Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

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Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

2006-01-01

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 by 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

Development of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT®) questionnaire: a new patient-reported outcome instrument for PAH.

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McCollister, Deborah; Shaffer, Shannon; Badesch, David B; Filusch, Arthur; Hunsche, Elke; Schüler, René; Wiklund, Ingela; Peacock, Andrew

2016-06-14

Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance. A cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18-80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments. Focus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social

An issue of literacy on pediatric arterial hypertension

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Teodoro, M. Filomena; Romana, Andreia; Simão, Carla

2017-11-01

Arterial hypertension in pediatric age is a public health problem, whose prevalence has increased significantly over time. Pediatric arterial hypertension (PAH) is under-diagnosed in most cases, a highly prevalent disease, appears without notice with multiple consequences on the children's health and future adults. Children caregivers and close family must know the PAH existence, the negative consequences associated with it, the risk factors and, finally, must do prevention. In [12, 13] can be found a statistical data analysis using a simpler questionnaire introduced in [4] under the aim of a preliminary study about PAH caregivers acquaintance. A continuation of such analysis is detailed in [14]. An extension of such questionnaire was built and applied to a distinct population and it was filled online. The statistical approach is partially reproduced in the present work. Some statistical models were estimated using several approaches, namely multivariate analysis (factorial analysis), also adequate methods to analyze the kind of data in study.

Pericardial effusion in pulmonary arterial hypertension

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2013-01-01

Abstract Pulmonary arterial hypertension (PAH) is a serious condition that can lead to right heart failure and death. Pericardial effusion in PAH is associated with significant morbidity and mortality, and its pathogenesis is complex and poorly understood. There are few data on the prevalence of pericardial effusion in PAH, and more importantly, the management of pericardial effusion is controversial. Current literature abounds with case reports, case series, and retrospective studies that have limited value for assessing this association. Hence, we summarize the available evidence on this ominous association and identify areas for future research. PMID:24618534

The study of risk in pulmonary arterial hypertension

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Gerald Simonneau

2012-09-01

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

Effects of exercise training in patients with idiopathic pulmonary arterial hypertension

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

2009-01-01

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise

Depression in pulmonary arterial hypertension: An undertreated comorbidity

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Sameer Verma

2016-01-01

Full Text Available Pulmonary arterial hypertension (PAH is a debilitating condition leading to progressive decline in functional capacity. As a result, PAH can lead to psychological impairment that can impact the overall disease status. The medical community has developed several screening questionnaires in order to assess depression in their patients allowing physicians to be at the forefront of recognizing clinical depression. There is a suggestion that depression symptomatology is more prevalent in the PAH population. The aim of this article is to review the current thought process about diagnosis and management of depression in PAH patients.

SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

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N. A. Shostak

2016-01-01

Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

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N. A. Shostak

2009-01-01

Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

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Jeremy A Falk

2010-04-01

Full Text Available Jeremy A Falk, Kiran J Philip, Ernst R SchwarzCedars Sinai Women’s Guild Lung Institute, Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USAAbstract: Pulmonary hypertension (PH is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH. Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5 inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.Keywords: PDE-5 inhibition, pulmonary hypertension, tadalafil

Egg and banana sign of severe pulmonary arterial hypertension.

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Veean, Satyam; Nixon, William; Keshavamurthy, Jayanth

2018-01-01

The egg and banana sign can be seen on chest computed tomography (CT) in patients with severe pulmonary arterial hypertension (PAH). It is identified by the presence of the pulmonary artery (PA) lateral to the aortic arch with the aortic arch being described as the banana and the PA as the egg.

