotomy and passed into the right heart and pulmonary arteries using direct vision and fluoroscopic guidance. The procedure has been performed in 4 patients with pulmonary hypertension suspected to be caused by chronic pulmonary emboli. Chronic emboli were found in two patients and central (resectable) emboli could be distinguished from peripheral ones. The third patient had normal pulmonary arterial intima and a final diagnosis of primary pulmonary hypertension was made. The fourth patient had extrinsic compression of pulmonary arteries by enlarged mediastinal nodes secondary to fibrosing mediastinitis. No complications occurred. We conclude that angioscopy appears to be useful in the diagnostic evaluation of patients with suspected chronic obstruction of the pulmonary arteries.

Rarefaction and blood pressure in systemic and pulmonary arteries

PubMed Central

OLUFSEN, METTE S.; HILL, N. A.; VAUGHAN, GARETH D. A.; SAINSBURY, CHRISTOPHER; JOHNSON, MARTIN

2012-01-01

The effects of vascular rarefaction (the loss of small arteries) on the circulation of blood are studied using a multiscale mathematical model that can predict blood flow and pressure in the systemic and pulmonary arteries. We augmented a model originally developed for the systemic arteries (Olufsen et al. 1998, 1999, 2000, 2004) to (a) predict flow and pressure in the pulmonary arteries, and (b) predict pressure propagation along the small arteries in the vascular beds. The systemic and pulmonary arteries are modelled as separate, bifurcating trees of compliant and tapering vessels. Each tree is divided into two parts representing the `large' and `small' arteries. Blood flow and pressure in the large arteries are predicted using a nonlinear cross-sectional area-averaged model for a Newtonian fluid in an elastic tube with inflow obtained from magnetic resonance measurements. Each terminal vessel within the network of the large arteries is coupled to a vascular bed of small `resistance' arteries, which are modelled as asymmetric structured trees with specified area and asymmetry ratios between the parent and daughter arteries. For the systemic circulation, each structured tree represents a specific vascular bed corresponding to major organs and limbs. For the pulmonary circulation, there are four vascular beds supplied by the interlobar arteries. This manuscript presents the first theoretical calculations of the propagation of the pressure and flow waves along systemic and pulmonary large and small arteries. Results for all networks were in agreement with published observations. Two studies were done with this model. First, we showed how rarefaction can be modelled by pruning the tree of arteries in the microvascular system. This was done by modulating parameters used for designing the structured trees. Results showed that rarefaction leads to increased mean and decreased pulse pressure in the large arteries. Second, we investigated the impact of decreasing vessel

Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

PubMed Central

Menon, Prahlad G; Adhypak, Srilakshmi M; Williams, Ronald B; Doyle, Mark; Biederman, Robert WW

2014-01-01

BACKGROUND We test the hypothesis that cardiac magnetic resonance (CMR) imaging-based indices of four-dimensional (4D) (three dimensions (3D) + time) right ventricle (RV) function have predictive values in ascertaining invasive pulmonary arterial systolic pressure (PASP) measurements from right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH). METHODS We studied five patients with idiopathic PAH and two age and sex-matched controls for RV function using a novel contractility index (CI) for amplitude and phase to peak contraction established from analysis of regional shape variation in the RV endocardium over 20 cardiac phases, segmented from CMR images in multiple orientations. RESULTS The amplitude of RV contractility correlated inversely with RV ejection fraction (RVEF; R2 = 0.64, P = 0.03) and PASP (R2 = 0.71, P = 0.02). Phase of peak RV contractility also correlated inversely to RVEF (R2 = 0.499, P = 0.12) and PASP (R2 = 0.66, P = 0.04). CONCLUSIONS RV contractility analyzed from CMR offers promising non-invasive metrics for classification of PAH, which are congruent with invasive pressure measurements. PMID:25624777

Computed tomographic features of idiopathic fibrosing interstitial pneumonia: comparison with pulmonary fibrosis related to collagen vascular disease.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Sahin, Hakan; Brown, Kevin K; Newell, John D; Lynch, David A

2009-01-01

To compare the computed tomographic (CT) features of idiopathic fibrosing interstitial pneumonia with those of pulmonary fibrosis related to collagen vascular disease (CVD). We reviewed the CT scans of 177 patients with diffuse interstitial pulmonary fibrosis, of which 97 had idiopathic fibrosing interstitial pneumonia and 80 had CVD. The CT images were systematically scored for the presence and extent of pulmonary and extrapulmonary abnormalities. Computed tomographic diagnosis of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was assigned. A CT pattern of UIP was identified in 59 (60.8%) of patients with idiopathic fibrosing interstitial pneumonia compared with 15 (18.7%) of those patients with CVD; conversely, the CT diagnosis of NSIP was made in 51 (64%) of patients with CVD compared with 36 (37%) of patients with idiopathic disease (P < 0.01). In 113 patients who had lung biopsy, the CT diagnoses of UIP and NSIP were concordant with the histologic diagnoses in 36 of 50 patients and 34 of 41 patients, respectively. Pleural effusions, esophageal dilation, and pericardial abnormalities were more frequent in patients with CVD than in patients with idiopathic fibrosing interstitial pneumonia. Compared with patients with CVD, those patients with an idiopathic fibrosing interstitial pneumonia showed a higher prevalence of a UIP pattern and lower prevalence of an NSIP pattern as determined by CT. Identification of coexisting extrapulmonary abnormalities on CT can support a diagnosis of CVD.

Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Su, Junjing; Manisty, Charlotte; Parker, Kim H; Simonsen, Ulf; Nielsen-Kudsk, Jens Erik; Mellemkjaer, Soren; Connolly, Susan; Lim, P Boon; Whinnett, Zachary I; Malik, Iqbal S; Watson, Geoffrey; Davies, Justin E; Gibbs, Simon; Hughes, Alun D; Howard, Luke

2017-10-31

In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

IDIOPATHIC PULMONARY FIBROSIS: NEW CONCEPTS IN PATHOGENESIS AND IMPLICATIONS FOR DRUG THERAPY

PubMed Central

Horowitz, Jeffrey C.; Thannickal, Victor J.

2008-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal pulmonary disease for which there are no proven or approved drug therapies. Anti-inflammatory and immunosuppressive agents have been largely ineffective. The precise relationship of IPF to other idiopathic interstitial pneumonias (IIPs) is not known, despite the observation that different histopathological patterns of IIP may co-exist in the same patient. We propose that these different histopathological “reaction” patterns may be determined by complex interactions between host and environmental factors that alter the local alveolar milieu. Recent paradigms in IPF pathogenesis have focused on dysregulated epithelial-mesenchymal interactions, an imbalance in TH1/TH2 cytokines and potential roles for aberrant angiogenesis. In this review, we discuss these evolving concepts in disease pathogenesis and emerging therapies designed to target pro-fibrogenic pathways in IPF. PMID:16928146

Nonmassive acute pulmonary embolism: evaluation of the impact of pulmonary arterial wall distensibility on the assessment of the CT obstruction score.

PubMed

Bigot, Julien; Rémy-Jardin, Martine; Duhamel, Alain; Gorgos, Andréi-Bogdan; Faivre, Jean-Baptiste; Rémy, Jacques

2010-02-01

To evaluate the impact of pulmonary arterial wall distensibility on the assessment of a computed tomography (CT) score in patients with nonmassive pulmonary embolism (PE) (ie, Mastora score). The arterial wall distensibility of five central pulmonary arteries (pulmonary artery trunk, right and left main pulmonary arteries, right and left interlobar pulmonary arteries) was studied on ECG-gated CT angiographic studies of the chest in 15 patients with no pulmonary arterial hypertension (group 1; mean pulmonary artery pressure: 17.2 mm Hg) and 9 patients with nonmassive PE (group 2), using 2D reconstructions at every 10% of the R-R interval. The systolic and diastolic reconstruction time windows of the examined arteries were identical in the 2 groups, obtained at 20% and 80% of the R-R interval, respectively. No statistically significant difference was observed between the mean values of the pulmonary arterial wall distensibility between the 2 groups, varying between 20.5% and 24% in group 1 and between 23.3% and 25.9% in group 2. The coefficients of variation of the average arterial surfaces were found to vary between 4.30% and 6.50% in group 1 and 4.2% and 8.4% in group 2. Except the pulmonary artery trunk in group 2, all the intraclass correlation coefficients were around 0.8 or greater than 0.8, that is the cutoff for good homogeneity of measurements. The pulmonary arterial wall systolic-diastolic distensibility does not interfere with the assessment of a CT obstruction score in the setting of nonmassive PE.

GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

PubMed Central

2011-01-01

Background Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH). Methods GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein. Results GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein. Conclusions GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients. PMID:21548946

Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.

PubMed

Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu; Tamosiuniene, Rasa; Wang, Lingli; Sharpe, Orr; Samayoa, Erik; Harada, Daisuke; Moonen, Jan-Renier A J; Cao, Aiqin; Chen, Pin-I; Hennigs, Jan K; Gu, Mingxia; Li, Caiyun G; Leib, Ryan D; Li, Dan; Adams, Christopher M; Del Rosario, Patricia A; Bill, Matthew; Haddad, Francois; Montoya, Jose G; Robinson, William H; Fantl, Wendy J; Nolan, Garry P; Zamanian, Roham T; Nicolls, Mark R; Chiu, Charles Y; Ariza, Maria E; Rabinovitch, Marlene

2017-11-14

Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies. Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat. SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor

Non-valvular main pulmonary artery vegetation associated with aortopulmonary window.

PubMed

Unal, M; Tuncer, C; Serçe, K; Bostan, M; Gökçe, M; Erem, C

1995-01-01

We present a 32-year-old female with aortopulmonary window and vegetation of non-valvular main pulmonary artery. The aortopulmonary window is a rare congenital disease in which the aorta and pulmonary arteries are communicated by a defect of variable diameter. The pulmonic valve is the least commonly involved valve in bacterial endocarditis, but there is no vegetation of non-valvular main pulmonary artery in the literature. Colour duplex sonography showed an aortopulmonary window with aortic regurgitation. Magnetic resonance (MR) imaging demonstrating the vegetation on the wall of main pulmonary artery, is an useful and complementary method, and can be used for demonstration of congenital and acquired cardiovascular pathologies including aortopulmonary window and subpulmonic or suprapulmonic vegetations.

Time for a change: is idiopathic pulmonary fibrosis still idiopathic and only fibrotic?

PubMed Central

Wolters, Paul J; Blackwell, Timothy S; Eickelberg, Oliver; Loyd, James E; Kaminski, Naftali; Jenkins, Gisli; Maher, Toby M; Molina-Molina, Maria; Noble, Paul W; Raghu, Ganesh; Richeldi, Luca; Schwarz, Marvin I; Selman, Moises; Wuyts, Wim A; Schwartz, David A

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and typically fatal lung disease characterised by subpleural fibrosis, subepithelial fibroblast foci, and microscopic honeycombing. Although understanding of the pathogenic mechanisms continues to evolve, evidence indicates that distal airway and alveolar epithelial cells are central drivers of the disease. In this Viewpoint, we review the history of naming and classifications used to define the disease now referred to as IPF, in the context of understanding the clinical presentation, causes, and pathogenesis of the disease. We aim to generate discussion on whether, given the substantial progress made in understanding the clinical, genetic, cellular, and molecular mechanisms involved in the development of IPF, a change of name should be considered. To initiate this discussion, we offer new suggestions to update the name of this disease and new approaches to classify all forms of pulmonary fibrosis. PMID:29413083

Further characterization of computed tomographic and clinical features for staging and prognosis of idiopathic pulmonary fibrosis in West Highland white terriers.

PubMed

Thierry, Florence; Handel, Ian; Hammond, Gawain; King, Lesley G; Corcoran, Brendan M; Schwarz, Tobias

2017-07-01

Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (ρ = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (ρ = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P < 0.001). The most common CT characteristics were ground-glass pattern (16/21) considered as a mild degree of severity, and focal reticular and mosaic ground-glass patterns (10/21) considered as a moderate degree of severity. Findings supported the use of thoracic CT as a method for characterizing idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. © 2017 The Authors

Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

PubMed Central

Frank, Benjamin S.

2018-01-01

Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed. PMID:29570688

Anomalous left coronary artery from the pulmonary artery

MedlinePlus

... begins from the pulmonary artery instead of the aorta. ALCAPA is present at birth (congenital) . Causes ALCAPA ... the normal heart, the LCA originates from the aorta. It supplies oxygen-rich blood to the heart ...

Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

PubMed

Cottin, Vincent; Hansell, David M; Sverzellati, Nicola; Weycker, Derek; Antoniou, Katerina M; Atwood, Mark; Oster, Gerry; Kirchgaessler, Klaus-Uwe; Collard, Harold R; Wells, Athol U

2017-11-01

Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV 1 /FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

GPCRs in pulmonary arterial hypertension: tipping the balance.

PubMed

Iyinikkel, Jean; Murray, Fiona

2018-02-21

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease characterised by increased pulmonary vascular resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMC). GPCRs, which are attractive pharmacological targets, are important regulators of pulmonary vascular tone and PASMC phenotype. PAH is associated with the altered expression and function of a number of GPCRs in the pulmonary circulation, which leads to the vasoconstriction and proliferation of PASMC and thereby contributes to the imbalance of pulmonary vascular tone associated with PAH; drugs targeting GPCRs are currently used clinically to treat PAH and extensive preclinical work supports the utility of a number of additional GPCRs. Here we review how GPCR expression and function changes with PAH and discuss why GPCRs continue to be relevant drug targets for the disease. © 2018 The British Pharmacological Society.

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

PubMed

Kazimierczyk, Remigiusz; Kamiński, Karol

2018-06-06

Pulmonary arterial hypertension is a multifactorial disease characterized by vasoconstriction, vascular remodeling, inflammation and thrombosis. Although an increasing number of research confirmed that pulmonary artery endothelial cells, pulmonary artery smooth muscle cells as well as platelets have a role in the pulmonary arterial hypertension pathogenesis, it is still unclear what integrates these factors. In this paper, we review the evidence that platelets through releasing a large variety of chemokines could actively impact the pulmonary arterial hypertension pathogenesis and development. A recent publication revealed that not only an excess of platelet derived cytokines, but also a deficiency may be associated with pulmonary arterial hypertension development and progression. Hence, a simple platelet blockade may not be a correct action to treat pulmonary arterial hypertension. Our review aims to analyse the interactions between the platelets and different types of cells involved in pulmonary arterial hypertension pathogenesis. This knowledge could help to find novel therapeutic options and improve prognosis in this devastating disease. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Right Ventricular Structure and Function in Idiopathic Pulmonary Fibrosis with or without Pulmonary Hypertension.

PubMed

D'Andrea, Antonello; Stanziola, Anna; Di Palma, Enza; Martino, Maria; D'Alto, Michele; Dellegrottaglie, Santo; Cocchia, Rosangela; Riegler, Lucia; Betancourt Cordido, Meredyth Vanessa; Lanza, Maurizia; Maglione, Marco; Diana, Veronica; Calabrò, Raffaele; Russo, Maria Giovanna; Vannan, Mani; Bossone, Eduardo

2016-01-01

To elucidate right ventricular (RV) function in patients with idiopathic pulmonary fibrosis (IPF) with and without pulmonary hypertension (PH) and its relation to other features of the disease. Clinical evaluation, standard Doppler echo, Doppler myocardial imaging (DMI), and 2D strain echocardiography (STE) of RV septal and lateral walls were performed in 52 IPF patients (66.5 ± 8.5 years; 27 males) and in 45 age- and sex-comparable controls using a commercial US system (MyLab Alpha, Esaote). Pulmonary artery mean pressure (mPAP) was estimated by standard echo Doppler. RV global longitudinal strain (RV GLS) was calculated by averaging RV local strains. The IPF patients were divided into 2 groups by noninvasive assessment of PH: no PH (mPAP<25 mmHg; 36 pts) and PH (mPAP ≥25 mmHg; 16 pts). Left ventricular diameters and ejection fraction were comparable between controls and IPF, while GLS was impaired in IPF (P < 0.01). RV end-diastolic diameters, wall thickness andmPAP were increased in IPF patients with PH. In addition, pulsed DMI detected in PH IPF impaired myocardial RV early diastolic (Em) peak velocity. Also peak systolic RV strain was reduced in basal and middle RV lateral free walls in IPF, as well as RV GLS (P < 0.0001). The impairment in RV wall strain was more evident when comparing controls with the no PH group than comparing the no PH group with the PH group. By multivariate analysis, independent association of RV strain with both six-minute walking test distance (P < 0.001), mPAP (P < 0.0001), as well as with forced vital capacity (FVC) % (P < 0.005) in IPF patients were observed. Impaired RV diastolic and systolic myocardial function were present even in IPF patients without PH, which indicates an early impact on RV function and structure in patients with IPF. © 2015, Wiley Periodicals, Inc.

EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension.

PubMed

Best, D Hunter; Sumner, Kelli L; Smith, Benjamin P; Damjanovich-Colmenares, Kristy; Nakayama, Ikue; Brown, Lynette M; Ha, Youna; Paul, Eleri; Morris, Ashley; Jama, Mohamed A; Dodson, Mark W; Bayrak-Toydemir, Pinar; Elliott, C Gregory

2017-04-01

Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH. Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations. Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.

PubMed

Han, MeiLan K; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Noth, Imre; Lama, Vibha N; Moore, Bethany B; White, Eric S; Flaherty, Kevin R; Huffnagle, Gary B; Martinez, Fernando J

2014-07-01

The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis. Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a p<0.10. These OTUs were then used in the analysis of the principal components. The association between principal components and microbes with high factor loadings and progression-free survival were assessed with Cox regression analyses. The COMET study is registered with ClinicalTrials.gov, number NCT01071707. Mean FVC was 70.1% (SD 17.0) and DLCO 42.3% (14.0) of predicted. Disease progression was significantly associated with increased relative abundance of two OTUs-Streptococcus OTU 1345 (relative risk 1.11, 95% CI 1.04-1.18; p=0.0009) and Staphylococcus OTU 1348 (1.16, 1.03-1.31, p=0.012). Thresholds for relative abundance of each OTU associated with progression-free survival were more than 3.9% for Streptococcus OTU 1345 (10.19, 2.94-35.35; p=0.0002) and more than 1.8% for Staphylococcus OTU 1348 (5.06, 1.71-14.93; p=0.003). These preliminary data suggest progression of idiopathic pulmonary fibrosis is associated with the presence of specific members within the

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

PubMed

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

2018-05-29

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

IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

EPA Science Inventory

Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

Resolution of Behçet's syndrome associated pulmonary arterial aneurysms with infliximab.