Saudi experience in the management of pulmonary arterial hypertension; the outcome of PAH therapy with the exclusion of chronic parenteral prostacyclin

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Majdy Idrees

2015-01-01

Full Text Available Aims: The purpose of this study is to present our center′s experience in managing patients with pulmonary arterial hypertension (PAH. The main objective is to describe patients′ management profile and treatment outcome. Methods: This study presents the results from a single pulmonary hypertension (PH specialized center in Saudi Arabia. Both incidence and prevalence cases are included. We have previously reported the clinical and physiological characteristics at the time of diagnosis for this cohort of patients. In this study, we describe the clinical management and the outcome of therapy in the same cohort, who were prospectively followed for a mean of 22 months. Results: A total of 107 patients were identified as having PAH. At the time of enrollment, 56.1% of patients were in modified New York Heart Association functional class (NYHA FC III and 16.8% were in IV. Phosphdiesterase-5 inhibitor was the most commonly used target therapy (82.2% followed by endothelin receptors antagonist (74.4%. Only five patients (4.7% were candidate to use calcium channel blockers. Seventy-nine patients (73.8 % received a combination nonparenteral target therapy. Thirty-one patients (28.9% died during the follow-up period. Modified NYHA FC III and IV patients, portopulmonary hypertension, heritable PAH, and PAH associated with connective tissue diseases had the highest mortality rate (P < 0.001. Conclusion: Our patients are detected at advanced stage of the disease, and thus the mortality is still unacceptably high. Advanced functional class at presentation and certain disease subgroups are associated with increased mortality.

Drug-induced pulmonary arterial hypertension: a recent outbreak

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Gérald Simonneau

2013-09-01

Full Text Available Pulmonary arterial hypertension (PAH is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH.

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

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

2018-05-01

. Furthermore, myocardial perfusion imaging was not observed in the normal subjects but in pulmonary arterial hypertension patients, especially severe pulmonary arterial hypertension subgroup, and showed potential diagnostic properties for pulmonary arterial hypertension. In conclusion, mean pulmonary arterial pressure levels are correlated with several right heart catheterization and echocardiography markers in pulmonary arterial hypertension patients; echocardiography and 99m Tc myocardial perfusion can be used to evaluate right ventricle performance in pulmonary arterial hypertension patients. Impact statement In this study, we analyzed the clinical parameters for evaluating RV function, including right ventricle catheterization (RHC), echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging (MPI) in normal Asian subjects and PAH patients ( n = 23 for each group). Our results demonstrated that six RHC indexes, four echocardiography indexes and MPI index were significantly altered in PAH patients and correlated with the levels of mean pulmonary arterial pressure. Importantly, we evaluated the diagnostic performance of MPI and found that MPI has a strong diagnostic accuracy in PAH patients. The findings from this study will be of interest to clinical investigators who make diagnosis and therapeutic strategies for PAH patients.

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

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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 (parteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reversible Pulmonary Arterial Hypertension Associated with Interferon-Beta Treatment for Multiple Sclerosis

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E Gibbons

2015-01-01

Full Text Available Interferon (IFN therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH, and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.

Pulmonary artery hypertension in childhood: The transforming growth factor-β superfamily-related genes

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Shi-Min Yuan

2018-04-01

Full Text Available Pulmonary artery hypertension (PAH is very rare in childhood, and it can be divided into heritable, idiopathic drug- and toxin-induced and other disease (connective tissue disease, human immunodeficiency virus infection, portal hypertension, congenital heart disease, or schistosomiasis-associated types. PAH could not be interpreted solely by pathophysiological theories. The impact of the transforming growth factor-β superfamily-related genes on the development of PAH in children remains to be clarified. Pertinent literature on the transforming growth factor-β superfamily-related genes in relation to PAH in children published after the year 2000 was reviewed and analyzed. Bone morphogenetic protein receptor type II gene mutation promotes cell division or prevents cell death, resulting in an overgrowth of cells in small arteries throughout the lungs. About 20% of individuals with a bone morphogenetic protein receptor type II gene mutation develop symptomatic PAH. In heritable PAH, bone morphogenetic protein receptor type II mutations may be absent; while mutations of other genes, such as type I receptor activin receptor-like kinase 1 and the type III receptor endoglin (both associated with hereditary hemorrhagic telangiectasia, caveolin-1 and KCNK3, the gene encoding potassium channel subfamily K, member 3, can be detected, instead. Gene mutations, environmental changes and acquired adjustment, etc. may explain the development of PAH. The researches on PAH rat model and familial PAH members may facilitate the elucidations of the mechanisms and further provide theories for prophylaxis and treatment of PAH. Key Words: bone morphogenetic proteins, mutation, pulmonary hypertension

Key articles and guidelines in the management of pulmonary arterial hypertension: 2011 update.

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Johnson, Samuel G; Kayser, Steven R; Attridge, Rebecca L; Duvall, Laura; Kiser, Tyree H; Moote, Rebecca; Reed, Brent N; Rodgers, Jo E; Erstad, Brian

2012-06-01

Pharmacotherapeutic approaches for the management of pulmonary arterial hypertension (PAH) have expanded greatly in the last 10 years. Pulmonary arterial hypertension is a relatively rare disease and is associated with myriad disease processes. The older term for PAH, primary PAH, has been changed to represent these differences and to distinguish it from postcapillary PAH associated with left-sided heart failure. Limitations in evaluating treatment approaches for PAH include its rarity, the small number of patients included in clinical trials, and issues regarding the use of placebo-controlled trials in a disease with such a high mortality rate if left untreated. Management options include the use of prostacyclin and prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase inhibitors, as well as traditional background therapy with diuretics, digoxin, calcium channel blockers, and warfarin. Numerous drugs are under investigation to evaluate their possible roles in management. Combination therapy is increasingly becoming a standard approach to therapy, with mounting literature to document effectiveness. Current or emerging roles for the pharmacist in the management of PAH largely involves ensuring access to drug therapy, facilitating specialty pharmacy dispensing, and providing patient counseling. Newer roles may include future drug development, optimized use of investigational drugs, and specialized disease management programs. This compilation includes a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of pulmonary arterial hypertension (PAH). Most of the cited works present the results of significant human clinical studies that have shaped the management of patients with PAH. Limited primary literature is available for some topics, so in addition, consensus documents prepared by expert panels are reviewed. This compilation may serve as a

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

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Leslie A. Blair

2016-10-01

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

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

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Edmund M T Lau

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

Selective improvement of pulmonary arterial hypertension with a dual ETA/ETB receptors antagonist in the apolipoprotein E-/- model of PAH and atherosclerosis.

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Renshall, Lewis; Arnold, Nadine; West, Laura; Braithwaite, Adam; Pickworth, Josephine; Walker, Rachel; Alfaidi, Mabruka; Chamberlain, Janet; Casbolt, Helen; Thompson, A A Roger; Holt, Cathy; Iglarz, Marc; Francis, Sheila; Lawrie, Allan

2018-01-01

Idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients who also have an increased risk of co-morbid atherosclerosis. Apolipoprotein E-deficient (ApoE -/- ) mice develop atherosclerosis with severe PAH when fed a high-fat diet (HFD) and have increased levels of endothelin (ET)-1. ET-1 receptor antagonists (ERAs) are used for the treatment of PAH but less is known about whether ERAs are beneficial in atherosclerosis. We therefore examined whether treatment of HFD-ApoE -/- mice with macitentan, a dual ET A /ET B receptor antagonist, would have any effect on both atherosclerosis and PAH. ApoE -/- mice were fed chow or HFD for eight weeks. After four weeks of HFD, mice were randomized to a four-week treatment of macitentan by food (30 mg/kg/day dual ET A /ET B antagonist), or placebo groups. Echocardiography and closed-chest right heart catheterization were used to determine PAH phenotype and serum samples were collected for cytokine analysis. Thoracic aortas were harvested to assess vascular reactivity using wire myography, and histological analyses were performed on the brachiocephalic artery and aortic root to assess atherosclerotic burden. Macitentan treatment of HFD-fed ApoE -/- mice was associated with a beneficial effect on the PAH phenotype and led to an increase in endothelial-dependent relaxation in thoracic aortae. Macitentan treatment was also associated with a significant reduction in interleukin 6 (IL-6) concentration but there was no significant effect on atherosclerotic burden. Dual blockade of ET A /ET B receptors improves endothelial function and improves experimental PAH but had no significant effect on atherosclerosis.

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

NARCIS (Netherlands)

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

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

A Focus on Macitentan in the Treatment of Pulmonary Arterial Hypertension.