PubMed

Schreiber, Benjamin E; Noor, Nadim; Juli, Christoph F; Haskard, Dorian O

2011-12-01

We describe the successful treatment of pulmonary arterial aneurysms in Behçet's syndrome using a tumor necrosis factor (TNF) inhibitor. A case is reported of Behçet's syndrome complicated by pulmonary arterial aneurysms that responded to anti-TNF therapy. This is accompanied by a literature review of previously published cases. We searched the English language medical literature using the PubMed and Medline search terms: "Behçet's," "Pulmonary aneurysms," and "infliximab," "etanercept," or "adalimumab." A 43-year-old man with a 6-month history of oral and genital ulcers, weight loss, and fatigue developed arterial aneurysms in the common carotid and common iliac arteries and thromboses in a femoral vein and pulmonary arteries. Treatment with high-dose oral corticosteroids and pulsed intravenous cyclophosphamide was initiated but while on treatment he developed pulmonary arterial aneurysms with hemoptysis. His treatment was changed to intravenous infliximab with methotrexate to which he showed a good response with marked clinical improvement, reduction in his inflammatory markers, and regression of the pulmonary arterial aneurysms. The review of the literature identified 3 reported cases of treatment of pulmonary arterial aneurysms in Behçet's syndrome with anti-TNF therapy, with good outcomes in each case. Pulmonary artery aneurysms are important complications of Behçet's syndrome. Anti-TNF inhibitors should be considered in patients who do not respond to treatment with corticosteroids and cyclophosphamide. Copyright © 2011 Elsevier Inc. All rights reserved.

Prenatal diagnosis of left pulmonary artery-to-pulmonary vein fistula and its successful surgical repair in a neonate.

PubMed

Ostras, Oleksii; Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

2015-04-01

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair.

Recent advances in managing idiopathic pulmonary fibrosis

PubMed Central

Scelfo, Chiara; Caminati, Antonella; Harari, Sergio

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a rare pulmonary disease with a poor prognosis and severe impact on quality of life. Early diagnosis is still challenging and important delays are registered before final diagnosis can be reached. Available tools fail to predict the variable course of the disease and to evaluate response to antifibrotic drugs. Despite the recent approval of pirfenidone and nintedanib, significant challenges remain to improve prognosis and quality of life. It is hoped that the new insights gained in pathobiology in the last few years will lead to further advances in the diagnosis and management of IPF. Currently, early diagnosis and prompt initiation of treatments reducing lung function loss offer the best hope for improved outcomes. This article aims at providing an overview of recent advances in managing patients with IPF and has a particular focus on how to reach a diagnosis, manage comorbidities and lung transplantation, care for the non-pharmacological needs of patients, and address palliative care. PMID:29225786

Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD

PubMed Central

Sims, Michael W.; Margolis, David J.; Localio, A. Russell; Panettieri, Reynold A.; Kawut, Steven M.; Christie, Jason D.

2009-01-01

Background: Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined. Methods: We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed. Results: The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04). Conclusions: Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown. PMID:19318664

Right Ventricular Sex Differences in Patients with Idiopathic Pulmonary Arterial Hypertension Characterised by Magnetic Resonance Imaging: Pair-Matched Case Controlled Study

PubMed Central

Swift, Andrew J.; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M.; Elliot, Charlie; Condliffe, Robin; Wild, Jim M.; Kiely, David G.

2015-01-01

Purpose Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females. PMID:25996939

Bilateral multiple pulmonary artery aneurysms associated with cavitary pulmonary tuberculosis: a case report.

PubMed

Pallangyo, Pedro; Lyimo, Frederick; Bhalia, Smita; Makungu, Hilda; Nyangasa, Bashir; Lwakatare, Flora; Suranyi, Pal; Janabi, Mohamed

2017-07-19

Pulmonary artery aneurysms constitute <1% of aneurysms occurring in the thoracic cavity. Congenital cardiac defects are responsible for the majority (>50%) of cases, however, pulmonary artery aneurysm is a rare sequelae of pulmonary tuberculosis reported in about 5% of patients with chronic cavitary tuberculosis on autopsy. The natural history of this potentially fatal condition remains poorly understood and guidelines for optimal management are controversial. A 24-year-old man, a nursing student of African descent, was referred to us from an up-country regional hospital with a 4-week history of recurrent episodes of breathlessness, awareness of heartbeats and coughing blood 3 weeks after completing a 6-month course of anti-tuberculosis drugs. A physical examination revealed conjuctival and palmar pallor but there were no stigmata of connective tissue disorders, systemic vasculitides or congenital heart disease. An examination of the cardiovascular system revealed accentuated second heart sound (S 2 ) with early diastolic (grade 1/6) and holosystolic (grade 2/6) murmurs at the pulmonic and tricuspid areas respectively. Blood tests showed iron deficiency anemia, prolonged bleeding time, and mild hyponatremia. A chest radiograph revealed bilateral ovoid-shaped perihilar opacities while a computed tomography scan showed bilateral multiple pulmonary artery pseudoaneurysms with surrounding hematoma together with adjacent cystic changes, consolidations, and tree-in-bud appearance. Our patient refused to undergo surgery and died of aneurismal rupture after 9 days of hospitalization. The presence of intractable hemoptysis among patients with tuberculosis even after completion of anti-tuberculosis course should raise an index of suspicion for pulmonary artery aneurysm. Furthermore, despite of its rarity, early recognition and timely surgical intervention of pulmonary artery aneurysm is crucial to reducing morbidity and preventing the attributed mortality.

Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease.

PubMed

Galiè, Nazzareno; Denton, Christopher P; Dardi, Fabio; Manes, Alessandra; Mazzanti, Gaia; Li, Baohui; Varanese, Lucio; Esler, Anne; Harmon, Cathi; Palazzini, Massimiliano

2017-05-15

The primary objective of this post hoc analysis was to evaluate clinical outcomes of tadalafil in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD-PAH) compared with patients with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy endpoints, and safety. This analysis included adult patients with CTD-PAH or I/H-PAH who participated in the PHIRST and PHIRST-2 studies. Patients were randomized 1:1:1:1:1 to tadalafil (2.5, 10, 20, or 40mg) or placebo in the PHIRST study and the majority of these patients were subsequently assigned 40mg in PHIRST-2. Patients taking 20mg in PHIRST without demonstrating clinical worsening continued on 20mg in PHIRST-2. Outcomes analyzed included 6MWD, WHO-FC, and incidence and time to first occurrence of clinical worsening. Safety was assessed through evaluation of adverse events (AEs), clinical laboratory data, electrocardiograms, and physical examinations. Increased 6MWD in PHIRST was maintained in both CTD-PAH and I/H-PAH subgroups for 52weeks. Patients with CTD-PAH tended to be older, were more likely female, had lower exercise capacity, were more likely to have clinical worsening, and experienced AEs more frequently than patients with I/H-PAH. The effect of tadalafil treatment in patients enrolled in both PHIRST studies was detectable for both I/H-PAH and CTD-PAH subgroups. In general, subgroup differences were modest. Patients with CTD-PAH may perform less well than patients with I/H-PAH in safety and efficacy measures in all treatment groups, which is similar to other studies demonstrating a worse prognosis for patients with CTD-PAH. Copyright © 2017. Published by Elsevier B.V.

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

PubMed

Khalil, Nasreen; O'Connor, Robert

2004-07-20

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

[Definition and classification of pulmonary arterial hypertension].

PubMed

Nakanishi, Norifumi

2008-11-01

Pulmonary hypertension(PH) is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary vasculature. Because an accurate diagnosis of PH in a patient is essential to establish an effective treatment, a classification of PH has been helpful. The first classification, established at WHO Symposium in 1973, classified PH into groups based on the known cause and defined primary pulmonary hypertension (PPH) as a separate entity of unknown cause. In 1998, the second World Symposium on PPH was held in Evian. Evian classification introduced the concept of conditions that directly affected the pulmonary vasculature (i.e., PAH), which included PPH. In 2003, the third World Symposium on PAH convened in Venice. In Venice classification, the term 'PPH' was abandoned in favor of 'idiopathic' within the group of disease known as 'PAH'.

Prenatal Diagnosis of Left Pulmonary Artery-to-Pulmonary Vein Fistula and Its Successful Surgical Repair in a Neonate

PubMed Central

Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

2015-01-01

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair. PMID:25873833

Partial anomalous left pulmonary artery: report of two cases and review of literature.

PubMed

Sen, Supratim; Winlaw, David S; Sholler, Gary F

2015-06-01

We describe two cases of anomalous origin of the left lower-lobe pulmonary artery from the right pulmonary artery. The primary diagnosis was mitral atresia, hypoplastic left ventricle, aortic arch hypoplasia in the first child, and tetralogy of Fallot in the second. In both cases, the pulmonary trunk gave rise to a left pulmonary artery in the normal position. In addition, a second branch of the left pulmonary artery arose from the right pulmonary artery, and passed posterior and inferior to the left main or upper-lobe bronchus to supply the left lower lobe. In this review, we compare our findings with previously reported examples of this extremely rare cardiac malformation, and discuss possible embryological explanations for the lesion.

Pulmonary Hypertension in Parenchymal Lung Disease

PubMed Central

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

PubMed

Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

1999-04-01

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

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

PubMed

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.

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report.

PubMed

Grech, Victor; Grixti, Cynthia

2010-06-02

Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation.

Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

PubMed

Dykes, John C; Torres, Marilyn; Alexander, Plato J

2016-03-01

This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

PubMed Central

Putman, Rachel K.; Rosas, Ivan O.

2014-01-01

Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. PMID:24547893

Management of pulmonary arterial hypertension.

PubMed

McLaughlin, Vallerie V; Shah, Sanjiv J; Souza, Rogerio; Humbert, Marc

2015-05-12

Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

PubMed Central

Sarrion, Irene; Milian, Lara; Juan, G.; Ramon, Mercedes; Furest, Idelfonso; Carda, Carmen; Cortijo Gimeno, Julio; Mata Roig, Manuel

2015-01-01

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients' pulmonary function. We also studied the expression profile of circulating messenger RNA (mRNAs) and found that miR23a controlled 17% of the significantly changed mRNA, including PGC1α, which was recently associated with the progression of IPAH. Finally we found that silencing of miR23a resulted in an increase of the expression of PGC1α, as well as in its well-known regulated genes CYC, SOD, NRF2, and HO1. The results point to the utility of circulating miRNA expression as a biomarker of disease progression. PMID:25815108

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report

PubMed Central

2010-01-01

Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186

Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

PubMed Central

Nakamura, Yutaro; Suda, Takafumi

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension.

PubMed

Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok

2015-10-01

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

Pulmonary arterial hypertension: Specialists’ knowledge, practices, and attitudes of genetic counseling and genetic testing in the USA

PubMed Central

Jacher, Joseph E.; Martin, Lisa J.; Chung, Wendy K.; Loyd, James E.; Nichols, William C.

2017-01-01

Pulmonary arterial hypertension (PAH) is characterized by obstruction of pre-capillary pulmonary arteries, which leads to sustained elevation of pulmonary arterial pressure. Identifying those at risk through early interventions, such as genetic testing, may mitigate disease course. Current practice guidelines recommend genetic counseling and offering genetic testing to individuals with heritable PAH, idiopathic PAH, and their family members. However, it is unclear if PAH specialists follow these recommendations. Thus, our research objective was to determine PAH specialists’ knowledge, utilization, and perceptions about genetic counseling and genetic testing. A survey was designed and distributed to PAH specialists who primarily work in the USA to assess their knowledge, practices, and attitudes about the genetics of PAH. Participants’ responses were analyzed using parametric and non-parametric statistics and groups were compared using the Wilcoxon rank sum test. PAH specialists had low perceived and actual knowledge of the genetics of PAH, with 13.2% perceiving themselves as knowledgeable and 27% actually being knowledgeable. Although these specialists had positive or ambivalent attitudes about genetic testing and genetic counseling, they had poor utilization of these genetic services, with almost 80% of participants never or rarely ordering genetic testing or referring their patients with PAH for genetic counseling. Physicians were more knowledgeable, but had lower perceptions of the value of genetic testing and genetic counseling compared to non-physicians (P < 0.05). The results suggest that increased education and awareness is needed about the genetics of PAH as well as the benefits of genetic testing and genetic counseling for individuals who treat patients with PAH. PMID:28597770

Mid-term outcomes of patients undergoing adjustable pulmonary artery banding

PubMed Central

Talwar, Sachin; Kamat, Neeraj Aravind; Choudhary, Shiv Kumar; Ramakrishnan, Sivasubramanian; Saxena, Anita; Juneja, Rajnish; Kothari, Shyam Sunder; Airan, Balram

2016-01-01

Objective The adjustable pulmonary artery band (APAB) has been demonstrated by us earlier to be superior to the conventional pulmonary artery banding (CPAB), in terms of reduced early morbidity and mortality. In this study, we assessed the adequacy of the band and its complications over the mid-term. Methods Between 2002 and 2012, 73 patients underwent adjustable PAB, and their operative and follow-up data were collected and analyzed. Results There was one early death following the APAB. Follow-up data were available for 57 patients of which 44 patients (61.7%) underwent definitive repair, 10 were awaiting definitive repair, and 3 patients were kept on medical follow-up because of inadequate fall in pulmonary artery (PA) pressures. 14 patients (19%) were lost to follow-up. Major PA distortion or stenosis was absent in the majority. 1 patient had pseudoaneurysm of the main pulmonary artery (MPA) with sternal sinus infection and required surgical reconstruction. 1 patient had infective endocarditis of the pulmonary valve managed medically. Band migration was not encountered. There were two deaths after definitive repair and one after APAB. Conclusions Patients undergoing APAB fulfilled the desired objectives of the pulmonary artery banding (PAB) with minimum PA complications in the mid-term. This added to the early postoperative benefits, makes the APAB an attractive alternative to the CPAB. PMID:26896271

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

PubMed

Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

2014-01-01

To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

Dynamic patient counseling: a novel concept in idiopathic pulmonary fibrosis.

PubMed

Brown, A Whitney; Shlobin, Oksana A; Weir, Nargues; Albano, Maria C; Ahmad, Shahzad; Smith, Mary; Leslie, Kevin; Nathan, Steven D

2012-10-01

The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation. Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter. Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival.

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

PubMed

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 artery dissection in eight dogs with patent ductus arteriosus.

PubMed

Scansen, Brian A; Simpson, Elaine M; López-Alvarez, Jordi; Thomas, William P; Bright, Janice M; Eason, Bryan D; Rush, John E; Dukes-McEwan, Joanna; Green, Henry W; Cunningham, Suzanne M; Visser, Lance C; Kent, Agnieszka M; Schober, Karsten E

2015-06-01

To describe a series of dogs with pulmonary artery dissection and patent ductus arteriosus (PDA). Eight dogs. Retrospective case series. Pulmonary artery dissection was diagnosed in 8 dogs, 3 were Weimaraners. Four dogs presented in left-sided congestive heart failure, 4 presented for murmur evaluation and without clinical signs, and 1 presented in right-sided congestive heart failure. In 7 dogs the dissection was first documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with pulmonary valve stenosis and PDA, the dissection was observed on autopsy examination 17 months after balloon pulmonary valvuloplasty and ductal closure. Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog underwent successful transcatheter device occlusion of the PDA, and 1 dog had the PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1 and 3 years after diagnosis due to heart failure. Pulmonary artery dissection is a potential complication of PDA in dogs, the Weimaraner breed may be at increased risk, presentation is often in mature dogs, and closure of the PDA can be performed and appears to improve outcome. Copyright © 2014 Elsevier B.V. All rights reserved.

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

PubMed

Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Translation to Spanish and Validation of the Specific Saint George's Questionnaire for Idiopathic Pulmonary Fibrosis.

PubMed

Capparelli, Ignacio; Fernandez, Martín; Saadia Otero, Marcela; Steimberg, Jimena; Brassesco, María; Campobasso, Ana; Palacios, Sandra; Caro, Fabian; Alberti, María Laura; Rabinovich, Roberto A; Paulin, Francisco

2018-02-01

Interstitial lung disease (ILD) is associated with low exercise tolerance, dyspnea, and decreased health-related quality of life (HRQL). Idiopathic pulmonary fibrosis (IPF) is one of the most prevalent in the group. A specific version of the Saint George's questionnaire (SGRQ-I) has been developed to quantify the HRQL of IPF patients. However, this tool is not currently validated in the Spanish language. The objective was to translate into Spanish and validate the specific Saint George's Respiratory Questionnaire for idiopathic pulmonary fibrosis (SGRQ-I). The repeatability, internal consistency and construct validity of the SGRQ-I in Spanish were analyzed after a backtranslation process. In total, 23 outpatients with IPF completed the translated SGRQ-I twice, 7 days apart. Repeatability was studied, revealing good concordance in test-retest with an ICC (interclass correlation coefficient) of 0.96 (P<.001). Internal consistency was good for different questionnaire items (Cronbach's alpha of 0.9 including and 0.81 excluding the total value) (P<.001). The total score of the questionnaire showed good correlation with forced vital capacity FVC% (r=-0.44; P=.033), diffusing capacity of the lungs for carbon monoxide (DL CO %) (r=-0.55; P=.011), partial pressure of oxygen in arterial blood PaO 2 (r=-0.44; P=.036), Medical Research Council Dyspnea scale (r=-0.65; P<.001), and number of steps taken in 24hours (r=-0.47; P=.024). The Spanish version of SGRQ-Ideveloped by our group shows good internal consistency, reproducibility and validity, so it can be used for the evaluation of quality of life (QOL) in IPF patients. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Pulmonary hemodynamics and gas exchange in off pump coronary artery bypass grafting.

PubMed

Vedin, Jenny; Jensen, Ulf; Ericsson, Anders; Samuelsson, Sten; Vaage, Jarle

2005-10-01

To investigate the influence of cardiopulmonary bypass on pulmonary hemodynamics and gas exchange. Low risk patients admitted for elective coronary artery bypass grafting were randomized to either on (n=25) or off pump (n=25) surgery. Central hemodynamics, gas exchange, and venous admixture were studied during and up to 20 h after surgery. There was no difference in pulmonary vascular resistance index (P=0.16), right ventricular stroke work index (P>0.2), mean pulmonary artery pressure (P>0.2) or pulmonary capillary wedge pressure (P>0.2) between groups. Soon after surgery there was a tendency towards higher cardiac index (P=0.07) in the off pump group. Arterial oxygen tension (P>0.2), hematocrit (P>0.2), venous admixture (P>0.2), and arterial-venous oxygen content difference (P=0.12) did not differ between groups. This prospective, randomized study showed no difference in pulmonary hemodynamics, pulmonary gas exchange, and venous admixture, in low risk patients undergoing off pump compared to on pump coronary artery bypass surgery.

Social deprivation and prognosis in Scottish patients with pulmonary arterial hypertension.

PubMed

Pellino, Katherine; Kerridge, Simon; Church, Colin; Peacock, Andrew J; Crowe, Timothy; Jayasekera, Geeshath; Johnson, Martin K; MacKenzie, Alison M

2018-02-01

Several demographic and clinical factors have prognostic significance in idiopathic pulmonary arterial hypertension (IPAH). Studies in China and the USA have suggested an association between low socioeconomic status and reduced survival. The impact of social deprivation on IPAH survival in the UK is not known.280 patients with IPAH and hereditary PAH (HPAH) attending the Scottish Pulmonary Vascular Unit (Glasgow, UK) were assigned to social deprivation quintiles using the Scottish Index of Multiple Deprivation database. The association between survival and social deprivation quintile was assessed using Cox proportional hazards regression analysis.The distribution of IPAH/HPAH patients was more socially deprived than would be expected based on Scottish citizenry as a whole (Chi-squared 16.16, p=0.003), suggesting referral and access to care is not impeded by socioeconomic status. Univariate analysis demonstrated no significant association between social deprivation and survival (p=0.81), and this association failed to reach significance with inclusion of time, sex and age as covariates in the model (p=0.23). There were no statistically significant correlations between social deprivation and baseline clinical variables of prognostic importance except for age, sex and quality of life.Social deprivation is not a significant referral barrier or prognostic factor for IPAH and HPAH in Scotland. Copyright ©ERS 2018.