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Bedan, Martin; Grimm, Daniela; Wehland, Markus; Simonsen, Ulf; Infanger, Manfred; Krüger, Marcus

2018-05-02

The approval of macitentan has increased the number of pharmacological treatments of pulmonary arterial hypertension (PAH). Here, we review the effect on PAH of macitentan compared to other endothelin receptor antagonists (ERAs). Drugs targeting the endothelin (ET) pathway include the selective ET A receptor antagonist ambrisentan, the ET A /ET B receptor antagonists bosentan and macitentan which were recently approved for PAH treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

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Jafri, Salema; Ormiston, Mark L

2017-12-01

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

Screening for pulmonary arterial hypertension in systemic sclerosis

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J-L. Vachiéry

2009-09-01

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

Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

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Rachel D. Torok MD

2017-05-01

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

Advanced pulmonary arterial hypertension: mechanical support and lung transplantation

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Sonja Bartolome

2017-12-01

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

Patent ductus arteriosus with persistent pulmonary artery hypertension after transcatheter closure.

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Feng, Jianqi; Kong, Xiangqing; Sheng, Yanhui; Yang, Rong

2016-01-01

To observe the change in pulmonary artery systolic pressure (PASP) of patients with persistent pulmonary arterial hypertension (PAH) after patent ductus arteriosus (PDA) occlusion. After occlusion of PDA in patients with PAH, some patients still tend to suffer from persistent PAH. A chest X-ray, an electrocardiogram, and an echocardiogram were performed on nine patients at 24 hours, 1 and 6 months, and 1 year serially. There was a significant fall ( P 0.05). During the follow up, there was a further fall in the PASP in five patients (No 1, 5, 6, 7, and 8). Four patients (No 2, 3, 4, and 8) showed the evidence of worsening PAH and were treated with sildenafil. Patient 2 died from acute right heart failure after a period of 11 months from the time of transcatheter closure, triggered by pulmonary infection. Some patients with borderline hemodynamic data with PDA and PAH can deteriorate or keep sustained PAH after PDA closure. The treatment of permanent closure to these patients must be cautious.

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

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Gautam V Ramani

2010-05-01

Full Text Available Gautam V Ramani, Myung H ParkUniversity of Maryland, Baltimore, MD, USAAbstract: Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH. The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. Keywords: sildenafil, pulmonary arterial hypertension, phosphodiesterase type 5 inhibitor

Effects of exercise training in patients with idiopathic pulmonary arterial hypertension

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

2009-01-01

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise 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 biopsi...

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

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Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Supervised exercise training in patients with pulmonary arterial hypertension - analyses of the effectiveness and safety].

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Saxer, S; Rhyner, M; Treder, U; Speich, R; van Gestel, A J R

2012-02-01

Both in today's scientific research and in clinical practice, there exists a need to address the uncertainty concerning the effectiveness and safety of cardiopulmonary exercise training (CPET) in patients with pulmonary arterial hypertension (PAH). It is commonly believed that CPET may be dangerous for patients with PAH, because increasing pressure on the pulmonary arteries may worsen right-sided heart failure. Recently, the first clinical trials on exercise training in patients with pulmonary hypertension reported promising results. Extension of the walking distance at the 6-minute walk test improved quality of life, endurance capacity and a reduction in symptoms were observed after CPET. Furthermore, CPET was well tolerated by the patients in five clinical trials. In conclusion, it may be postulated that CPET is an effective therapy in patients with PAH and was tendentially well tolerated by the patients.

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

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Antonio Lopes

2014-01-01

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

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

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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.

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

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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.

Signal transduction in the development of pulmonary arterial hypertension

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

2013-01-01

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

Perceptions of Received Information, Social Support, and Coping in Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension

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Bodil Ivarsson

2014-01-01

Full Text Available Patients with a life-limiting diagnosis of pulmonary arterial hypertension (PAH or chronic thromboembolic pulmonary hypertension (CTEPH need disease-specific information, ability to cope, and functioning social networks. This cohort study investigated the experiences of PAH and CTEPH patients who received information about their diagnosis, treatment, and management, in addition to coping and social support. Sixty-eight adult patients (mean ∓ SD, age 67 ∓ 14; 66% women were included. A total of 54% of the patients wanted more information. Patients received information mostly in areas concerning medical test procedures, the diagnosis, disease severity, possible disease causes, and how to manage their disease. Coping ability was significantly better in patients who were satisfied with the received information (P= 0.0045. The information given to PAH or CTEPH patients and their communication with healthcare professionals can be greatly improved. Gaps in information and misunderstandings can be avoided by working in cooperation with the patients, their relatives, and within the PAH team.

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

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Froelich, Jens J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: jens.froelich@klinikum-hef.de; Koenig, Helmut [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: helmut.koenig@siemens.com; Knaak, Lennard [Department of Medicine, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: froehlic@staff.uni-marburg.de; Krass, Stefan [MeVis Research, Universitaetsallee 29, 28359 Bremen (Germany)], E-mail: krass@mevis.de; Klose, Klaus J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: klose@med.uni-marburg.de

2008-09-15

Objectives: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. Materials and methods: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3 mm; pitch 2; increment 2 mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. Results: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r = .85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p < .005), PA volumes also were significantly increased (p < .05) among the groups. Conclusions: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension.

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

International Nuclear Information System (INIS)

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

2008-01-01

Objectives: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. Materials and methods: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3 mm; pitch 2; increment 2 mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. Results: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r = .85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p < .005), PA volumes also were significantly increased (p < .05) among the groups. Conclusions: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension

Cellular, pharmacological, and biophysical evaluation of explanted lungs from a patient with sickle cell disease and severe pulmonary arterial hypertension.

Science.gov (United States)

Rogers, Natasha M; Yao, Mingyi; Sembrat, John; George, M Patricia; Knupp, Heather; Ross, Mark; Sharifi-Sanjani, Maryam; Milosevic, Jadranka; St Croix, Claudette; Rajkumar, Revathi; Frid, Maria G; Hunter, Kendall S; Mazzaro, Luciano; Novelli, Enrico M; Stenmark, Kurt R; Gladwin, Mark T; Ahmad, Ferhaan; Champion, Hunter C; Isenberg, Jeffrey S

2013-12-01

Pulmonary hypertension is recognized as a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). We now report benchtop phenotyping from the explanted lungs of the first successful lung transplant in SCD. Pulmonary artery smooth muscle cells (PASMCs) cultured from the explanted lungs were analyzed for proliferate capacity, superoxide (O2 (•-)) production, and changes in key pulmonary arterial hypertension (PAH)-associated molecules and compared with non-PAH PASMCs. Upregulation of several pathologic processes persisted in culture in SCD lung PASMCs in spite of cell passage. SCD lung PASMCs showed growth factor- and serum-independent proliferation, upregulation of matrix genes, and increased O2 (•-) production compared with control cells. Histologic analysis of SCD-associated PAH arteries demonstrated increased and ectopically located extracellular matrix deposition and degradation of elastin fibers. Biomechanical analysis of these vessels confirmed increased arterial stiffening and loss of elasticity. Functional analysis of distal fifth-order pulmonary arteries from these lungs demonstrated increased vasoconstriction to an α1-adrenergic receptor agonist and concurrent loss of both endothelial-dependent and endothelial-independent vasodilation compared with normal pulmonary arteries. This is the first study to evaluate the molecular, cellular, functional, and mechanical changes in end-stage SCD-associated PAH.

Causes and circumstances of death in pulmonary arterial hypertension.

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Tonelli, Adriano R; Arelli, Vineesha; Minai, Omar A; Newman, Jennie; Bair, Nancy; Heresi, Gustavo A; Dweik, Raed A

2013-08-01

The causes and circumstances surrounding death are understudied in patients with pulmonary arterial hypertension (PAH). We sought to determine the specific reasons and characteristics surrounding the death of patients with PAH. All deaths of patients with pulmonary hypertension (PH) followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the PH team. A total of 84 patients with PAH (age 58 ± 14 yr; 73% females) who died between June 2008 and May 2012 were included. PH was determined to be the direct cause of death (right heart failure or sudden death) in 37 (44%) patients; PH contributed to but did not directly cause death in 37 (44%) patients; and the death was not related to PH in the remaining cases (n = 7; 8.3%). In three (3.6%) patients the final cause of death could not be adequately assessed. Most patients died in a healthcare environment and most received PH-specific therapies. In our cohort, 50% of all patients with PAH and 75.7% of those who died of right heart failure received parenteral prostanoid therapy. Less than half of patients had advanced healthcare directives. Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

Pulmonary arterial hypertension associated with congenital heart disease

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Michele D'Alto

2012-12-01

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

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

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

2017-07-01

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

Prognostic factors in pediatric pulmonary arterial hypertension : A systematic review and meta-analysis

NARCIS (Netherlands)

Ploegstra, Mark-Jan; Zijlstra, Willemijn M. H.; Douwes, Johannes M.; Hillege, Hans L.; Berger, Rolf M. F.