Obstructive sleep apnoea and related comorbidities in incident idiopathic pulmonary fibrosis.

PubMed

Gille, Thomas; Didier, Morgane; Boubaya, Marouane; Moya, Loris; Sutton, Angela; Carton, Zohra; Baran-Marszak, Fanny; Sadoun-Danino, Danielle; Israël-Biet, Dominique; Cottin, Vincent; Gagnadoux, Frederic; Crestani, Bruno; d'Ortho, Marie-Pia; Brillet, Pierre-Yves; Valeyre, Dominique; Nunes, Hilario; Planès, Carole

2017-06-01

The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); 2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h -1 ), with moderate OSA (15 ≤AHI <30 events·h -1 ) and with severe OSA (AHI ≥30 events·h -1 ).The prevalence of moderate-to-severe OSA and severe OSA was 62% and 40%, respectively. AHI did not correlate with demographic or physiological data. All patients with severe OSA had a medical history of CVD, versus 41.2% and 40% of those with no or mild OSA, or with moderate OSA, respectively (p<0.0001). Ischaemic heart disease (IHD) and moderate-to-severe coronary artery calcifications were strongly associated with severe OSA. The 8-OH-DG and matrix metalloproteinase-7 serum levels were significantly increased in the severe OSA group.Moderate-to-severe OSA is highly prevalent in incident IPF and severe OSA is strongly associated with the presence of CVD, particularly IHD. Copyright ©ERS 2017.

Efficacy and adverse events of pirfenidone in treating idiopathic pulmonary fibrosis

PubMed Central

Ren, Hui; Wang, Kai; Yang, Hao; Gao, Lingyun

2017-01-01

Objectives: To analyze the efficacy and adverse events (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for studies published before June 2016. All studies of clinical trials with the key words IPF or idiopathic pulmonary fibrosis or lung fibrosis and pirfenidone or Esbriet were identified. Quality assessment and data extraction were conducted by 2 independent researchers. A meta-analysis of randomized controlled trials (RCTs) was performed, and relative risk (RR) and 95% confidence intervals (95% CIs) were calculated. Results: Five studies were included in this review, involving 1568 participants. The meta-analysis revealed that pirfenidone reduced the risk of decline in forced vital capacity (FVC)% ≥10% from baseline (relative risk: 0.62; 95% CI: 0.51-0.76, p<0.001). The pirfenidone group had a significantly higher rate of AEs compared with the placebo group. Pirfenidone did not reduce mortality from any cause significantly (odds ratio: 0.63; 95% CI: 0.36-1.09). Conclusions: This study showed that pirfenidone could reduce disease progression as assessed by the decline in FVC in IPF. Pirfenidone represents a suitable treatment option for patients with IPF. PMID:28889145

[The role of N-acetylcysteine against the injury of pulmonary artery induced by LPS].

PubMed

Huang, Xin-li; Ling, Yi-ling; Zhu, Tie-nian

2002-11-01

To investigate the alleviating effect of N-acetylcysteine (NAC) on lung injury induced by lipopolysaccharides (LPS) and its mechanism. The effects of NAC on changes of the pulmonary arterial reactivity and the ultrastructure of pulmonary arterial endothelium induced by LPS were observed with the isolated artery ring technique and scanning electron microscope (SEM). Malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD) activity of pulmonary artery tissues were detected. The exposure of pulmonary artery to LPS (4 microg/ml, 7 h) led to reduction of endothelium-dependent relaxation response to acetylcholine (ACh), which was reversed by the concomitant exposure to NAC (0.5 mmol/L, 7 h), whereas NAC itself had no effect on the response. Significant structural injury were observed under SEM in LPS group and alleviated the changes in LPS + NAC group. The MDA, NO contents increased but SOD activity decreased in LPS group, which were reversed by the concomitant exposure to NAC. NAC protects pulmonary artery endothelium and enhances endothelium-dependent relaxation response of pulmonary artery by antioxidation effect, which may be one of the mechanisms of its reversing pulmonary artery hypertension and following lung injury induced by LPS.

Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

PubMed

Rabinovitch, Marlene; Guignabert, Christophe; Humbert, Marc; Nicolls, Mark R

2014-06-20

This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. © 2014 American Heart Association, Inc.

Fatal persistent pulmonary hypertension presenting late in the neonatal period.

PubMed Central

Raine, J; Hislop, A A; Redington, A N; Haworth, S G; Shinebourne, E A

1991-01-01

Two cases of fatal idiopathic persistent pulmonary hypertension presented late in the neonatal period. Lungs were examined histologically by light and electron microscopy, and immunocytochemical studies were used to identify nerves. There was extension of medial smooth muscle distally along the arterial pathway so that most precapillary arteries had completely muscular walls, which in some cases completely obliterated the vessel lumen. Enlarged endothelial cells also contributed to the reduction in the size of the lumen. Nerve fibres accompanying muscular arteries were found in the alveolar region, more distal than is normal. The predominant neuropeptide was the vasoconstrictor tyrosine. Possible aetiological factors in persistent pulmonary hypertension of the newborn are increased muscularity of the peripheral pulmonary arteries antenatally, an increase in the number of vasoconstrictor nerves, or an imbalance in the production of leukotrienes and prostacyclins in the perinatal period. Images Figure 1 Figure 2 Figure 3 PMID:2025031

Detection of patent ductus arteriosus with intraoperative transesophageal echocardiography in a patient undergoing closure of coronary artery to pulmonary artery fistula.

PubMed

Miyata, Yuka; Hayashi, Yukio

2017-01-01

Coronary artery to pulmonary artery fistula is an unusual vascular anomaly, and the shunt ratio of this fistula is usually small. We report anesthetic management of a 55-year-old female with annuloaortic ectasia, aortic valve regurgitation, and coronary artery to pulmonary artery fistula undergoing radical repair. We calculated the left-to-right shunt ratio after placement of a pulmonary artery catheter and found that the ratio was unexpectedly high. Thus, we explored the presence of another shunt by intraoperative transesophageal echocardiography and found patent ductus arteriosus undiagnosed before operation. A combination of a pulmonary artery catheter and transesophageal echocardiography is useful to explore the presence of another shunt, such as patent ductus arteriosus during anesthesia.

Lineage Analysis in Pulmonary Arterial Hypertension

DTIC Science & Technology

2013-06-01

monocrotaline pyrrole . The fate of lacZ-expressing cells will be correlated with immunofluorescent staining of endothelial marker CD31, mesenchymal marker...A) Pilot study: Time course of development of pulmonary hypertension in pneumonectomized mice injected with monocrotaline pyrrole (P/MCTP, n = 4... pyrrole . A, B) Normal muscular pulmonary artery (PA) adjacent to bronchiole (Br) A) hematoxylin and eosin stain (H&E), B) elastin-van Gieson stain (EVG

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

PubMed

Zhang, Yonghong; Xie, Xinming; Zhu, Yanting; Liu, Lu; Feng, Wei; Pan, Yilin; Zhai, Cui; Ke, Rui; Li, Shaojun; Song, Yang; Fan, Yuncun; Fan, Fenling; Wang, Xiaochuang; Li, Fengjuan; Li, Manxiang

2015-01-01

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

Anomalous Left Coronary Artery from the Pulmonary Artery: Masquerading as Peripartum Cardiomyopathy.

PubMed

Frigault, Jonathan; Lafrenière-Bessi, Valérie; Perron, Jean; Bédard, Élisabeth; Philippon, François; Poirier, Paul; Larose, Éric; Jacques, Frédéric

2018-03-09

Diagnosed with peripartum cardiomyopathy 8 years earlier, a 45-year-old female suffered sudden cardiac death. Following resuscitation, the patient was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery and underwent a successful coronary repair. The management of a patient with clinical features of cardiomyopathy is reviewed. Anomalous left coronary artery originating from the pulmonary artery (ALCAPA) is a rare but potentially lethal congenital anomaly affecting 1 in 300,000 live births 1 . Infants may have clinical features of myocardial ischemia and congestive heart failure 2 . Most surgically untreated patients die within the first year of life 3 . Although rare in teenagers and adults, this syndrome can cause sudden cardiac death 3 . ALCAPA that becomes clinically significant in the peripartum period and that is misdiagnosed for a postpartum cardiomyopathy, such as presented herein, is a very rare occurrence. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-04-01

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

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

PubMed Central

Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D

2016-01-01

Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734

11C-Acetate clearance as an index of oxygen consumption of the right myocardium in idiopathic pulmonary arterial hypertension: a validation study using 15O-labeled tracers and PET.

PubMed

Wong, Yeun Ying; Raijmakers, Pieter; van Campen, Jasmijn; van der Laarse, Willem J; Knaapen, Paul; Lubberink, Mark; Ruiter, Gerrina; Vonk Noordegraaf, Anton; Lammertsma, Adriaan A

2013-08-01

Idiopathic pulmonary arterial hypertension (IPAH) results in increased right ventricular (RV) workload and oxygen demand. It has been shown that myocardial oxygen consumption (MVO2) of the hypertrophied right ventricle of IPAH patients can be measured using PET and (15)O-labeled tracers. This method is, however, not very suitable for routine clinical practice. The purpose of the present study was to assess whether MVO2 can also be determined in the right ventricle of IPAH patients from the clearance of (11)C-acetate, a simple method that is in use for MVO2 measurements of the left myocardium. Seventeen of 26 IPAH patients performed the total PET study. Nine other patients were scanned only for (11)C-acetate. (15)O-H2O, (15)O-O2, and (15)O-CO scans were used to derive RV flow, oxygen extraction fraction, and blood volume, respectively, from which RV MVO2 was calculated. The rate of clearance determined by monoexponential curve fitting (K(mono)) and the efflux rate constant k2 were derived from the (11)C-acetate scan. The RV rate-pressure product was also determined by means of right heart catheterization, as an index of the RV MVO2, and was calculated as the product of systolic pulmonary artery pressure and heart rate. Both (11)C-acetate clearance rates, K(mono) (R(2) = 0.41, P = 0.006) and k2 (R(2) = 0.45, P = 0.003), correlated with RV MVO2. They also correlated with RV rate-pressure product (K(mono), R(2) = 0.41, P = 0.0005; k2, R(2) = 0.48, P < 0.0001). (11)C-acetate clearance rates correlated moderately with quantitative RV MVO2 measurements in IPAH. Therefore, (11)C-acetate PET can be used only as an index of RV oxidative metabolism in IPAH patients.

Molecular biomarkers in idiopathic pulmonary fibrosis

PubMed Central

Ley, Brett; Brown, Kevin K.

2014-01-01

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

Pulmonary arterial compliance: How and why should we measure it?

PubMed Central

Ghio, Stefano; Schirinzi, Sandra; Pica, Silvia

2015-01-01

The pulmonary circulation is a high-flow/low-pressure system, coupled with a flow generator chamber–the right ventricle–, which is relatively unable to tolerate increases in afterload. A right heart catheterization, using a fluid-filled, balloon-tipped Swan-Ganz catheter allows the measurement of all hemodynamic parameters characterizing the pulmonary circulation: the inflow pressure, an acceptable estimate the outflow pressure, and the pulmonary blood flow. However, the study of the pulmonary circulation as a continuous flow system is an oversimplification and a thorough evaluation of the pulmonary circulation requires a correct understanding of the load that the pulmonary vascular bed imposes on the right ventricle, which includes static and dynamic components. This is critical to assess the prognosis of patients with pulmonary hypertension or with heart failure. Pulmonary compliance is a measure of arterial distensibility and, either alone or in combination with pulmonary vascular resistance, gives clinicians the possibility of a good prognostic stratification of patients with heart failure or with pulmonary hypertension. The measurement of pulmonary arterial compliance should be included in the routine clinical evaluation of such patients. PMID:26779530

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

PubMed

Su, J; Hilberg, O; Howard, L; Simonsen, U; Hughes, A D

2016-12-01

Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

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

PubMed Central

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

Dependence of Golgi apparatus integrity on nitric oxide in vascular cells: implications in pulmonary arterial hypertension

PubMed Central

Lee, Jason E.; Patel, Kirit; Almodóvar, Sharilyn; Tuder, Rubin M.; Flores, Sonia C.

2011-01-01

Although reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), its consequences on organellar structure and function within vascular cells is largely unexplored. We investigated the effect of reduced NO on the structure of the Golgi apparatus as assayed by giantin or GM130 immunofluorescence in human pulmonary arterial endothelial (HPAECs) and smooth muscle (HPASMCs) cells, bovine PAECs, and human EA.hy926 endothelial cells. Golgi structure was also investigated in cells in tissue sections of pulmonary vascular lesions in idiopathic PAH (IPAH) and in macaques infected with a chimeric simian immunodeficiency virus containing the human immunodeficiency virus (HIV)-nef gene (SHIV-nef) with subcellular three-dimensional (3D) immunoimaging. Compounds with NO scavenging activity including 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), methylene blue, N-acetylcysteine, and hemoglobin markedly fragmented the Golgi in all cell types evaluated as did monocrotaline pyrrole, while LY-83583, sildenafil, fasudil, Y-27632, Tiron, Tempol, or H2O2 did not. Golgi fragmentation by NO scavengers was inhibited by diethylamine NONOate, was evident in HPAECs after selective knockdown of endothelial nitric oxide synthase using small interfering RNA (siRNA), was independent of microtubule organization, required the GTPase dynamin 2, and was accompanied by depletion of α-soluble N-ethylmaleimide-sensitive factor (NSF) acceptor protein (α-SNAP) from Golgi membranes and codispersal of the SNAP receptor (SNARE) Vti1a with giantin. Golgi fragmentation was confirmed in endothelial and smooth muscle cells in pulmonary arterial lesions in IPAH and the SHIV-nef-infected macaque with subcellular 3D immunoimaging. In SHIV-nef-infected macaques Golgi fragmentation was observed in cells containing HIV-nef-bearing endosomes. The observed Golgi fragmentation suggests that NO plays a significant role in

Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

PubMed Central

Tashiro, Jun; Rubio, Gustavo A.; Limper, Andrew H.; Williams, Kurt; Elliot, Sharon J.; Ninou, Ioanna; Aidinis, Vassilis; Tzouvelekis, Argyrios; Glassberg, Marilyn K.

2017-01-01

Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans. PMID:28804709

Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy.

PubMed

Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi

2017-01-01

It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

PubMed

Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich

2017-03-01

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.

The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

PubMed Central

Martinez, Fernando J; Chisholm, Alison; Collard, Harold R; Flaherty, Kevin R; Myers, Jeffrey; Raghu, Ganesh; Walsh, Simon LF; White, Eric S; Richeldi, Luca

2017-01-01

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients. PMID:27932290

Wave reflections in the pulmonary arteries analysed with the reservoir–wave model

PubMed Central

Bouwmeester, J Christopher; Belenkie, Israel; Shrive, Nigel G; Tyberg, John V

2014-01-01

Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow. PMID:24756638

Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients.

PubMed

Liu, Jie; Fei, Lei; Huang, Guang-Qing; Shang, Xiao-Ke; Liu, Mei; Pei, Zhi-Jun; Zhang, Yong-Xue

2018-05-01

Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.

PubMed

Elinoff, Jason M; Rame, J Eduardo; Forfia, Paul R; Hall, Mary K; Sun, Junfeng; Gharib, Ahmed M; Abd-Elmoniem, Khaled; Graninger, Grace; Harper, Bonnie; Danner, Robert L; Solomon, Michael A

2013-04-02

Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include

Aortic Implantation of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery: Long-Term Outcomes.

PubMed

Mongé, Michael C; Eltayeb, Osama; Costello, John M; Sarwark, Anne E; Carr, Michael R; Backer, Carl L

2015-07-01

Since 1989 all patients with anomalous origin of the left coronary artery from the pulmonary artery at our institution have been treated with aortic implantation. The purpose of this review was to assess the late outcomes of these patients, especially regarding left ventricular (LV) function and mitral valve insufficiency. Between 1989 and 2014, 36 patients had aortic implantation of anomalous origin of the left coronary artery from the pulmonary artery. Mean age at surgery was 2.5 ± 5.1 years (median, 0.5 years). Operative strategy included antegrade cold-blood cardioplegia, main pulmonary artery transection, aortic implantation with a large button of pulmonary artery, pulmonary reconstruction with fresh autologous pericardium, and prolonged postoperative inotropic and ventilator support. Mitral regurgitation and LV dysfunction were graded as 0 to 4 (0 = none, 1 = trivial, 1.5 = trivial-mild, 2 = mild, 2.5 = mild-moderate, 3 = moderate, 3.5 = moderate-severe, and 4 = severe). Mean mitral regurgitation grade preoperatively was 2.95 ± 0.95. Mean LV dysfunction grade was 3.14 ± 1.27. Mean cross-clamp and cardiopulmonary bypass times were 49.1 ± 18 minutes (median, 48.5 minutes) and 147.5 ± 45 minutes (median, 139 minutes), respectively. There was no operative or late mortality. Four patients had delayed sternal closure. Mean duration of ventilator support was 11 ± 6.6 days (median, 9 days). Two patients required 3 and 6 days of postoperative extracorporeal mechanical circulatory support. Mean length of stay was 25 ± 18 days (median, 19 days). No patient has required reoperation for supravalvar pulmonary stenosis, coronary stenosis, or mitral valve repair or replacement. Late echocardiographic follow-up shows a mean mitral regurgitation grade of 1.67 ± 1.05 and a mean LV dysfunction grade of 0.23 ± 0.68. Aortic implantation is our procedure of choice for patients with anomalous origin of the left coronary artery from the pulmonary artery. No patient required

Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways

PubMed Central

Evans, Christopher M.; Fingerlin, Tasha E.; Schwarz, Marvin I.; Lynch, David; Kurche, Jonathan; Warg, Laura; Yang, Ivana V.; Schwartz, David A.

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is an incurable complex genetic disorder that is associated with sequence changes in 7 genes (MUC5B, TERT, TERC, RTEL1, PARN, SFTPC, and SFTPA2) and with variants in at least 11 novel loci. We have previously found that 1) a common gain-of-function promoter variant in MUC5B rs35705950 is the strongest risk factor (genetic and otherwise), accounting for 30-35% of the risk of developing IPF, a disease that was previously considered idiopathic; 2) the MUC5B promoter variant can potentially be used to identify individuals with preclinical pulmonary fibrosis and is predictive of radiologic progression of preclinical pulmonary fibrosis; and 3) MUC5B may be involved in the pathogenesis of pulmonary fibrosis with MUC5B message and protein expressed in bronchiolo-alveolar epithelia of IPF and the characteristic IPF honeycomb cysts. Based on these considerations, we hypothesize that excessive production of MUC5B either enhances injury due to reduced mucociliary clearance or impedes repair consequent to disruption of normal regenerative mechanisms in the distal lung. In aggregate, these novel considerations should have broad impact, resulting in specific etiologic targets, early detection of disease, and novel biologic pathways for use in the design of future intervention, prevention, and mechanistic studies of IPF. PMID:27630174

[Total cavopulmonary connection for grown diminutive pulmonary artery after staged Blalock-Taussig shunt].