2015-01-01

BACKGROUND: Despite the introduction of targeted therapies in pediatric pulmonary arterial hypertension (PAH), prognosis remains poor. For the definition of treatment strategies and guidelines, there is a high need for an evidence-based recapitulation of prognostic factors. The aim of this study was

Mortality in pulmonary arterial hypertension due to congenital heart disease: Serial changes improve prognostication

NARCIS (Netherlands)

Schuijt, M.T.U.; Blok, I.M.; Zwinderman, A.H.; Riel, A. van; Schuuring, M.J.; Winter, R.J. de; Duijnhouwer, A.L.; Dijk, A.P.J. van; Mulder, B.J.; Bouma, B.J.

2017-01-01

BACKGROUND: Adult patients with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) suffer from high mortality. This underlines the importance of adequate risk stratification to guide treatment decisions. Several baseline parameters are associated with mortality, however, their

Mortality in pulmonary arterial hypertension due to congenital heart disease: Serial changes improve prognostication

NARCIS (Netherlands)

Schuijt, M. T. U.; Blok, I. M.; Zwinderman, A. H.; van Riel, A. C. M. J.; Schuuring, M. J.; de Winter, R. J.; Duijnhouwer, A. L.; van Dijk, A. P. J.; Mulder, B. J. M.; Bouma, B. J.

2017-01-01

Background: Adult patients with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) suffer from high mortality. This underlines the importance of adequate risk stratification to guide treatment decisions. Several baseline parameters are associated with mortality, however, their

Perioperative Management of Pregnant Women With Idiopathic Pulmonary Arterial Hypertension: An Observational Case Series Study From China.

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Zhang, Jinglan; Lu, Jiakai; Zhou, Xiaorui; Xu, Xuefeng; Ye, Qing; Ou, Qitan; Li, Yanna; Huang, Jiapeng

2018-03-07

The mortality of pregnant women with idiopathic pulmonary arterial hypertension (PAH) is very high. There are limited data on the management of idiopathic PAH during pregnancy. The authors aimed to examine systematically the characteristics of parturient women with idiopathic PAH, to explore the adverse effects of idiopathic PAH on pregnancy outcomes, and to report the multidisciplinary perioperative management strategy from the largest comprehensive cardiac hospital in China. Observational case series study. Tertiary referral acute care hospital in Beijing, China. The cases of 17 consecutive pregnant idiopathic PAH patients undergoing abortion or parturition at Anzhen Hospital were reviewed retrospectively. Preoperative characteristics, anesthesia method, intensive care management, PAH-specific therapy, and maternal and neonatal outcomes were analyzed in this case series study. Maternal and neonatal outcomes were the main measures. The mean ages of the 17 parturient women with idiopathic PAH were 28.3 ± 5.4 years, and the mean systolic pulmonary arterial pressure was 97.9 ± 18.6 mmHg. Fifteen patients (88.2%) received PAH-specific therapy before delivery, including sildenafil, iloprost, and treprostinil. All except 1 parturient received epidural anesthesia for surgery due to an emergency Caesarean section. Three patients experienced pulmonary hypertension crisis that necessitated conversion to general anesthesia. Ten parturients underwent Caesarean delivery at a median gestational age of 31 weeks. Three patients developed acute pulmonary hypertensive crisis intraoperatively. Two patients underwent cardiopulmonary resuscitation and extracorporeal membrane oxygenation support. The maternal mortality was 17.6% (3/17). Of the 10 delivered neonates, 9 (90.0%) survived. The maternal mortality of the idiopathic PAH parturient was high in this case series from China. The authors applied epidural anesthesia, early management with multidisciplinary approaches, PAH

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

NARCIS (Netherlands)

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

2014-01-01

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

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

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Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

2018-04-01

Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their

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

OpenAIRE

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

2015-01-01

BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). METHODS: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the pre...

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

OpenAIRE

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

2015-01-01

Background Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). Methods Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO i...

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

Directory of Open Access Journals (Sweden)

Prakash Chelladurai

2016-06-01

Full Text Available Pulmonary arterial hypertension (PAH is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date.

MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension.

Science.gov (United States)

Deng, Lin; Blanco, Francisco J; Stevens, Hannah; Lu, Ruifang; Caudrillier, Axelle; McBride, Martin; McClure, John D; Grant, Jenny; Thomas, Matthew; Frid, Maria; Stenmark, Kurt; White, Kevin; Seto, Anita G; Morrell, Nicholas W; Bradshaw, Angela C; MacLean, Margaret R; Baker, Andrew H

2015-10-23

The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. To elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH. We identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-β (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression. We observed that miR-143-3p is selectively upregulated compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary arterial endothelial cells, we demonstrated a paracrine promigratory and proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative polymerase chain reaction and in situ hybridization showed elevated expression of miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, whereas inhibition of miR-143-3p blocked experimental pulmonary hypertension. Taken together, these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology. © 2015 American Heart Association, Inc.

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

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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.

2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

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Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang

2014-01-01

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817

Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience

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Olivier Sitbon

2017-01-01

Full Text Available Epoprostenol was the first therapy to be approved for the treatment of pulmonary arterial hypertension (PAH. In the 20 years since the introduction of this prostacyclin analogue, the outlook for patients with PAH has improved, with survival rates now double those from the era before the development of disease-specific treatments. Today, there are a large amount of data on the clinical role of prostacyclin treatments and a body of evidence attesting the efficacy of epoprostenol in improving exercise capacity, key haemodynamic parameters and PAH symptoms, as well as in reducing mortality. The place of epoprostenol in the therapeutic management of PAH continues to evolve, with the development of new formulations and use in combination with other drug classes. In this review, we provide a historical perspective on the first 20 years of epoprostenol, a therapy that led to evidence-based study of PAH-specific treatments and the subsequent expansion of treatment options for PAH.

The Voice of the Heart: Vowel-Like Sound in Pulmonary Artery Hypertension

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Mohamed Elgendi

2018-04-01

Full Text Available Increased blood pressure in the pulmonary artery is referred to as pulmonary hypertension and often is linked to loud pulmonic valve closures. For the purpose of this paper, it was hypothesized that pulmonary circulation vibrations will create sounds similar to sounds created by vocal cords during speech and that subjects with pulmonary artery hypertension (PAH could have unique sound signatures across four auscultatory sites. Using a digital stethoscope, heart sounds were recorded at the cardiac apex, 2nd left intercostal space (2LICS, 2nd right intercostal space (2RICS, and 4th left intercostal space (4LICS undergoing simultaneous cardiac catheterization. From the collected heart sounds, relative power of the frequency band, energy of the sinusoid formants, and entropy were extracted. PAH subjects were differentiated by applying the linear discriminant analysis with leave-one-out cross-validation. The entropy of the first sinusoid formant decreased significantly in subjects with a mean pulmonary artery pressure (mPAp ≥ 25 mmHg versus subjects with a mPAp < 25 mmHg with a sensitivity of 84% and specificity of 88.57%, within a 10-s optimized window length for heart sounds recorded at the 2LICS. First sinusoid formant entropy reduction of heart sounds in PAH subjects suggests the existence of a vowel-like pattern. Pattern analysis revealed a unique sound signature, which could be used in non-invasive screening tools.

A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study.

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Tulloh, R M R; Garratt, V; Tagney, J; Turner-Cobb, J; Marques, E; Greenwood, R; Howard, L; Gin-Sing, W; Barton, A; Ewings, P; Craggs, P; Hollingworth, W

2018-01-01

Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial

Local and systemic RAGE axis changes in pulmonary hypertension: CTEPH and iPAH.