PubMed

Uchita, S; Matsuo, K; Ishida, T; Okajima, Y; Aotsuka, H; Fujiwara, T

1998-11-01

We report a two-year-old girl with asplenia, [A, L, L] DORV, pulmonary atresia, common AV valve, PDA, and TAPVC, who successfully underwent total cavo pulmonary connection (TCPC). Deep cyanosis was pointed out since birth. Cardiac catheterization performed on the sixth day after birth revealed a diminutive pulmonary artery tree of which PA index was 41 mm2/m2. Left modified Blalock-Taussig shunt was created at 27 days of age. The PA index increased to 282 mm2/mm2, but disparity in diameter between the left and the right pulmonary artery was yielded by PDA subsidence. Therefore additional contralateral B-T shunt was made at one year of age. Follow-up cardiac catheterization at 28 months of age showed well developed pulmonary artery; PA index of 460 mm2/m2, right pulmonary resistance (Rp) of 3.49 units, left Rp of 2.33 units, and estimated total Rp was 1.39. According to study, bidirectional Glenn procedure or TCPC was indicated. Considering necessity of urgent repair of common pulmonary vein obstruction, regurgitation of the common atrio-ventricular valve and pulmonary artery stenosis, TCPC was performed with concomitant repair of the associated lesions. Severe butterfly-figure stenosis of the central PA was augmented by anastomosing both the left SVC and the left-sided atrium. In conclusion, diminutive pulmonary artery could be adequately grown by phase-in Blalock-Taussig shunts. Pulmonary blood flow scintigraphy was thought to be useful for estimation of pulmonary resistance in such cases with different pulmonary resistance between right and left PA.

CT Findings of Ruptured Intramural Hematoma of the Aorta Extending Along the Pulmonary Artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sueyoshi, Eijun, E-mail: EijunSueyoshi@aol.com; Sakamoto, Ichiro; Uetani, Masataka

Mediastinal hematoma extending along the pulmonary artery is a rare complication of Stanford type A classic (double-barreled) aortic dissection. Rupture from the posterior aspect of the aortic root penetrates the shared adventitia of the aorta and pulmonary artery. From this location, hematoma can spread along the adventitial planes of the pulmonary arteries out into the lungs. We report a case of ruptured intramural hematoma of the aorta (IMH) extending along the pulmonary artery. To our knowledge, this finding in patients with IMH has not been reported in the literature.

An unusual neonatal presentation of anomalous origin of the left coronary artery arising from the pulmonary artery.

PubMed

Garty, Y; Guri, A; Shinwell, E S; Matitiau, A

2008-01-01

We describe a previously unreported neonatal presentation of an anomalous origin of the left coronary artery arising from the pulmonary artery. This is a full-term female infant after normal pregnancy and delivery. The baby was diagnosed at 2 days of age due to weak femoral pulses noted on the routine nursery discharge examination. The cardiac examination revealed weak pulses everywhere and mild tachypnea and tachycardia. An electrocardiogram showed clear signs of ischemia. Echocardiography demonstrated an anomalous origin of the left coronary artery arising from the pulmonary artery with bidirectional blood flow. There was a severely depressed left ventricular function and mild mitral valve regurgitation. At 4 days of age, the infant underwent complete successful surgical repair with reimplantation of the anomalous coronary artery to the aorta. She recovered slowly but well. Fifteen months later she is doing well with no cardiac residua. A neonatal presentation is very unusual due to protective high pulmonary resistance after birth, with gradual decline in pressure and gradual onset of heart failure. This case may be related to an unusually rapid drop in pulmonary vascular resistance causing very early cardiac ischemia. (c) 2007 S. Karger AG, Basel.

RV stroke work in children with pulmonary arterial hypertension: estimation based on invasive haemodynamic assessment and correlation with outcomes.

PubMed

Di Maria, Michael V; Younoszai, Adel K; Mertens, Luc; Landeck, Bruce F; Ivy, D Dunbar; Hunter, Kendall S; Friedberg, Mark K

2014-09-01

RV performance is an important determinant of outcomes in children with pulmonary arterial hypertension (PAH). RV stroke work (RVSW), the product of mean pulmonary artery pressure and stroke volume, integrates contractility, afterload and ventricular-vascular coupling. RVSW has not been evaluated in children with PAH. We tested the hypothesis that RVSW would be a predictor of outcomes in children with PAH. Patients in the Children's Hospital Colorado PAH database were evaluated retrospectively, and those with idiopathic PAH and those with minor or repaired congenital heart disease were included. Haemodynamic data were obtained by catheterisation and echocardiography, performed within 3 months. RVSW was calculated: mean pulmonary arterial pressure × stroke volume, and indexed to body surface area. Statistics included Kruskal-Wallis, Wilcoxon rank sum, and Spearman correlation. Fifty patients were included. Median age of the cohort was 9.5 (6.0, 15.7) years, with a median indexed pulmonary vascular resistance (PVRi) of 6.5 (3.7, 11.6) WU m(2). RVSW had a significant association with PVRi (r=0.6, p<0.0001), tricuspid annular systolic plane excursion (r=0.55, p=0.0001), and RV fractional area change (r=-0.4, p=0.005). Grouped by WHO class, there was a significant difference in RVSW (p=0.04). Need for atrial septostomy and death were associated with higher RVSW (p=0.04 and p=0.03, respectively). RVSW can be estimated in children with PAH, and is significantly associated with abnormal WHO class, the need for septostomy, as well as mortality. Indices accounting for RV performance as well as ventricular-vascular coupling may be useful in the prognosis and, hence, management of children with PAH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Efficacy and adverse events of pirfenidone in treating idiopathic pulmonary fibrosis.

PubMed

Ren, Hui; Wang, Kai; Yang, Hao; Gao, Lingyun

2017-09-01

To analyze the efficacy and adverse events  (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for studies published before June 2016. All studies of clinical trials with the key words IPF or idiopathic pulmonary fibrosis or lung fibrosis and pirfenidone or Esbriet were identified. Quality assessment and data extraction nwere conducted by 2 independent researchers. A meta-analysis of randomized controlled trials (RCTs) was performed, and relative risk (RR) and 95% confidence intervals (95% CIs) were calculated.   Results: Five studies were included in this review, involving 1568 participants. The meta-analysis revealed that pirfenidone reduced the risk of decline in forced vital capacity (FVC)% ≥10% from baseline (relative risk: 0.62; 95% CI: 0.51-0.76, p less than 0.001). The pirfenidone group had a significantly higher rate of AEs compared with the placebo group. Pirfenidone did not reduce mortality from any cause significantly (odds ratio: 0.63; 95% CI: 0.36-1.09). Conclusions: This study showed that pirfenidone could reduce disease progression as assessed by the decline in FVC in IPF. Pirfenidone represents a suitable treatment option for patients with IPF.

Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.

PubMed

Ogura, Takashi; Taniguchi, Hiroyuki; Azuma, Arata; Inoue, Yoshikazu; Kondoh, Yasuhiro; Hasegawa, Yoshinori; Bando, Masashi; Abe, Shinji; Mochizuki, Yoshiro; Chida, Kingo; Klüglich, Matthias; Fujimoto, Tsuyoshi; Okazaki, Kotaro; Tadayasu, Yusuke; Sakamoto, Wataru; Sugiyama, Yukihiko

2015-05-01

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone. Copyright ©ERS 2015.

Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog

PubMed Central

Nicolle, Audrey P.; Chetboul, Valérie; Tessier-Vetzel, Dominique; Sampedrano, Carolina Carlos; Aletti, Edouard; Pouchelon, Jean-Louis

2006-01-01

A dog was presented with a history of dyspnea, coughing, and ascites. Angiostrongylosis and severe pulmonary arterial hypertension (PAH) were found, as well as a marked discordance between the electrical and mechanical events of the heart. Pulmonary arterial hypertension related to Angiostrongylus vasorum has rarely been reported. PMID:16933559

Integrated care and optimal management of pulmonary arterial hypertension

PubMed Central

Strange, Geoff; Fowler, Robin; Jary, Corina; Dalton, Brad; Stewart, Simon; Gabbay, Eli

2009-01-01

Pulmonary arterial hypertension (PAH) may occur as an idiopathic process or as a component of a variety of diseases, including connective tissue diseases, congenital heart disease, and exposure to appetite suppressants or infectious agents such as HIV. Untreated, it is a potentially devastating disease; however, diagnosis can be difficult due to the non-specific nature of symptoms during the early stages, and the fact that patients often present to a range of different medical specialties. The past decade has seen remarkable improvements in our understanding of the pathology associated with the condition and the development of PAH-specific therapies with the ability to alter the natural history of the disease. This article reviews the evidence for screening and diagnosis of susceptible patient groups and discusses treatment selection and recommendations based on data available from randomized controlled trials. In addition, due to the complexity of the diagnostic evaluation required and the treatment options available, this review mandates for a multidisciplinary approach to the management of PAH. We discuss the roles and organizational structure of a specialized PAH center in Perth, Western Australia to highlight these issues. PMID:21197349

Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

PubMed

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-03-16

Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

Modified Lung Ultrasonographic Technique for Evaluation of Idiopathic Pulmonary Fibrosis: Lateral Decubitus Position.

PubMed

Vassalou, Evangelia E; Raissaki, Maria; Magkanas, Eleftherios; Antoniou, Katerina M; Karantanas, Apostolos H

2017-12-01

To compare lung ultrasonography (US) in the sitting or supine positions and the lateral decubitus position, with regard to the feasibility, duration, patient convenience, and assessment of B-lines, in patients with idiopathic pulmonary fibrosis. Twenty consecutive patients with idiopathic pulmonary fibrosis were prospectively enrolled. Lung US included scanning of 56 intercostal spaces. Each patient was examined twice by 2 protocols. During protocol 1, patients were examined in the supine and sitting positions for the anterior and dorsal chest, respectively. During protocol 2, patients were examined in the left lateral decubitus position for the evaluation of the right hemithorax and the reverse. Total, anterior, and posterior US scores resulted from the sum of B-lines at the whole, anterior, and posterior chest, respectively. High-resolution computed tomography (CT) was considered the reference standard. The duration of each protocol was recorded. Patients were questioned about which protocol they preferred. There was no difference regarding feasibility between the protocols. A significant correlation was found between total US scores for both protocols and high-resolution CT findings (P < .0001), with protocol 2 showing a slightly higher correlation. A positive correlation was found between the protocols regarding total, anterior, and posterior US scores (P < .0001). The mean duration of protocol 2 was less than that of protocol 1 (P < .005). Nineteen patients (95%) reported a preference for protocol 2. Lung US in the lateral decubitus position seems to be faster and more convenient. There appears to be no difference regarding feasibility and the number of B-lines, whereas it shows slightly higher correlation with high-resolution CT, compared with the sitting or supine positions in patients with idiopathic pulmonary fibrosis. © 2017 by the American Institute of Ultrasound in Medicine.

Superior Vena Cava Stent Migration into the Pulmonary Artery Causing Fatal Pulmonary Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, Girija, E-mail: gijanandm@hotmail.com; Lewanski, Conrad R.; Cowman, Steven A.

2011-02-15

Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.

Lung Fibroblasts, Aging, and Idiopathic Pulmonary Fibrosis.

PubMed

Pardo, Annie; Selman, Moisés

2016-12-01

Idiopathic pulmonary fibrosis (IPF) is an aging-associated, progressive, and irreversible lung disease of unknown etiology, elusive pathogenesis, and very limited therapeutic options. The hallmarks of IPF are aberrant activation of alveolar epithelial cells and accumulation of fibroblasts and myofibroblasts along with excessive production of extracellular matrix. The linkage of aging with this disorder is uncertain, but a number of changes associated with aging, including telomere attrition, cell senescence, and mitochondrial dysfunction, have been revealed in IPF lungs. Also, aging seems to confer a profibrotic phenotype upon fibroblasts and to increase the severity of the fibrogenic response in non-IPF fibrotic lung disorders. Better knowledge of the pathophysiological mechanisms linking aging to IPF will advance understanding of its pathogenesis and may provide new therapeutic windows to treatment of this devastating disease.

Current approaches to the management of idiopathic pulmonary fibrosis.

PubMed

Raghu, Ganesh; Richeldi, Luca

2017-08-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF. In addition to pharmacological therapy, optimal management of IPF includes treatment of comorbidities, symptom relief, pulmonary rehabilitation, and palliative care. Patient education is important to enable patients to make decisions about their care and to help them manage their disease and the side-effects of anti-fibrotic drugs. Research continues into new treatments and combinations of treatments that may improve outcomes for patients with this devastating disease. Copyright © 2017. Published by Elsevier Ltd.

Autonomic nervous system involvement in pulmonary arterial hypertension.

PubMed

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

2017-12-04

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

Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.

PubMed

Xie, Liangdi; Lin, Peisen; Xie, Hong; Xu, Changsheng

2010-01-01

Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.

Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

PubMed

van Zeller, Mafalda; Mota, Patrícia Caetano; Amorim, Adelina; Viana, Paulo; Martins, Paula; Gaspar, Luís; Hespanhol, Venceslau; Gomes, Isabel

2012-01-01

Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

PubMed

Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Graham, Shannon; Tillson, D Michael; Barney, Sharron

2017-10-01

Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

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

PubMed

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

PubMed Central

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-07-01

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

[Diagnosis and treatment of pulmonary hypertension].

PubMed

Román, J Sánchez; Hernández, F J García; Palma, M J Castillo; Medina, C Ocaña

2008-03-01

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or another drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment.

New Concepts in the Invasive and Non Invasive Evaluation of Remodelling of the Right Ventricle and Pulmonary Vasculature in Pulmonary Arterial Hypertension

PubMed Central

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

2009-01-01

Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037

Distinctive metabolomic fingerprint in scleroderma patients with pulmonary arterial hypertension.

PubMed

Deidda, Martino; Piras, Cristina; Cadeddu Dessalvi, Christian; Locci, Emanuela; Barberini, Luigi; Orofino, Susanne; Musu, Mario; Mura, Mario Nicola; Manconi, Paolo Emilio; Finco, Gabriele; Atzori, Luigi; Mercuro, Giuseppe

2017-08-15

Pulmonary arterial hypertension (PAH) in systemic sclerosis (SS) identifies a poor prognosis subset of patients. Recent studies suggested a "metabolic theory" on the development of pulmonary arterial hypertension. On this basis we performed a metabolomic study in order to evaluate whether differences in pulmonary arterial blood metabolites were identifiable in SS patients with increased pulmonary vascular resistance (PVR). We studied 18 SS patients (age 58.7±15.6years) free of pulmonary fibrosis who underwent a right heart catheterization (RHC). A blood sample was collected during the RHC in the distal peripheral circulation of the pulmonary arteries to perform the metabolomic analysis. Based on PVR we divided the population into Group A (n=8; PVR=1.16±0.23WU) and Group B (n=10; PVR=2.67±0.67WU; p<0.001 vs Group A). No significant differences were identified in terms of anthropometric, clinical, echo and therapeutic characteristics. At RHC the 2 groups showed a difference in mean pulmonary pressure values (Group A: 20±4mmHg; Group B: 27±3.4mmHg; p=0.03), with mild PAH in Group B. We applied an OSC-PLS-DA with a clear clusterization; SSc patients with PAH showed an increase in acetate, alanine, lactate, and lipoprotein levels and a decrease in γ-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels CONCLUSIONS: Our results suggest that, despite similar clinical and disease-related parameters, SSc patients who develop PAH have an unfavorable metabolic profile able to cause an impaired production of metabolites with protective effects on endothelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

New insights in the treatment strategy for pulmonary arterial hypertension.

PubMed

Sahara, Makoto; Takahashi, Toshiyuki; Imai, Yasushi; Nakajima, Toshiaki; Yao, Atsushi; Morita, Toshihiro; Hirata, Yasunobu; Nagai, Ryozo

2006-10-01

Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

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

PubMed

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.

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

PubMed

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.

Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Dongmin; Perros, Frédéric; Caramori, Gaetano

Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclearmore » in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.« less

Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

PubMed

Ghasemzadeh, Nima; Patel, Riyaz S; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Manocha, Pankaj; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Jones, Dean P; Quyyumi, Arshed A

2014-06-01

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

Coronary Artery Bypass Grafting for an Anomalous Left Coronary Artery from the Pulmonary Artery in a 73-Year-Old Female.

PubMed

Ishida, Narihiro; Shimabukuro, Katsuya; Ogura, Hiroki; Takemura, Hirofumi; Doi, Kiyoshi

2016-06-01

Anomalous left coronary artery from the pulmonary artery (ALCAPA) in adults is a rare congenital coronary abnormality. We report a case of ALCAPA in a 73-year-old female managed by total arterial revascularization. doi: 10.1111/jocs.12755 (J Card Surg 2016;31:380-382). © 2016 Wiley Periodicals, Inc.

Pulmonary hypertension in chronic obstructive pulmonary disease.

PubMed

Weitzenblum, Emmanuel; Chaouat, Ari; Kessler, Romain

2013-01-01

Pulmonary hypertension (PH) is a common complication of advanced chronic obstructive pulmonary disease (COPD) and is defined by a mean pulmonary artery pressure (PAP) ≥ 25 mm Hg at rest in the supine position. Owing to its frequency, COPD is a common cause of PH; in fact, it is the second most frequent cause of PH, just after left heart diseases. PH is due to the elevation of pulmonary vascular resistance, which is caused by functional and morphological factors, chronic alveolar hypoxia being the most important. In COPD PH is generally mild to moderate, PAP usually ranging between 25 and 35 mm Hg in a stable state of the disease. A small proportion of COPD patients may present a severe or "disproportionate" PH with a resting PAP > 35-40 mm Hg. The prognosis is particularly poor in these patients. In COPD PH worsens during exercise, sleep and severe exacerbations of the disease, and these acute increases in afterload may favour the development of right heart failure. The diagnosis of PH relies on Doppler echocardiography, and right heart catheterization is needed in a minority of patients. Treatment of PH in COPD relies on long-term oxygen therapy (≥ 16h/day) which generally stabilizes or at least attenuates the progression of PH. Vasodilator drugs, which are commonly used in idiopathic pulmonary arterial hypertension, have rarely been used in COPD, and we lack studies in this field. Patients with severe PH should be referred to a specialist PH centre where the possibility of inclusion in a controlled clinical trial should be considered.

Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature

PubMed Central

Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

2015-01-01

Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature. PMID:25717357

Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature.

PubMed

Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

2015-02-26

Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature.

Physical Activity and Symptoms in Pulmonary Arterial Hypertension.

PubMed

Matura, Lea Ann; Shou, Haochang; Fritz, Jason S; Smith, K Akaya; Vaidya, Anjali; Pinder, Diane; Archer-Chicko, Christine; Dubow, Danielle; Palevsky, Harold I; Sommers, Marilyn S; Kawut, Steven M

2016-07-01

Fatigue is a common symptom in patients with pulmonary arterial hypertension (PAH); however, the impact of fatigue on daily physical activity in PAH is unknown. Accelerometry is a validated measure for assessing physical activity. We hypothesized that patients with PAH reporting higher levels of fatigue would have lower daily physical activity measured by accelerometry. We performed a prospective cohort study of 15 women with PAH. On day 1, subjects completed the Multidimensional Fatigue Inventory (MFI), the United States Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR), and a 6-min walk test. Subjects wore the accelerometer on their dominant hip and completed an activity diary for 7 days. On day 15, subjects repeated the MFI and the US CAMPHOR, and then wore the accelerometer and completed an activity diary for an additional 7 days. All multivariate analyses were adjusted for age, BMI, and PAH type. The mean age was 50.5 years, and 53% had idiopathic or heritable PAH. During the 2 weeks, subjects were mostly sedentary (85% of the time), although 10% of their time was spent performing low-level activity. Lower average daily counts were associated with worse self-reported energy levels, whereas less day-to-day physical activity variability was associated with more self-reported mental fatigue, physical fatigue, and total activity. Higher percentage of activity bouts was also associated with worse energy. Women with PAH may spend most of their time being sedentary, and lower self-reported energy levels are associated with less daily activity. Interventions to improve symptoms such as fatigue may also increase physical activity levels in PAH. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease

PubMed Central

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K. Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation. PMID:28321059

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

PubMed

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Morphometry-based impedance boundary conditions for patient-specific modeling of blood flow in pulmonary arteries.

PubMed

Spilker, Ryan L; Feinstein, Jeffrey A; Parker, David W; Reddy, V Mohan; Taylor, Charles A

2007-04-01

Patient-specific computational models could aid in planning interventions to relieve pulmonary arterial stenoses common in many forms of congenital heart disease. We describe a new approach to simulate blood flow in subject-specific models of the pulmonary arteries that consists of a numerical model of the proximal pulmonary arteries created from three-dimensional medical imaging data with terminal impedance boundary conditions derived from linear wave propagation theory applied to morphometric models of distal vessels. A tuning method, employing numerical solution methods for nonlinear systems of equations, was developed to modify the distal vasculature to match measured pressure and flow distribution data. One-dimensional blood flow equations were solved with a finite element method in image-based pulmonary arterial models using prescribed inlet flow and morphometry-based impedance at the outlets. Application of these methods in a pilot study of the effect of removal of unilateral pulmonary arterial stenosis induced in a pig showed good agreement with experimental measurements for flow redistribution and main pulmonary arterial pressure. Next, these methods were applied to a patient with repaired tetralogy of Fallot and predicted insignificant hemodynamic improvement with relief of the stenosis. This method of coupling image-based and morphometry-based models could enable increased fidelity in pulmonary hemodynamic simulation.

[Pulmonary arterial hypertension in women].

PubMed

Sanchez, O; Marié, E; Lerolle, U; Wermert, D; Israël-Biet, D; Meyer, G

2008-04-01

Pulmonary arterial hypertension (PAH) is a rare condition characterized by sustained elevation in pulmonary arterial resistance leading to right heart failure. PAH afflicts predominantly women. Echocardiography is the initial investigation of choice for non-invasive detection of PAH but right-heart catheterization is necessary to confirm the diagnosis. Conventional treatment includes non-specific drugs (warfarin, diuretics, oxygen). The endothelin-1 receptor antagonist bosentan, the phosphodiesterase-5 inhibitor sildenafil, and prostanoids have been shown to improve symptoms, exercise capacity and haemodynamics. Intravenous prostacyclin is the first-line treatment for the most severely affected patients. Despite the most modern treatment the overall mortality rate of pregnant women with severe PAH remains high. Therefore, pregnancy is contraindicated in women with PAH and an effective method of contraception is recommended in women of childbearing age. Therapeutic abortion should be offered, particularly when early deterioration occurs. If this option is not accepted, intravenous prostacyclin should be considered promptly. Recent advances in the management of PAH have markedly improved prognosis and have resulted in more women of childbearing age considering pregnancy. A multidisciplinary approach should give new insights into cardiopulmonary, obstetric and anaesthetic management during pregnancy, delivery and the post-partum period.

Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.

PubMed

Boucly, Athénaïs; Weatherald, Jason; Savale, Laurent; Jaïs, Xavier; Cottin, Vincent; Prevot, Grégoire; Picard, François; de Groote, Pascal; Jevnikar, Mitja; Bergot, Emmanuel; Chaouat, Ari; Chabanne, Céline; Bourdin, Arnaud; Parent, Florence; Montani, David; Simonneau, Gérald; Humbert, Marc; Sitbon, Olivier

2017-08-01

Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min -1 ·m -2 1017 patients were included (mean age 57 years, 59% female, 75% idiopathic PAH). After a median follow-up of 34 months, 238 (23%) patients had died. Each of the four low-risk criteria independently predicted transplant-free survival at first re-evaluation. The number of low-risk criteria present at diagnosis (p<0.001) and at first re-evaluation (p<0.001) discriminated the risk of death or lung transplantation. In addition, in a subgroup of 603 patients with brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements, the number of three noninvasive criteria (WHO/NYHA functional class, 6MWD and BNP/NT-proBNP) present at first re-evaluation discriminated prognostic groups (p<0.001).A simplified risk assessment tool that quantifies the number of low-risk criteria present accurately predicted transplant-free survival in PAH. Copyright ©ERS 2017.

Coil embolization for pulmonary artery injury caused by chest tube drainage.

PubMed

Shigefuku, Shunsuke; Kudo, Yujin; Saguchi, Toru; Maeda, Junichi

2017-05-01

Pulmonary artery injury caused by chest tube drainage is rare, but it requires prompt diagnosis to perform urgent surgical repair. We report that a 53-year-old man who suffered from pulmonary artery injury by chest tube drainage was successfully treated by coil embolization. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

PubMed

Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M

2017-07-01

Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected

Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

PubMed Central

Cork, David P.; Mehrotra, Amit K.; Gomberg-Maitland, Mardi

2012-01-01

Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease. PMID:23130109

Lung Ultrasonography in Patients With Idiopathic Pulmonary Fibrosis: Evaluation of a Simplified Protocol With High-Resolution Computed Tomographic Correlation.

PubMed

Vassalou, Evangelia E; Raissaki, Maria; Magkanas, Eleftherios; Antoniou, Katerina M; Karantanas, Apostolos H

2018-03-01

To compare a simplified ultrasonographic (US) protocol in 2 patient positions with the same-positioned comprehensive US assessments and high-resolution computed tomographic (CT) findings in patients with idiopathic pulmonary fibrosis. Twenty-five consecutive patients with idiopathic pulmonary fibrosis were prospectively enrolled and examined in 2 sessions. During session 1, patients were examined with a US protocol including 56 lung intercostal spaces in supine/sitting (supine/sitting comprehensive protocol) and lateral decubitus (decubitus comprehensive protocol) positions. During session 2, patients were evaluated with a 16-intercostal space US protocol in sitting (sitting simplified protocol) and left/right decubitus (decubitus simplified protocol) positions. The 16 intercostal spaces were chosen according to the prevalence of idiopathic pulmonary fibrosis-related changes on high-resolution CT. The sum of B-lines counted in each intercostal space formed the US scores for all 4 US protocols: supine/sitting and decubitus comprehensive US scores and sitting and decubitus simplified US scores. High-resolution CT-related Warrick scores (J Rheumatol 1991; 18:1520-1528) were compared to US scores. The duration of each protocol was recorded. A significant correlation was found between all US scores and Warrick scores and between simplified and corresponding comprehensive scores (P < .0001). Decubitus simplified US scores showed a slightly higher correlation with Warrick scores compared to sitting simplified US scores. Mean durations of decubitus and sitting simplified protocols were 4.76 and 6.20 minutes, respectively (P < .005). Simplified 16-intercostal space protocols correlated with comprehensive protocols and high-resolution CT findings in patients with idiopathic pulmonary fibrosis. The 16-intercostal space simplified protocol in the lateral decubitus position correlated better with high-resolution CT findings and was less time-consuming compared to the

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

PubMed Central

Shah, Shilpa; Szmuszkovicz, Jacqueline R.

2017-01-01

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

Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

PubMed

Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

2016-02-23

Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459. �

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

PubMed

Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

2017-08-01

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Profiling the role of mammalian target of rapamycin in the vascular smooth muscle metabolome in pulmonary arterial hypertension

PubMed Central

Kudryashova, Tatiana V.; Goncharov, Dmitry A.; Pena, Andressa; Ihida-Stansbury, Kaori; DeLisser, Horace; Kawut, Steven M.

2015-01-01

Abstract Increased proliferation and resistance to apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs), coupled with metabolic reprogramming, are key components of pulmonary vascular remodeling, a major and currently irreversible pathophysiological feature of pulmonary arterial hypertension (PAH). We recently reported that activation of mammalian target of rapamycin (mTOR) plays a key role in increased energy generation and maintenance of the proliferative, apoptosis-resistant PAVSMC phenotype in human PAH, but the downstream effects of mTOR activation on PAH PAVSMC metabolism are not clear. Using liquid and gas chromatography–based mass spectrometry, we performed pilot metabolomic profiling of human microvascular PAVSMCs from idiopathic-PAH subjects before and after treatment with the selective adenosine triphosphate–competitive mTOR inhibitor PP242 and from nondiseased lungs. We have shown that PAH PAVSMCs have a distinct metabolomic signature of altered metabolites—components of fatty acid synthesis, deficiency of sugars, amino sugars, and nucleotide sugars—intermediates of protein and lipid glycosylation, and downregulation of key biochemicals involved in glutathione and nicotinamide adenine dinucleotide (NAD) metabolism. We also report that mTOR inhibition attenuated or reversed the majority of the PAH-specific abnormalities in lipogenesis, glycosylation, glutathione, and NAD metabolism without affecting altered polyunsaturated fatty acid metabolism. Collectively, our data demonstrate a critical role of mTOR in major PAH PAVSMC metabolic abnormalities and suggest the existence of de novo lipid synthesis in PAVSMCs in human PAH that may represent a new, important component of disease pathogenesis worthy of future investigation. PMID:26697174

Pulmonary Artery Aneurysm/Pseudoaneurysm, a Delayed Complication of Lung Abscess: A Case Report.

PubMed

Oguma, Tsuyoshi; Morise, Masahiro; Harada, Kazuki; Tanaka, Jun; Sato, Masako; Horio, Yukihiro; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Hayama, Naoki; Aoki, Takuya; Urano, Tetsuya; Ito, Chihiro; Koizumi, Jun; Asano, Koichiro

2015-09-20

Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection. A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan. Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels.

Cardiorespiratory adaptation in a 6-minute walk test by fibrotic idiopathic interstitial pneumonia patients who did or did not respond to pulmonary rehabilitation.

PubMed

Chéhère, Baptiste; Bougault, Valérie; Chenivesse, Cécile; Grosbois, Jean-Marie; Wallaert, Benoit

2018-06-14

Pulmonary rehabilitation (PR) improves performance in the 6-min walk test (6MWT) in a subset of patients with fibrotic idiopathic interstitial pneumonia (f-IIP); however, a large proportion of patients do not respond to PR. To investigate the effects of a PR program on cardiorespiratory responses during a 6MWT and to identify the characteristics of patients who do not show improved performance after PR. An observational study. Patients were recruited from the Competence Centre for Rare Pulmonary Diseases at Lille University Hospital, France and completed an 8-week home-based PR program. A total of 19 patients with f-IIP; 12 with idiopathic pulmonary fibrosis (IPF) and 7 with fibrotic non-specific interstitial pneumonia. Patients underwent spirometry and completed a 6MWT before and after an 8- week PR program. Gas exchange, heart rate, and pulse O2 saturation were measured continuously during the 6MWT. Quality of life, dyspnoea, and anxiety/depression were assessed using the Short-Form 36 (SF-36), the baseline/transition dyspnoea index (BDI/TDI), and the Hospital Anxiety and Depression Scale (HADS) questionnaires. Patients who did and did not improve the distance walked in the 6MWT by at least 30 m after PR were classified as responders (n=9) and non-responders (n=10), respectively. O2 uptake, ventilation rate, and distance covered during the 6MWT were significantly improved only in the responder group (p<0.05). Changes in SF-36, BDI/TDI, and HADS scores did not differ significantly between responders and non-responders. The non-responder group contained significantly more patients with IPF (p<0.05) and experienced greater arterial oxygen desaturation during the 6MWT compared with the responder group. Failure to improve performance in the 6MWT after PR was associated with a diagnosis of IPF, non-improvement in gas exchange, and greater arterial oxygen desaturation. Most f-IIP patients who did not respond to PR were diagnosed with IPF and displayed greater hypoxemia

Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial.

PubMed

Simonneau, Gérald; Rubin, Lewis J; Galiè, Nazzareno; Barst, Robyn J; Fleming, Thomas R; Frost, Adaani E; Engel, Peter J; Kramer, Mordechai R; Burgess, Gary; Collings, Lorraine; Cossons, Nandini; Sitbon, Olivier; Badesch, David B

2008-10-21

Oral sildenafil and intravenous epoprostenol have independently been shown to be effective in patients with pulmonary arterial hypertension. To investigate the effect of adding oral sildenafil to long-term intravenous epoprostenol in patients with pulmonary arterial hypertension. A 16-week, double-blind, placebo-controlled, parallel-group study. Multinational study at 41 centers in 11 countries from 3 July 2003 to 27 January 2006. 267 patients with pulmonary arterial hypertension (idiopathic, associated anorexigen use or connective tissue disease, or corrected congenital heart disease) who were receiving long-term intravenous epoprostenol therapy. Patients were randomly assigned to receive placebo or sildenafil, 20 mg three times daily, titrated to 40 mg and 80 mg three times daily, as tolerated, at 4-week intervals. Of 265 patients who received treatment, 256 (97%) patients (123 in the placebo group and 133 in the sildenafil group) completed the study. Change from baseline in exercise capacity measured by 6-minute walk distance (primary end point) and hemodynamic measurements, time to clinical worsening, and Borg dyspnea score (secondary end points). A placebo-adjusted increase of 28.8 meters (95% CI, 13.9 to 43.8 meters) in the 6-minute walk distance occurred in patients in the sildenafil group; these improvements were most prominent among patients with baseline distances of 325 meters or more. Relative to epoprostenol monotherapy, addition of sildenafil resulted in a greater change in mean pulmonary arterial pressure by -3.8 mm Hg (CI, -5.6 to -2.1 mm Hg); cardiac output by 0.9 L/min (CI, 0.5 to 1.2 L/min); and longer time to clinical worsening, with a smaller proportion of patients experiencing a worsening event in the sildenafil group (0.062) than in the placebo group (0.195) by week 16 (P = 0.002). Health-related quality of life also improved in patients who received combined therapy compared with those who received epoprostenol monotherapy. There was no

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

PubMed

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

2015-04-14

To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). According to the random number table, 24 beagles were randomized into control, PAH and PAH+RSD groups (n=8 each). The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH+RSD groups) were injected. The PAH+RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all P<0.01). The levels of serum angiotensin II (Ang II) and endothelin-1 significantly increased after 8 weeks in PAH dogs ((228±41) vs (113±34) pg/ml and (135±15) vs (77±7) pg/ml, all P<0.01). And Ang II and endothelin-1 were higher in lung tissues of PAH group ((65±10) and (96±10) pg/ml) than in those of control group ((38±7) and (54±6) pg/ml) and PAH+RSD group ((46±8) and (67±9) pg/ml) (all P<0.01). Pulmonary tissues had marked collagen hyperplasia and lamellar corpuscles of type 2 alveolar cells were damaged more severely in PAH dogs than in PAH+RSD dogs. RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

Transesophageal Echocardiographic Assessment of Pulmonary Artery-to-Ascending Aorta Ratio for the Detection of Pulmonary Hypertension in Cardiac Surgical Patients.

PubMed

Narendra Kumar, Karthik; Singh, Naveen G; P S, Nagaraja; Patil, Thimmangouda A; N, Manjunath

2017-10-01

The objective of the study was to investigate if the main pulmonary artery (mPA)-to-ascending aorta (AscAo), (mPA:AscAo) ratio could serve as a screening tool in identifying pulmonary artery hypertension (PAH). A prospective observational study. Tertiary care center, university hospital. Fifty-four adult patients undergoing off-pump coronary artery bypass grafting surgery (OPCAB). mPA and AscAo transverse diameters were measured by transesophageal echocardiography (TEE) and the mean pulmonary arterial pressures (mPAP) were recorded simultaneously using a pulmonary artery catheter. mPA:AscAo ratio demonstrated significant linear correlation with mPAP measured by pulmonary artery catheterization (ie, r = 0.61, confidence interval [CI] = 0.5352-0.6736, p < 0.0001). Receiver operating characteristic curves were performed to evaluate sensitivity and specificity of mPA:AscAo ratio ≥1 for diagnosing PAH (mPAP ≥25 mmHg). Area under the curve for mPA:AscAo ratio was 0.91 (95% CI, 0.869-0.936, p < 0.0001), with a sensitivity of 84.27%, specificity of 83.92%, positive-predictive value of 87.6% and negative-predictive value of 81.1% for a mPAP ≥25 mmHg. The ratio of mPA:AscAo is a simple, reliable, and reproducible method that can be obtained through TEE, which guides the clinician to screen patients with PAH. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Effects of terlipressin on systolic pulmonary artery pressure of patients with liver cirrhosis: An echocardiographic assessment

PubMed Central

Altintas, Engin; Akkus, Necdet; Gen, Ramazan; Helvaci, M. Rami; Sezgin, Orhan; Oguz, Dilek

2004-01-01

AIM: Portopulmonary hypertension is a serious complication of chronic liver disease. Our aim was to search into the effect of terlipressin on systolic pulmonary artery pressure among cirrhotic patients. METHODS: Twelve patients (6 males and 6 females) with liver cirrhosis were recruited in the study. Arterial blood gas samples were obtained in sitting position at rest. Contrast enhanced echocardiography and measurements of systolic pulmonary artery pressure were performed before and after the intravenous injection of 2 mg terlipressin. RESULTS: Of 12 patients studied, the contrast enhanced echocardiography was positive in 5, and the positive findings in contrast enhanced echocardiography were reversed to normal in two after terlipressin injection. The mean systolic pulmonary artery pressure was 25.5 ± 3.6 mmHg before terlipressin injection, and was 22.5 ± 2.5 mmHg after terlipressin (P = 0.003). The systolic pulmonary artery pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin injection, systolic pulmonary artery pressure was < 25 mmHg in four of these cases (58.3% vs 25%, P = 0.04). CONCLUSION: Terlipressin can decrease the systolic pulmonary artery pressure in patients with liver cirrhosis. PMID:15259082

CT measurement of central pulmonary arteries to diagnose pulmonary hypertension (PHTN): more reliable than valid?

PubMed

Terpenning, Silanath; Deng, Matthew; Hong-Zohlman, Susie N; Lin, Cheng Ting; Kligerman, Seth J; Jeudy, Jean; Ketai, Loren H

2016-01-01

The association between main pulmonary artery (MPA) size and pulmonary arterial hypertension (PAHTN) is well established; however, the clinical utility of routine measurement of MPA is uncertain due to considerable overlap between normal patients and those with pulmonary hypertension. The lack of diagnostic accuracy could be further degraded by variability among the radiologists. It is unknown whether the addition of right and left pulmonary artery measurements would improve accuracy or further impair it. The purposes of this study are to verify the accuracy of a proposed cutoff value for the size of MPA in the diagnosis PAHTN, to determine the interrater agreement for this measurement, and to determine whether addition of right pulmonary artery (RPA) and left pulmonary artery (LPA) measurement or simple assessment of patient comorbidities can improve the accuracy. Patients undergoing both cardiac catheterization and chest computed tomography (CT) within 3 months of each other at a large university hospital between January 2010 and December 2012 were identified. Patients with prior cardiac surgery or congenital heart disease and critically ill patients were excluded from the study population. Patients with pericardial disease or severe lung disease documented on CT examinations were also excluded. From the remaining patients, 45 patients with normal pulmonary artery pressure and 50 patients with proven pulmonary hypertension were selected. Demographic data and clinical information was collected from medical records of these patients. Three radiologists with different years of experience in cardiothoracic imaging measured the MPA, RPA, and LPA diameters on axial images using an electronic ruler on 3D work stations independently and were masked to the patient clinical symptoms, diagnosis, and each other's measurement to prevent bias. Association between MPA diameter (MPAD) and patient characteristics assessed by one-way analysis of variance for scalar measures. Each

Coronary artery abnormalities in children with systemic-onset juvenile idiopathic arthritis.

PubMed

Lefèvre-Utile, Alain; Galeotti, Caroline; Koné-Paut, Isabelle

2014-05-01

Still's disease (Systemic-onset Juvenile Idiopathic Arthritis: SoJIA) is characterised by high-spiking daily fevers, arthritis and evanescent rashes. Diagnosis of Still's disease is often challenging. Infectious diseases and other inflammatory conditions, especially in young children, Kawasaki disease may look similar. Clinicians often rely on echocardiographic evidence of coronary artery abnormalities to differentiate between Kawasaki disease and Still's disease. Coronary artery dilation would typically favour the diagnosis of Kawasaki disease. We present four children with Still's disease and coronary artery abnormalities who were initially misdiagnosed as Kawasaki disease. The first patient had pericarditis and an irregular wall of the left coronary artery, without dilation on echocardiography. The second patient had a left coronary artery dilatation and a pericarditis. The third patient had thickened left coronary artery walls, and the fourth patient had a hyperechogenicity of the left and right coronary arteries. They received IVIG without success. The diagnosis of Still's disease was made secondary with evidence of persistent arthritis. All but one patient finally needed biologic treatments. Coronary abnormalities may be observed during various febrile conditions and do not exclude the diagnosis of Still's disease. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Pulmonary function tests correlated with thoracic volumes in adolescent idiopathic scoliosis.

PubMed

Ledonio, Charles Gerald T; Rosenstein, Benjamin E; Johnston, Charles E; Regelmann, Warren E; Nuckley, David J; Polly, David W

2017-01-01

Scoliosis deformity has been linked with deleterious changes in the thoracic cavity that affect pulmonary function. The causal relationship between spinal deformity and pulmonary function has yet to be fully defined. It has been hypothesized that deformity correction improves pulmonary function by restoring both respiratory muscle efficiency and increasing the space available to the lungs. This research aims to correlate pulmonary function and thoracic volume before and after scoliosis correction. Retrospective correlational analysis between thoracic volume modeling from plain x-rays and pulmonary function tests was conducted. Adolescent idiopathic scoliosis patients enrolled in a multicenter database were sorted by pre-operative Total Lung Capacities (TLC) % predicted values from their Pulmonary Function Tests (PFT). Ten patients with the best and ten patients with the worst TLC values were included. Modeled thoracic volume and TLC values were compared before and 2 years after surgery. Scoliosis correction resulted in an increase in the thoracic volume for patients with the worst initial TLCs (11.7%) and those with the best initial TLCs (12.5%). The adolescents with the most severe pulmonary restriction prior to surgery strongly correlated with post-operative change in total lung capacity and thoracic volume (r 2  = 0.839; p < 0.001). The mean increase in thoracic volume in this group was 373.1 cm 3 (11.7%) which correlated with a 21.2% improvement in TLC. Scoliosis correction in adolescents was found to increase thoracic volume and is strongly correlated with improved TLC in cases with severe restrictive pulmonary function, but no correlation was found in cases with normal pulmonary function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:175-182, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[Study on relationship between blood supply from pulmonary artery and pathological characteristics of patients with primary bronchogenic carcinoma].

PubMed

Zhang, Yongkui; Le, Hanbo; Chen, Zhijun; Wang, Chaoye; Zhang, Binjie

2006-01-01

At present, it has been known that the bronchogenic artery participates in the blood supply of primary bronchogenic carcinoma, but there is controversy about the blood supply from pulmonary artery in primary bronchogenic carcinoma. The aim of this study is to assess the relationship between the blood supply from pulmonary artery and pathological characteristis of patients with primary bronchogenic carcinoma. The pulmonary arteries in 43 surgical samples of bronchogenic carcinoma were marked, then the iopromide was used to selective pulmonary arteriography in digital subtraction angiography (DSA). The relationship between tumor with blood supply from pulmonary artery and the pathologic characteristics was observed. There were 34 samples with blood supply from pulmonary artery ( 79.07%) , and 9 samples without blood supply from pulmonary artery (20.93%). The development rate of peripheral lung cancer (100.00%) was significantly higher than that of central lung cancer (64.00%) (P < 0.01) . The development rate of squamous cell carcinoma (91.30%) was remarkably higher than that of adenocarcinoma (61.11%) (P < 0.05). The development rate of poorly differentiated lung cancer (95.00%) was remarkably higher than that of well and moderately differentiated lung cancer (65.22%) (P < 0.05). There was a positive relationship between the tumor size and the development rate (P < 0.05). In primary bronchogenic carcinoma, the pulmonary artery blood supply exists in most of tumors. There is relationship between the blood supply from pulmonary artery and general type, histopathology, cell differentiation and tumor size of lung cancer. The blood supply from pulmonary artery doesn't relate to tumor stage.

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

PubMed

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

2017-01-01

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

IDENTIFICATION OF SPONTANEOUS FELINE IDIOPATHIC PULMONARY FIBROSIS: MORPHOLOGY AND ULTRASTRUCTURAL EVIDENCE FOR A TYPE II PNEUMOCYTE DEFECT

EPA Science Inventory

Abstract
Idiopathic pulmonary fibrosis currently lacks an animal model that develops the persistent, progressive lung fibrosis characteristic of the disease. Sixteen domestic cats developed dyspnea that was not responsive to therapy and which rapidly progressed until death/eu...

Pregnancy in pulmonary arterial hypertension.

PubMed

Olsson, Karen M; Channick, Richard

2016-12-01

Despite advanced therapies, maternal mortality in women with pulmonary arterial hypertension (PAH) remains high in pregnancy and is especially high during the post-partum period. However, recent data indicates that morbidity and mortality during pregnancy and after birth have improved for PAH patients. The current European Society of Cardiology/European Respiratory Society guidelines recommend that women with PAH should not become pregnant. Therefore, the risks associated with pregnancy must be emphasised and counselling offered to women at the time of PAH diagnosis and to women with PAH who become pregnant. Early termination should be discussed. Women who choose to continue with their pregnancy should be treated at specialised pulmonary hypertension centres with experience in managing PAH during and after pregnancy. Copyright ©ERS 2016.

Three-dimensional segmentation of pulmonary artery volume from thoracic computed tomography imaging

NASA Astrophysics Data System (ADS)

Lindenmaier, Tamas J.; Sheikh, Khadija; Bluemke, Emma; Gyacskov, Igor; Mura, Marco; Licskai, Christopher; Mielniczuk, Lisa; Fenster, Aaron; Cunningham, Ian A.; Parraga, Grace

2015-03-01

Chronic obstructive pulmonary disease (COPD), is a major contributor to hospitalization and healthcare costs in North America. While the hallmark of COPD is airflow limitation, it is also associated with abnormalities of the cardiovascular system. Enlargement of the pulmonary artery (PA) is a morphological marker of pulmonary hypertension, and was previously shown to predict acute exacerbations using a one-dimensional diameter measurement of the main PA. We hypothesized that a three-dimensional (3D) quantification of PA size would be more sensitive than 1D methods and encompass morphological changes along the entire central pulmonary artery. Hence, we developed a 3D measurement of the main (MPA), left (LPA) and right (RPA) pulmonary arteries as well as total PA volume (TPAV) from thoracic CT images. This approach incorporates segmentation of pulmonary vessels in cross-section for the MPA, LPA and RPA to provide an estimate of their volumes. Three observers performed five repeated measurements for 15 ex-smokers with ≥10 pack-years, and randomly identified from a larger dataset of 199 patients. There was a strong agreement (r2=0.76) for PA volume and PA diameter measurements, which was used as a gold standard. Observer measurements were strongly correlated and coefficients of variation for observer 1 (MPA:2%, LPA:3%, RPA:2%, TPA:2%) were not significantly different from observer 2 and 3 results. In conclusion, we generated manual 3D pulmonary artery volume measurements from thoracic CT images that can be performed with high reproducibility. Future work will involve automation for implementation in clinical workflows.

Continuous recording of pulmonary artery pressure in unrestricted subjects.

PubMed Central

Ikram, H; Richards, A M; Hamilton, E J; Nicholls, M G

1984-01-01

Continuous ambulatory pulmonary artery pressures were recorded using a conventional No 5 French Goodale-Lubin filled catheter linked to the Oxford Medilog system of a portable transducer-perfusion unit and miniaturised recorder. Data retrieval and analysis were performed using a PB2 Medilog playback unit linked to a PDP 11 computer system. The total system has a frequency response linear to 8 Hz allowing accurate pressure recording over the full range of heart rates. Ten recordings in 10 patients yielded artefact free data for 80% or more of the recorded period. This inexpensive reliable method allows pulmonary artery pressures to be recorded in unrestricted subjects. Images PMID:6704262

Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

PubMed

Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

2017-02-01

A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described. Copyright © 2016 Elsevier B.V. All rights reserved.

Intralober pulmonary sequestration with arterial supply from two different origins: a case report.

PubMed

Erden, Ersin Sukru; Yetim, Tulin Durgun; Balci, Ali; Akcay, Adnan Burak; Hakverdi, Sibel; Demirkose, Mesut

2012-01-01

Pulmonary sequestration is a rare anomaly, which does not have a connection with the bronchial system and gets its blood supply, generally, from the aorta or its branches. Anatomically, two different forms were described: intralobar and extralobar. Although 74% of intralobar pulmonary sequestrations get their blood supply from the descending thoracic aorta, they may get their blood supply from different arteries. Furthermore, there is more than one arterial anomaly in 14.8% of cases. We report an intralobar pulmonary sequestration, in which arterial blood supply is from two different origins (Arcus aorta and celiac trunk). To the best of our knowledge, this is the first case in the literature.

Patient-reported outcomes in idiopathic pulmonary fibrosis research.

PubMed

Swigris, Jeffrey J; Fairclough, Diane

2012-08-01

Patient-reported outcomes (PROs) include questionnaires or surveys that ask patients for their perceptions about things like symptoms they are experiencing or quality of life. For incurable, morbid, life-shortening conditions like idiopathic pulmonary fibrosis (IPF), PROs are particularly germane: They elucidate for clinicians and researchers what it is like for patients to live with such a disease, and they may detect important treatment effects not captured by other metrics (eg, pulmonary physiology). However, a relative paucity of research on PROs in IPF has left significant knowledge gaps in this area and contributed to the timidity investigators have about using PROs as prominent outcomes in IPF drug trials. Additional research on existing instruments is needed to establish or bolster their basic psychometric properties in IPF. When PROs are used as end points in therapeutic trials, analyzing PRO response data can be challenging, but these challenges can be overcome with a transparent, thoughtful, and sophisticated statistical approach. In this article, we discuss some of the basics of PRO assessment, existing knowledge gaps in IPF-related PRO research, and the potential usefulness of using PROs in IPF trials and conclude by offering specific recommendations for an approach to analyzing repeated-measures PRO data from IPF trials.

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

NASA Astrophysics Data System (ADS)

Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

2010-03-01

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

Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

PubMed Central

Voga, Gorazd

2008-01-01

The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed. PMID:18394183

Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

PubMed

Voga, Gorazd

2008-01-01

The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed.

Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis.

PubMed

Borok, Z; Buhl, R; Grimes, G J; Bokser, A D; Hubbard, R C; Holroyd, K J; Roum, J H; Czerski, D B; Cantin, A M; Crystal, R G

1991-07-27

Idiopathic pulmonary fibrosis (IPF) is characterised by alveolar inflammation, exaggerated release of oxidants, and subnormal concentrations of the antioxidant glutathione in respiratory epithelial lining fluid (ELF). Glutathione (600 mg twice daily for 3 days) was given by aerosol to 10 patients with IPF. Total ELF glutathione rose transiently, ELF oxidised glutathione concentrations increased, and there was a decrease in spontaneous superoxide anion release by alveolar macrophages. Thus, glutathione by aerosol could be a means of reversing the oxidant-antioxidant imbalance in IPF.

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

PubMed

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

2015-10-01

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

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults.

PubMed

Yan, C; Zhao, S; Jiang, S; Xu, Z; Huang, L; Zheng, H; Ling, J; Wang, C; Wu, W; Hu, H; Zhang, G; Ye, Z; Wang, H

2007-04-01

Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the

Biaxial Properties of the Left and Right Pulmonary Arteries in a Monocrotaline Rat Animal Model of Pulmonary Arterial Hypertension.

PubMed

Pursell, Erica R; Vélez-Rendón, Daniela; Valdez-Jasso, Daniela

2016-11-01

In a monocrotaline (MCT) induced-pulmonary arterial hypertension (PAH) rat animal model, the dynamic stress-strain relation was investigated in the circumferential and axial directions using a linear elastic response model within the quasi-linear viscoelasticity theory framework. Right and left pulmonary arterial segments (RPA and LPA) were mechanically tested in a tubular biaxial device at the early stage (1 week post-MCT treatment) and at the advanced stage of the disease (4 weeks post-MCT treatment). The vessels were tested circumferentially at the in vivo axial length with matching in vivo measured pressure ranges. Subsequently, the vessels were tested axially at the mean pulmonary arterial pressure by stretching them from in vivo plus 5% of their length. Parameter estimation showed that the LPA and RPA remodel at different rates: axially, both vessels decreased in Young's modulus at the early stage of the disease, and increased at the advanced disease stage. Circumferentially, the Young's modulus increased in advanced PAH, but it was only significant in the RPA. The damping properties also changed in PAH; in the LPA relaxation times decreased continuously as the disease progressed, while in the RPA they initially increased and then decreased. Our modeling efforts were corroborated by the restructuring organization of the fibers imaged under multiphoton microscopy, where the collagen fibers become strongly aligned to the 45 deg angle in the RPA from an uncrimped and randomly organized state. Additionally, collagen content increased almost 10% in the RPA from the placebo to advanced PAH.

ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension.

PubMed

Budas, Grant R; Boehm, Mario; Kojonazarov, Baktybek; Viswanathan, Gayathri; Tian, Xia; Veeroju, Swathi; Novoyatleva, Tatyana; Grimminger, Friedrich; Hinojosa-Kirschenbaum, Ford; Ghofrani, Hossein A; Weissmann, Norbert; Seeger, Werner; Liles, John T; Schermuly, Ralph T

2018-02-01

Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, and fibrosis. We investigated whether pharmacological inhibition of the redox-sensitive apical MAPK, ASK1 (apoptosis signal-regulating kinase 1), can halt the progression of pulmonary vascular and RV remodeling. A selective, orally available ASK1 inhibitor, GS-444217, was administered to two preclinical rat models of PAH (monocrotaline and Sugen/hypoxia), a murine model of RV pressure overload induced by pulmonary artery banding, and cellular models. Oral administration of GS-444217 dose dependently reduced pulmonary arterial pressure and reduced RV hypertrophy in PAH models. The therapeutic efficacy of GS-444217 was associated with reduced ASK1 phosphorylation, reduced muscularization of the pulmonary arteries, and reduced fibrotic gene expression in the RV. Importantly, efficacy was observed when GS-444217 was administered to animals with established disease and also directly reduced cardiac fibrosis and improved cardiac function in a model of isolated RV pressure overload. In cellular models, GS-444217 reduced phosphorylation of p38 and JNK (c-Jun N-terminal kinase) induced by adenoviral overexpression of ASK1 in rat cardiomyocytes and reduced activation/migration of primary mouse cardiac fibroblasts and human pulmonary adventitial fibroblasts derived from patients with PAH. ASK1 inhibition reduced pathological remodeling of the pulmonary vasculature and the right ventricle and halted progression of pulmonary hypertension in rodent models. These preclinical data inform the first description of a causal role of ASK1 in PAH disease pathogenesis.

Lung Cancer in Patients with Severe Idiopathic Pulmonary Fibrosis: Critical Aspects.

PubMed

Bargagli, Elena; Bonti, Viola; Ferrari, Katia; Rosi, Elisabetta; Bindi, Alessandra; Bartolucci, Maurizio; Chiara, Moroni; Voltolini, Luca

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease limited to the lung with an undefined etiopathogenesis and a very short life expectancy (less than 5 years). IPF susceptibility has been associated with several genetic and environmental risk factors and the prognosis is conditioned by comorbidities such as gastro-esophageal reflux, depression, venous thromboembolism, pulmonary hypertension and lung cancer. At 5 years follow-up, 15% of IPF patients develop lung cancer, which can significantly reduce their survival. Because diagnostic or therapeutic procedures such as surgical, radiation or pharmacological treatments may induce acute exacerbations and increase mortality, the management of lung cancer in IPF patients is a very difficult task. This study discusses advantages and disadvantages of lung cancer treatments in patients with severe IPF, highlighting several controversial aspects on this topic, including potential nintedanib treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The induction of nitric oxide-mediated relaxation of human isolated pulmonary arteries by PACAP

PubMed Central

Cardell, Lars Olaf; Hjert, Ola; Uddman, Rolf

1997-01-01

The effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea-pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor NG-monomethyl L-arginine (L-NMMA).PACAP and VIP induced concentration-dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (Imax,%) and the potency (pEC50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VIP were both more potent that acetylcholine (ACh).Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arginine restored the dilator response of the L-NMMA treated arteries.PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium-dependency) between the two peptides. PMID:9134222

Diesel exhaust inhalation exposure induces pulmonary arterial hypertension in mice.

PubMed

Liu, Jing; Ye, Xiaoqing; Ji, Dapeng; Zhou, Xiaofei; Qiu, Cong; Liu, Weiping; Yu, Luyang

2018-06-01

Diesel exhaust (DE) is one of the main sources of urban air pollution. An increasing number of evidence showed the association of air pollution with cardiovascular diseases. Pulmonary arterial hypertension (PAH) is one of the most disastrous vascular diseases, which results in right ventricular failure and death. However, the relationship of DE inhalation exposure with PAH is still unknown. In this study, male adult mice were exposed by inhalation to filtered ambient air (negative control), 10% O 2 hypoxia (PAH-phenotype positive control), 350 μg/m 3 particulate matter whole DE, or the combination of DE and hypoxic condition. DE inhalation induced PAH-phenotype accompanied with increased right ventricular systolic pressure (RVSP), right ventricle hypertrophy and pulmonary arterial thickening in a mouse model. DE exposure induced the proliferation of vascular smooth muscle cells (VSMCs) and apoptosis of endothelial cells in pulmonary artery. DE inhalation exposure induced an accumulation of CD45 +  lymphocytes and CD68 +  macrophages surrounding and infiltrating pulmonary arteriole. The levels of pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and IL-13 produced by T helper 17 (Th17) and Th2 cells were markedly elevated in lung tissues of mice after DE inhalation exposure. Our findings suggest DE exposure induces PAH by activating Th17-skewed and Th2-droved responses, stimulating VSMCs proliferation and inducing endothelial cell apoptosis by the production of multifunctional pro-inflammatory cytokines, especially IL-6 and TNF-α. Considering the adverse impact of air pollution on health care, it is imperative to understand air pollution-induced susceptibility of progressive cardiopulmonary disease, such as PAH, and also elucidate critical mechanistic pathways which mediate pulmonary artery vascular remodeling and may serve as targets for preventive measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF).

PubMed

Win, Thida; Screaton, Nicholas J; Porter, Joanna C; Ganeshan, Balaji; Maher, Toby M; Fraioli, Francesco; Endozo, Raymondo; Shortman, Robert I; Hurrell, Lynn; Holman, Beverley F; Thielemans, Kris; Rashidnasab, Alaleh; Hutton, Brian F; Lukey, Pauline T; Flynn, Aiden; Ell, Peter J; Groves, Ashley M

2018-05-01

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18 F-FDG-PET/ CT to predict mortality in IPF. A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18 F-FDG-PET/CT. The overall maximum pulmonary uptake of 18 F-FDG (SUV max ), the minimum pulmonary uptake or background lung activity (SUV min ), and target-to-background (SUV max / SUV min ) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan-Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18 F-FDG-PET measurements and GAP score for risk stratification in IPF patients. During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data ("PET modified GAP score") refined the ability to predict mortality. A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

PubMed

Zhang, Duan-Zhen; Zhu, Xian-Yang; Lv, Bei; Cui, Chun-Sheng; Han, Xiu-Min; Sheng, Xiao-Tang; Wang, Qi-Guang; Zhang, Po

2014-08-01

No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure. © 2014 American Heart Association, Inc.

Noninvasive Doppler Tissue Measurement of Pulmonary Artery Compliance in Children with Pulmonary Hypertension

PubMed Central

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

2007-01-01

Background 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). Methods Dynamic compliance (Cdyn) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. Cdyn was calculated as: [(Ds − Dd)/(Dd × Ps)] × 104; where Ds = systolic diameter, Dd = diastolic diameter, and Ps = 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. Cdyn was also measured in an additional 13 patients undergoing reactivity studies. Results Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, Cdyn calculated by CMM DTI agreed with Cdyn 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 Cdyn values than control subjects (P < .01). Cdyn values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress–strain behavior of these arteries. Reactivity in Cdyn agreed with reactivity measured using impedance techniques. Conclusion The Cdyn 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. PMID:16581479

Suture Embolism of the Left Superior Lobar Pulmonary Artery.

PubMed

Ahn, Janice Seulgy; Grise, Joy; DelTondo, Joseph A

2018-05-31

Endogenous pulmonary thromboemboli are a common cause of noncardiac sudden natural death. Embolism of exogenous material is a rare but potential finding in autopsies following surgeries, medical procedures, penetrating trauma, and nonparenteral drug abuse. This report describes the first case of a suture embolism of the left superior lobar pulmonary artery following complicated abdominal surgery. © 2018 American Academy of Forensic Sciences.

Breathing pattern and breathlessness in idiopathic pulmonary fibrosis: An observational study.

PubMed

Olukogbon, Kasope L; Thomas, Paul; Colasanti, Ricardo; Hope-Gill, Ben; Williams, Edgar Mark

2016-02-01

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive decline in lung function and increasing dyspnoea. The aim of this study was to investigate the relationship among IPF, pulmonary function, resting tidal breathing patterns and level of breathlessness. Thirty-one participants with IPF and 17 matched healthy controls underwent lung function testing, followed by a 2-min period of resting tidal breathing. The IPF cohort was stratified according to disease severity, based on their forced vital capacity and diffusion capacity for carbon monoxide. In comparison to the healthy controls, the IPF cohort showed a higher tidal volume, VT , of 0.22 L (P = 0.026) and a raised minute ventilation in the severest IPF group, while no differences in the timing of inspiration or expiration were observed. In the IPF cohort, the ratio of VT to forced vital capacity was around 15% higher. These changes corresponded with an increase in the self-reported sensation of breathlessness. Those with IPF increased their depth of breathing with worsening disease severity, with IPF-induced changes in pulmonary function and breathlessness associated with an altered tidal breathing pattern. © 2015 Asian Pacific Society of Respirology.

Peptide-micelle hybrids containing fasudil for targeted delivery to the pulmonary arteries and arterioles to treat pulmonary arterial hypertension.

PubMed

Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul

2014-11-01

This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2004-04-01

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

Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

PubMed

Kusko, Rebecca L; Brothers, John F; Tedrow, John; Pandit, Kusum; Huleihel, Luai; Perdomo, Catalina; Liu, Gang; Juan-Guardela, Brenda; Kass, Daniel; Zhang, Sherry; Lenburg, Marc; Martinez, Fernando; Quackenbush, John; Sciurba, Frank; Limper, Andrew; Geraci, Mark; Yang, Ivana; Schwartz, David A; Beane, Jennifer; Spira, Avrum; Kaminski, Naftali

2016-10-15

Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

PubMed

Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

2015-12-01

Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension in children

PubMed Central

Al Dabbagh, Maha; Banjar, Hanna; Galal, Nasser; Kouatli, Amjad; Kandil, Hammam; Chehab, May

2014-01-01

Pulmonary hypertension (PH) is relatively uncommon in children. Pulmonary arterial hypertension (PAH) in pediatric comprises a wide spectrum of diseases, from a transient neonatal condition to a progressive disease associated with morbidity and mortality. Most common PAH in pediatric are idiopathic (IPAH) or PAH associated with congenital heart disease (PAH-CHD), while other associated conditions, such as connective tissue disease (CTD), are less common in pediatrics. Despite better understanding of PH and the availability of new medications during recent decades; the diagnosis, investigation and choice of therapy remain a challenge in children, as evidence-based recommendations depend mainly on adult studies. In this review, we provide a detailed discussion about the distinctive features of PAH in pediatric, mainly emphacysing on classification and diagnostic algorithm. PMID:25076989

Targeted Delivery of Pulmonary Arterial Endothelial Cells Overexpressing Interleukin-8 Receptors Attenuates Monocrotaline-Induced Pulmonary Vascular Remodeling

PubMed Central

Fu, Jinyan; Chen, Yiu-Fai; Zhao, Xiangmin; Creighton, Judy; Guo, Yuan-Yuan; Hage, Fadi G.; Oparil, Suzanne; Xing, Daisy D.

2014-01-01

Objective Interleukin-8 (IL8) receptors IL8RA and IL8RB (ILRA/B) on neutrophil membranes bind to IL8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and/or inflammation. This study tested the hypothesis that administration of rat pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the adhesion of ECs to the injured lung and inhibit monocrotaline (MCT)-induced pulmonary inflammation, arterial thickening and hypertension, and right ventricular (RV) hypertrophy. Approach and Results The treatment groups included 10-wk-old ovariectomized Sprague-Dawley rats that received s.c. injection of phosphate-buffered-saline (Vehicle); a single injection of MCT (MCT alone, 60 mg/kg, s.c.); MCT followed by i.v. transfusion of ECs transduced with the empty adenoviral vector (Null-EC); and MCT followed by i.v. transfusion of ECs overexpressing IL8RA/B (IL8RA/B-EC, 1.5×106 cells/rat). Two days or 4 wks after MCT treatment, eNOS, iNOS, CINC-2β (IL8 equivalent in rat) and MCP-1 expression; neutrophil and macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology were measured by histological and immunohistochemical techniques. Pro-inflammatory cytokine/chemokine protein levels were measured by Multiplexed rat specific magnetic beads based sandwich immunoassay in total lung homogenates. Transfusion of IL8RA/B-ECs significantly reduced MCT-induced neutrophil infiltration and pro-inflammatory mediator (IL-8, MCP-1, iNOS, CINC and MIP-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary artery pressure, and pulmonary arteriole and RV hypertrophy and remodeling. Conclusion These provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature. PMID:24790141

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

PubMed

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.

VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats

PubMed Central

Farkas, Laszlo; Farkas, Daniela; Ask, Kjetil; Möller, Antje; Gauldie, Jack; Margetts, Peter; Inman, Mark; Kolb, Martin

2009-01-01

Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary pulmonary hypertension (PH) and ultimately death. Despite this known association, the precise mechanism of disease remains unknown. Using a rat model of IPF, we explored the role of the proangiogenic and antiapoptotic growth factor VEGF in the vascular remodeling that underlies PH. In this model, adenoviral delivery of active TGF-β1 induces pulmonary arterial remodeling, loss of the microvasculature in fibrotic areas, and increased pulmonary arterial pressure (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF and its receptor, which were inversely correlated with PAP and endothelial cell apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased vascularization, and improved PAP due to reduced remodeling but worsened PF. These data show that experimental pulmonary fibrosis (PF) leads to loss of the microvasculature through increased apoptosis and to remodeling of the pulmonary arteries, with both processes resulting in PH. As administration of VEGF ameliorated the PH in this model but concomitantly aggravated the fibrogenic process, VEGF-based therapies should be used with caution. PMID:19381013

Tricuspid regurgitation progression and regression in pulmonary arterial hypertension: implications for right ventricular and tricuspid valve apparatus geometry and patients outcome.

PubMed

Medvedofsky, Diego; Aronson, Doron; Gomberg-Maitland, Mardi; Thomeas, Vasiliki; Rich, Stuart; Spencer, Kirk; Mor-Avi, Victor; Addetia, Karima; Lang, Roberto M; Shiran, Avinoam

2017-01-01

The aim of this study was to determine the mechanism of tricuspid regurgitation (TR) progression in pulmonary arterial hypertension (PAH) and its effect on survival. We studied 88 patients with PAH and functional TR (mean pulmonary artery pressure 49 ± 14 mmHg; 43% idiopathic PAH) who had serial echocardiograms. TR progression (n = 35) was defined as ≤mild TR on Echo 1 and ≥moderate TR on Echo 2. TR regression (n = 17) was defined as ≥moderate TR on Echo 1 and ≤mild TR on Echo 2. Stable TR (n = 36) was defined as ≤mild TR on both echoes. TR progression was associated with an increase in pulmonary artery systolic pressure (PASP, 62 ± 22-92 ± 23 mmHg, P < 0.0001), right ventricular (RV) enlargement, mainly at mid-ventricular level, increased RV sphericity (6.1 ± 1.7-6.9 ± 1.8, P = 0.004), tricuspid annular (TA) dilatation (4.0 ± 0.7-4.6 ± 0.7 cm, P < 0.0001), and increased tricuspid valve (TV) tenting area (2.0 ± 0.7-2.5 ± 1.0 cm 2 , P = 0.0003). TR regression was associated with a reduction in PASP (84 ± 15-55 ± 18 mmHg, P < 0.0001), reverse RV remodelling with a reduction in RV sphericity (6.3 ± 1.4-5.5 ± 1.0, P = 0.02), and a reduction in TA size (4.1 ± 0.7-3.6 ± 0.7 cm, P = 0.02) and TV tenting (2.1 ± 0.7-1.3 ± 0.5 cm 2 , P = 0.0002). TR progression was associated with all-cause mortality (log-rank P = 0.0007). In PAH, TR progression was associated with worsening pulmonary hypertension and adverse RV and TV apparatus remodelling. TR progression is associated with poor outcome in PAH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Venous Fragment Embolism to the Pulmonary Artery: A Rare Occurrence - Case Report and Literature Review of Venous Fragment Embolization to the Pulmonary Artery

DTIC Science & Technology

2009-09-01

identified the high density (3000 Hounsfield Units ) intravascular pulmonary fragment in the same location, right lower lobe pulmonary artery, measuring...debridement and a four- compartment fasciotomy due to increasing compartment pressures. Anticoagulation was continued, 4 units of blood Report...NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Uniformed

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

PubMed

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

2016-05-01

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

Assessing idiopathic pulmonary fibrosis (IPF) with bronchoscopic OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hariri, Lida P.; Adams, David C.; Colby, Thomas V.; Tager, Andrew M.; Suter, Melissa J.

2016-03-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal form of fibrotic lung disease, with a significantly worse prognosis than other forms of pulmonary fibrosis (3-year survival rate of 50%). Distinguishing IPF from other fibrotic diseases is essential to patient care because it stratifies prognosis and therapeutic decision-making. However, making the diagnosis often requires invasive, high-risk surgical procedures to look for microscopic features not seen on chest CT, such as characteristic cystic honeycombing in the peripheral lung. Optical coherence tomography (OCT) provides rapid 3D visualization of large tissue volumes with microscopic resolutions well beyond the capabilities of CT. We aim to determine whether bronchoscopic OCT can provide a low-risk, non-surgical method for IPF diagnosis. We have developed bronchoscopic OCT catheters that access the peripheral lung and conducted in vivo peripheral lung imaging in patients, including those with pulmonary fibrosis. We also conducted bronchoscopic OCT in ex vivo lung from pulmonary fibrosis patients, including IPF, to determine if OCT could successfully visualize features of IPF through the peripheral airways. Our results demonstrate that OCT is able to visualize characteristic features of IPF through the airway, including microscopic honeycombing (< 1 mm diameter) not visible by CT, dense peripheral fibrosis, and spatial disease heterogeneity. We also found that OCT has potential to distinguish mimickers of IPF honeycombing, such as traction bronchiectasis and emphysema, from true honeycombing. These findings support the potential of bronchoscopic OCT as a minimally-invasive method for in vivo IPF diagnosis. However, future clinical studies are needed to validate these findings.

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis.

PubMed

Ley, Brett; Swigris, Jeffrey; Day, Bann-Mo; Stauffer, John L; Raimundo, Karina; Chou, Willis; Collard, Harold R

2017-09-15

Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up. In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the

Workshop on Idiopathic Pulmonary Fibrosis in Older Adults

PubMed Central

Castriotta, Richard J.; Eldadah, Basil A.; Foster, W. Michael; Halter, Jeffrey B.; Hazzard, William R.; Kiley, James P.; King, Talmadge E.; Horne, Frances McFarland; Nayfield, Susan G.; Reynolds, Herbert Y.; Schmader, Kenneth E.; Toews, Galen B.

2010-01-01

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary research, but these efforts have great potential to improve care for patients with IPF. PMID:20822991

Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

NASA Astrophysics Data System (ADS)

Waters, Kendall R.; Mukdadi, Osama M.

2005-04-01

Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

[Compression of trachea and esophagus by abnormal course of the left pulmonary artery (author's transl)].

PubMed

Lang, D; Hofstetter, R; Müssig, G; von Bernuth, G

1975-11-01

A three months old infant with abnormal origine and course of the left pulmonary artery is described. The course of the left pulmonary artery between oesophagus and trachea causes narrowing of the distal trachea leading to in- and expiratory stridor. A ventral indentation of the oesophagus, visible on the lateral plane of an oesophageal roentgenogram, is characteristic for the anomaly which can be proven by pulmonary angiography.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

PubMed

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev

2016-01-01

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

Occlusion pressure analysis role in partitioning of pulmonary vascular resistance in CTEPH.

PubMed

Toshner, Mark; Suntharalingam, Jay; Fesler, Pierre; Soon, Elaine; Sheares, Karen K; Jenkins, David; White, Paul; Morrell, Nicholas W; Naeije, Robert; Pepke-Zaba, Joanna

2012-09-01

Flow-directed pulmonary artery occlusion is posited to enable partitioning of vascular resistance into small and large vessels. As such it may have a role in assessment for pulmonary endarterectomy. To test if the occlusion technique distinguished small from large vessel disease we studied 59 subjects with chronic thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary arterial hypertension (IPAH), and connective tissue disease (CTD)-associated PAH. At right heart catheterisation, occlusion pressures were recorded. With fitting of the pressure decay curve, pulmonary vascular resistance was partitioned into downstream (small vessels) and upstream (large vessels, Rup). 47 patients completed the study; 14 operable CTEPH, 15 inoperable CTEPH, 13 idiopathic or CTD-PAH and five post-operative CTEPH. There was a significant difference in mean Rup in the proximal operable CTEPH group 87.3 (95% CI 84.1-90.5); inoperable CTEPH mean 75.8 (95% CI 66.76-84.73), p=0.048; and IPAH/CTD, mean 77.1 (95% CI 71.86-82.33), p=0.003. Receiver operating characteristic curves to distinguish operable from inoperable CTEPH demonstrated an area under the curve of 0.75, p=0.0001. A cut-off of 79.3 gave 100% sensitivity (95% CI 73.5-100%) but 57.1% specificity (95% CI 28.9-82.3%). In a subgroup analysis of multiple lobar sampling there was demonstrable heterogeneity. Rup is significantly increased in operable proximal CTEPH compared with non-operable distal CTEPH and IPAH/CTD-PAH. Rup variability in patients with CTEPH and PAH is suggestive of pathophysiological heterogeneity.

Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis: Validation Against Pulmonary Function.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Kokosi, Maria; Nair, Arjun; Karwoski, Ronald; Raghunath, Sushravya M; Walsh, Simon L F; Wells, Athol U; Hansell, David M

2016-09-01

The aim of the study was to determine whether a novel computed tomography (CT) postprocessing software technique (CALIPER) is superior to visual CT scoring as judged by functional correlations in idiopathic pulmonary fibrosis (IPF). A total of 283 consecutive patients with IPF had CT parenchymal patterns evaluated quantitatively with CALIPER and by visual scoring. These 2 techniques were evaluated against: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), and a composite physiological index (CPI), with regard to extent of interstitial lung disease (ILD), extent of emphysema, and pulmonary vascular abnormalities. CALIPER-derived estimates of ILD extent demonstrated stronger univariate correlations than visual scores for most pulmonary function tests (PFTs): (FEV1: CALIPER R=0.29, visual R=0.18; FVC: CALIPER R=0.41, visual R=0.27; DLco: CALIPER R=0.31, visual R=0.35; CPI: CALIPER R=0.48, visual R=0.44). Correlations between CT measures of emphysema extent and PFTs were weak and did not differ significantly between CALIPER and visual scoring. Intriguingly, the pulmonary vessel volume provided similar correlations to total ILD extent scored by CALIPER for FVC, DLco, and CPI (FVC: R=0.45; DLco: R=0.34; CPI: R=0.53). CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration.

Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

PubMed

Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

2012-01-01

It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity < 60%) who underwent surgical treatment between January 2002 and April 2010. A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included. The average age of the patients was 16.53 years (ranged 10 - 44). The demographic distribution, medical records, and radiographs of all patients were collected. All patients received arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6

Systemic Artery to Pulmonary Artery Fistula Associated with Mitral Regurgitation: Successful Treatment with Endovascular Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwazawa, Jin, E-mail: iwazawa.jin@nissay-hp.or.j; Nakamura, Kenji; Hamuro, Masao

We present the case of a 60-year-old woman with symptomatic mitral regurgitation caused by a left-to-right shunt via anastomoses consisting of microfistulae, most likely of inflammatory origin, between the right subclavian artery and the right pulmonary artery. The three arteries responsible for fistulous formation, including the internal mammary, thyrocervical, and lateral thoracic arteries, were successfully occluded by transcatheter embolization using superabsorbent polymer microsphere (SAP-MS) particles combined with metallic coils. No complications have been identified following treatment with SAP-MS particles. This approach significantly reduced the patient's mitral regurgitation and she has remained asymptomatic for more than 4 years.

Impact of Chronic Hypoxia on Proximal Pulmonary Artery Wave Propagation and Mechanical Properties in Rats.

PubMed

Su, Junjing; Logan, Charmilie C; Hughes, Alun D; Parker, Kim H; Dhutia, Niti M; Danielsen, Carl Christian; Simonsen, Ulf

2018-03-16

Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals in each group), the animals underwent transthoracic echocardiography and pulmonary artery catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis (WIA) was performed. Artery rings obtained from the pulmonary trunk, right and left PAs and the aorta were subjected to a tensile test to rupture. Collagen and elastin content was determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus and wall viscosity increased; while the elastin:collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in the hypoxic and normoxic animals with negligible wave reflection. In contrast, aortic maximal elastic modulus remained unchanged, while the wall viscosity decreased. There was no evidence of altered arterial wave propagation in the proximal PAs of hypoxic rats, while the extracellular matrix protein composition altered and the collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.

[Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a complication of Lecompte maneuver for tetralogy of Fallot associated with absent pulmonary valve].

PubMed

Honda, Yoshihiro; Suzuki, Shoji; Kaga, Shigeaki; Yoshida, Yukiyo; Kimura, Mitsuhiro; Kamiya, Kentaro; Sakakibara, Kenji; Katsu, Masatake

2015-05-01

The patient was diagnosed with tetralogy of Fallot associated with absent pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from respiratory distress on day 14 and received non-invasive positive pressure ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair including right ventricular outflow repair with a monocusp patch, patch closure of the ventricular septum defect and right pulmonary transposition to the anterior of the ascending aorta following the Lecompte maneuver for airway decompression. He was subsequently discharged to home and exhibited an uneventful clinical course with non-invasive positive pressure ventilation for 5 months postoperatively. However, right pulmonary artery and supra-aortic stenosis was noted 2 years after the operation. Computed tomography (CT) and angiography showed ascending aorta strangulation by the right pulmonary artery with right ventricular outflow regurgitation. Right pulmonary artery reconstruction using polytetrafluoroethylene graft interposition and repeat right ventricular outflow repair with bicuspid hand-sewn valves was therefore performed;the postoperative course was uneventful. Pre- and post-operative management using non-invasive positive pressure ventilation and airway decompression with pulmonary artery translocation is a useful strategy in patients exhibiting symptomatic tetralogy of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

Recent advances in understanding idiopathic pulmonary fibrosis

PubMed Central

Daccord, Cécile; Maher, Toby M.

2016-01-01

Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645

Determination of lung segments in computed tomography images using the Euclidean distance to the pulmonary artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoecker, Christina; Moltz, Jan H.; Lassen, Bianca

Purpose: Computed tomography (CT) imaging is the modality of choice for lung cancer diagnostics. With the increasing number of lung interventions on sublobar level in recent years, determining and visualizing pulmonary segments in CT images and, in oncological cases, reliable segment-related information about the location of tumors has become increasingly desirable. Computer-assisted identification of lung segments in CT images is subject of this work.Methods: The authors present a new interactive approach for the segmentation of lung segments that uses the Euclidean distance of each point in the lung to the segmental branches of the pulmonary artery. The aim is tomore » analyze the potential of the method. Detailed manual pulmonary artery segmentations are used to achieve the best possible segment approximation results. A detailed description of the method and its evaluation on 11 CT scans from clinical routine are given.Results: An accuracy of 2–3 mm is measured for the segment boundaries computed by the pulmonary artery-based method. On average, maximum deviations of 8 mm are observed. 135 intersegmental pulmonary veins detected in the 11 test CT scans serve as reference data. Furthermore, a comparison of the presented pulmonary artery-based approach to a similar approach that uses the Euclidean distance to the segmental branches of the bronchial tree is presented. It shows a significantly higher accuracy for the pulmonary artery-based approach in lung regions at least 30 mm distal to the lung hilum.Conclusions: A pulmonary artery-based determination of lung segments in CT images is promising. In the tests, the pulmonary artery-based determination has been shown to be superior to the bronchial tree-based determination. The suitability of the segment approximation method for application in the planning of segment resections in clinical practice has already been verified in experimental cases. However, automation of the method accompanied by an evaluation on a

Proinflammatory high-density lipoprotein results from oxidized lipid mediators in the pathogenesis of both idiopathic and associated types of pulmonary arterial hypertension

PubMed Central

Hough, Greg; Hama, Susan; Aboulhosn, Jamil; Belperio, John A.; Saggar, Rajan; Van Lenten, Brian J.; Ardehali, Abbas; Eghbali, Mansoureh; Reddy, Srinivasa; Fogelman, Alan M.; Navab, Mohamad

2015-01-01

Abstract Pulmonary arterial hypertension (PAH) is characterized by abnormal elaboration of vasoactive peptides, endothelial cell dysfunction, vascular remodeling, and inflammation, which collectively contribute to its pathogenesis. We investigated the potential for high-density lipoprotein (HDL) dysfunction (i.e., proinflammatory effects) and abnormal plasma eicosanoid levels to contribute to the pathobiology of PAH and assessed ex vivo the effect of treatment with apolipoprotein A-I mimetic peptide 4F on the observed HDL dysfunction. We determined the “inflammatory indices” HII and LII for HDL and low-density lipoprotein (LDL), respectively, in subjects with idiopathic PAH (IPAH) and associated PAH (APAH) by an in vitro monocyte chemotaxis assay. The 4F was added ex vivo, and repeat LII and HII values were obtained versus a sham treatment. We further determined eicosanoid levels in plasma and HDL fractions from patients with IPAH and APAH relative to controls. The LIIs were significantly higher for IPAH and APAH patients than for controls. Incubation of plasma with 4F before isolation of LDL and HDL significantly reduced the LII values, compared with sham-treated LDL, for IPAH and APAH. The increased LII values reflected increased states of LDL oxidation and thereby increased proinflammatory effects in both cohorts. The HIIs for both PAH cohorts reflected a “dysfunctional HDL phenotype,” that is, proinflammatory HDL effects. In contrast to “normal HDL function,” the determined HIIs were significantly increased for the IPAH and APAH cohorts. Ex vivo 4F treatment significantly improved the HDL function versus the sham treatment. Although there was a significant “salutary effect” of 4F treatment, this did not entirely normalize the HII. Significantly increased levels for both IPAH and APAH versus controls were evident for the eicosanoids 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE, while no statistical differences were evident for comparisons of

Liposomal Fasudil, a Rho-Kinase Inhibitor, for Prolonged Pulmonary Preferential Vasodilation in Pulmonary Arterial Hypertension

PubMed Central

Gupta, Vivek; Gupta, Nilesh; Shaik, Imam H.; Mehvar, Reza; McMurtry, Ivan F.; Oka, Masahiko; Nozik-Grayck, Eva; Komatsu, Masanobu; Ahsan, Fakhrul

2013-01-01

Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were then characterized for various physicochemical properties. Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH. The entrapment efficiency of optimized liposomal fasudil formulations was between 68.1±0.8% and 73.6±2.3%, and the cumulative release at 37°C was 98–99% over a period of 5 days. Compared to intravenous (IV) fasudil, a ~10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols. The t1/2 of IV fasudil was 0.39±0.12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4.71±0.72 h. One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37.6±5.7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats. Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH. PMID:23353807

Computational Fluid Dynamics Modeling of the Human Pulmonary Arteries with Experimental Validation.

PubMed

Bordones, Alifer D; Leroux, Matthew; Kheyfets, Vitaly O; Wu, Yu-An; Chen, Chia-Yuan; Finol, Ender A

2018-05-21

Pulmonary hypertension (PH) is a chronic progressive disease characterized by elevated pulmonary arterial pressure, caused by an increase in pulmonary arterial impedance. Computational fluid dynamics (CFD) can be used to identify metrics representative of the stage of PH disease. However, experimental validation of CFD models is often not pursued due to the geometric complexity of the model or uncertainties in the reproduction of the required flow conditions. The goal of this work is to validate experimentally a CFD model of a pulmonary artery phantom using a particle image velocimetry (PIV) technique. Rapid prototyping was used for the construction of the patient-specific pulmonary geometry, derived from chest computed tomography angiography images. CFD simulations were performed with the pulmonary model with a Reynolds number matching those of the experiments. Flow rates, the velocity field, and shear stress distributions obtained with the CFD simulations were compared to their counterparts from the PIV flow visualization experiments. Computationally predicted flow rates were within 1% of the experimental measurements for three of the four branches of the CFD model. The mean velocities in four transversal planes of study were within 5.9 to 13.1% of the experimental mean velocities. Shear stresses were qualitatively similar between the two methods with some discrepancies in the regions of high velocity gradients. The fluid flow differences between the CFD model and the PIV phantom are attributed to experimental inaccuracies and the relative compliance of the phantom. This comparative analysis yielded valuable information on the accuracy of CFD predicted hemodynamics in pulmonary circulation models.

Experimental pulmonary embolism: effects of the thrombus and attenuation of pulmonary artery injury by low-molecular-weight heparin.

PubMed

Rectenwald, John E; Deatrick, K Barry; Sukheepod, Pasu; Lynch, Erin M; Moore, Andrea J; Moaveni, Daria M; Dewyer, Nicholas A; Deywer, Nicholas A; Luke, Catherine E; Upchurch, Gilbert R; Wakefield, Thomas W; Kunkel, Steven L; Henke, Peter K

2006-04-01

Pulmonary embolism (PE) is a life-threatening condition that is associated with the long-term sequelae of chronic pulmonary hypertension. Prior experimental work has suggested that post-PE inflammation is accompanied by pulmonary artery intimal hyperplasia. This study evaluated the effect of the thrombus and tested the hypothesis that thrombolytic, antiplatelet, and anticoagulant agents would decrease pulmonary injury. Male Sprague-Dawley rats (n = 267) underwent laparotomy and temporary clip occlusion of the infrarenal inferior vena cava for the formation of endogenous thrombus or placement of an inert silicone "thrombus." Two days later, repeat laparotomy was performed, the clip removed, and the thrombus or silicone plug was embolized to the lungs. The endogenous thrombus group received normal saline, low-molecular-weight heparin (LMWH), tissue plasminogen activator (tPA), or a gIIB/IIIA antagonist (abciximab). Lung tissue was harvested at various times over 21 days and assayed for total collagen, monocyte chemoattractant protein-1 (MCP-1), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-beta). Fixed sections were stained with trichrome for intimal hyperplasia determination and ED-1 monocytes and alpha-actin-positive staining. The overall survival for rats undergoing PE was 90%, was not affected by treatment, and 84% of all PE localized to the right pulmonary artery. The PE significantly reduced Pa(O2) in all groups. Compared with controls, the silicone emboli group had an increased level of IL-13 on day 1, an increased level of MCP-1 on day 4, and an increase in the levels of all inflammatory mediators on day 14 (P < .05). Accompanying these differences were greater pulmonary artery intimal hyperplasia at days 4 and 21 in the silicone group compared with controls (P < .05). LMWH treatment in the thrombus of PE rats significantly decreased IL-13 levels at all time points, whereas treatment with abciximab or tPA significantly increased IL-13

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

PubMed

Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

2018-06-01

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy

PubMed Central

Caminati, Antonella; Conti, Sara; Cesana, Giancarlo

2016-01-01

Background Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005–2010. Methods For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD). IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000–2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5-year washout period. Results The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males. Conclusions The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved. PMID:26841042

Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy.

PubMed

Harari, Sergio; Madotto, Fabiana; Caminati, Antonella; Conti, Sara; Cesana, Giancarlo

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005-2010. For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD). IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000-2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5-year washout period. The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males. The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved.

ITE inhibits growth of human pulmonary artery endothelial cells.

PubMed

Pang, Ling-Pin; Li, Yan; Zou, Qing-Yun; Zhou, Chi; Lei, Wei; Zheng, Jing; Huang, Shi-An

2017-10-01

Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.

The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

PubMed

Neumann, Vanessa; Knies, Ralf; Seidinger, Alexander; Simon, Annika; Lorenz, Kristina; Matthey, Michaela; Breuer, Johannes; Wenzel, Daniela

2018-05-01

Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

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

PubMed

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

2010-03-31

Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-beta1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-beta1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-beta1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.

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.

PubMed

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.

Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

PubMed

Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

2016-02-01

Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

Anomalous origin of circumflex coronary artery from right pulmonary artery in a hypoplastic left heart syndrome child

PubMed Central

Kansy, Andrzej; Łaniewski-Wołłk, Przemysław

2014-01-01

We describe the case of a newborn with hypoplastic left heart syndrome (HLHS) and aberrant origin of the circumflex coronary artery from the right pulmonary artery. The patient underwent a modified Norwood procedure with direct reimplantation of the circumflex coronary artery to the neo-aorta, but died on the 5th postoperative day because of myocardial failure. Detailed assessment of coronary arteries as part of the routine echocardiographic evaluation of HLHS and intraoperative inspection of them is crucial. PMID:26336423

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.

PubMed

Ji, Ying-qun; Feng, Min; Zhang, Zhong-he; Lu, Wei-xuan; Wang, Chen

2013-01-01

The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE. Rats were allocated to the VTE (n = 54) or control groups (n = 9). The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT). One, four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE). The rats were sacrificed 1, 4 or 7 days later (D(n(1,4,7)) P(n(1,4,7)) subgroups (n = 6)), and the lungs were examined using light and electron microscopy. On gross dissection, the rate of DVT formation was higher on day 1 (D(1)P(n): 100%, 18/18) than day 4 (D(4)P(n): 83%, 15/18; χ(2) = 5.900, P = 0.015) or day 7 (D(7)P(n): 44%, 8/18; χ(2) = 13.846, P = 0.000). On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D(1)P(n) subgroup (39%, 7/18) than the D(4)P(n) (73%, 11/15; χ(2) = 3.915, P = 0.048) and D(7)P(n) subgroups (100%, 8/8; χ(2) = 8.474, P = 0.004); however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi. This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

PubMed

Sun, Tong; Liu, Jing; Zhao, De Wei

2016-05-01

There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis.Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1.Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to -0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02-0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: -0.13-0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: -0.06-0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19-106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3-5.12; P = 0.28) between the N-acetylcysteine group and the control group.N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes in forced vital capacity

[Impact of multi-layer spiral CT angiography of bronchial artery and pulmonary artery in assessment of the main blood supply to the primary lung cancer].

PubMed

Xiao, Xiang-sheng; Yu, Hong; Li, Hui-min; Liu, Shi-yuan; Li, Cheng-zhou; Liu, Jing

2006-04-01

To investigate the blood supply of primary lung cancer (PLC) using CT angiography for bronchial artery (BA) and pulmonary artery (PA). Thin-section enhanced multi-layer spiral CT (MSCT) were carried out in 147 primary lung cancer patients and 46 healthy subjects as control. Three-dimensional images of bronchial artery and pulmonary artery were obtained using volume render (VR) and multi-planar reconstruction (MPR) or maximum intensity projection (MIP) at the workstation, and their morphological findings and relationship with the mass were assessed. 136 primary lung cancer patients and 32 healthy controls were evaluated for at least one bronchial artery displayed clearly in VR. The detective rate of the bronchial artery was 92.5% and 69.6%, respectively. The bronchial artery caliber and the total section area of lesion side in lung cancer patients were significantly larger than that on the contralateral side and that of the control (P < 0.05). Bronchial artery on the lesion side in lung cancer was dilated and tortuous, directly penetrating into the mass with reticularly anastomosed branches. In the PLC patients, all PA were shown clearly with normal morphological image though crossing over the masses in 54 patients; In 25 PLC patients, the PA being essentially intact, was pushed around and surrounded the mass, giving the "hold ball" sign; In 40 other PLC patients, PA being also intact, the mass surrounded and buried the PA from the outside, crushing the PA flat resulting in an eccentric or centrifugal shrinkage, forming the "dead branch" sign; In the rest 28 patients, the PA was surrounded and even compressed, forming the "residual root" sign. Primary lung cancer patient shows dilated bronchial arteries and increased bronchial artery blood flow, whereas pulmonary arteries just pass through the mass or are compressed by the mass. It is further demonstrated that the bronchial artery, instead of the pulmonary artery, is the main vessel of blood supply to the primary

Development of a technique for determination of pulmonary artery pulse wave velocity in horses.

PubMed

Silva, Gonçalo Teixeira de Almeida; Guest, Bruce B; Gomez, Diego E; McGregor, Martine; Viel, Laurent; O'Sullivan, M Lynne; Runciman, John; Arroyo, Luis G

2017-05-01

Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the main PA of 10 sedated horses. The pressure waves were used to determine PWV along the PA, using the statistical phase offset method. Histological analysis of the PA was performed to investigate the presence of fibro-calcified lesions. The mean (±SD) PWV was 2.3 ± 0.7 m/s in the proximal PA trunk and 1.1 ± 0.1 m/s further distal (15 cm) in a main PA branch. The mean (±SD) of mean arterial pressures in the proximal PA trunk was 30.1 ± 5.2 mmHg, and 22.0 ± 6.0 mmHg further distal (15 cm) within the main PA branch. The mean (±SD) pulse pressure in the proximal PA trunk was 15.0 ± 4.7 mmHg, and 13.5 ± 3.3 mmHg further distal (15 cm) within the main PA branch. Moderate to severe lesions of the tunica media of the PAs were observed in seven horses, but a correlation with PWV could not be established yet. Pulmonary artery PWV may be determined in standing horses. The technique described may allow further investigation of the effect of calcification of large PAs in the pathogenesis of equine pulmonary circulatory disorders. NEW & NOTEWORTHY Pulmonary artery pulse wave velocity was determined safely in standing sedated horses. The technique described may allow further investigation of the effect of calcification of large pulmonary arteries in the pathogenesis of pulmonary circulatory disorders in horses. Copyright © 2017 the American Physiological Society.

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

PubMed Central

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

Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

PubMed

Freitas, E R F S; Soares, B G O; Cardoso, J R; Atallah, A N

2007-07-18

Following coronary artery bypass graft (CABG), the main causes of postoperative morbidity and mortality are postoperative pulmonary complications, respiratory dysfunction and arterial hypoxemia. Incentive spirometry is a treatment technique that uses a mechanical device (an incentive spirometer) to reduce such pulmonary complications during postoperative care. To assess the effects of incentive spirometry for preventing postoperative pulmonary complications in adults undergoing CABG. We searched CENTRAL on The Cochrane Library (Issue 2, 2004), MEDLINE (1966 to December 2004), EMBASE (1980 to December 2004), LILACS (1982 to December 2004), the Physiotherapy Evidence Database (PEDro) (1980 to December 2004), Allied & Complementary Medicine (AMED) (1985 to December 2004), CINAHL (1982 to December 2004), and the Database of Abstracts of Reviews of Effects (DARE) (1994 to December 2004). References were checked and authors contacted. No language restrictions were applied. Randomized controlled trials comparing incentive spirometry with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. Two reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Reviewers' Handbook and extracted data from included trials. Four trials with 443 participants contributed to this review. There was no significant difference in pulmonary complications (atelectasis and pneumonia) between treatment with incentive spirometry and treatment with positive pressure breathing techniques (continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB)) or preoperative patient education. Patients treated with incentive spirometry had worse pulmonary function and arterial oxygenation compared with positive pressure breathing (CPAP, BiPAP, IPPB). Individual small trials suggest that there is no evidence of benefit from incentive

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

PubMed Central