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Bernhard Moser

Full Text Available OBJECTIVE: The molecular determinants of chronic thromboembolic pulmonary hypertension (CTEPH and idiopathic pulmonary arterial hypertension (iPAH remain poorly understood. The receptor for advanced glycation endproducts (RAGE and its ligands: HMGB1 and S100A9 are involved in inflammatory disorders. We sought to investigate the role of the RAGE axis in patients with CTEPH undergoing pulmonary endarterectomy (PEA, iPAH undergoing lung transplantation (LuTX. The high pulmonary vascular resistance in CTEPH/iPAH results in pressure overload of the right ventricle. We compared sRAGE measurements to that of patients with aortic valve stenosis (AVS - pressure overload of the left ventricle. METHODS: We enrolled patients with CTEPH(26, iPAH(15, AVS(15 and volunteers(33. Immunohistochemistry with antibodies to RAGE and HMGB1 was performed on PEA specimens and lung tissues. We employed enzyme-linked immunosorbent assays to determine the concentrations of sRAGE, esRAGE, HMGB1 and S100A9 in serum of volunteers and patients with CTEPH, iPAH, AVS before and after PEA, LuTX and aortic valve replacement (AVR. RESULTS: In endarterectomised tissues from patients with CTEPH RAGE and HMGB1 were identified in myofibroblasts (α-SMA+vimentin+CD34-, recanalizing vessel-like structures of distal myofibrotic tissues and endothelium of neointima. RAGE was differentially expressed in prototypical Heath Edwards lesions in iPAH. We found significantly increased serum concentrations of sRAGE, esRAGE and HMGB1 in CTEPH. In iPAH, sRAGE and esRAGE were significantly higher than in controls. Serum concentrations of sRAGE were significantly elevated in iPAH(p<0.001 and CTEPH(p = 0.001 compared to AVS. Serum sRAGE was significantly higher in iPAH compared to CTEPH(p = 0.042 and significantly reduced in AVS compared to controls(p = 0.001. There were no significant differences in sRAGE serum concentrations before and after surgical therapy for CTEPH, iPAH or AVS. CONCLUSIONS: Our

Standards and Methodological Rigor in Pulmonary Arterial Hypertension Preclinical and Translational Research.

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Provencher, Steeve; Archer, Stephen L; Ramirez, F Daniel; Hibbert, Benjamin; Paulin, Roxane; Boucherat, Olivier; Lacasse, Yves; Bonnet, Sébastien

2018-03-30

Despite advances in our understanding of the pathophysiology and the management of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for this devastating disease. Yet, few innovative therapies beyond the traditional pathways of endothelial dysfunction have reached clinical trial phases in PAH. Although there are inherent limitations of the currently available models of PAH, the leaky pipeline of innovative therapies relates, in part, to flawed preclinical research methodology, including lack of rigour in trial design, incomplete invasive hemodynamic assessment, and lack of careful translational studies that replicate randomized controlled trials in humans with attention to adverse effects and benefits. Rigorous methodology should include the use of prespecified eligibility criteria, sample sizes that permit valid statistical analysis, randomization, blinded assessment of standardized outcomes, and transparent reporting of results. Better design and implementation of preclinical studies can minimize inherent flaws in the models of PAH, reduce the risk of bias, and enhance external validity and our ability to distinguish truly promising therapies form many false-positive or overstated leads. Ideally, preclinical studies should use advanced imaging, study several preclinical pulmonary hypertension models, or correlate rodent and human findings and consider the fate of the right ventricle, which is the major determinant of prognosis in human PAH. Although these principles are widely endorsed, empirical evidence suggests that such rigor is often lacking in pulmonary hypertension preclinical research. The present article discusses the pitfalls in the design of preclinical pulmonary hypertension trials and discusses opportunities to create preclinical trials with improved predictive value in guiding early-phase drug development in patients with PAH, which will need support not only from researchers, peer reviewers, and editors but also from

Coenzyme Q supplementation in pulmonary arterial hypertension

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Jacqueline Sharp

2014-01-01

Full Text Available Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH. Because coenzyme Q (CoQ is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8 in comparison to healthy controls (N=7, at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement.

[Obstetric outcome in pregnancy complained with pulmonary hypertension].

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Zhu, C X; Xiong, W; Yang, J; Chen, H Q; Niu, G; Wang, Z L

2017-12-19

Objective: To identify whether pregnancy outcomes vary by the severity of pulmonary hypertension. Methods: A retrospective study was conducted on 78 cases of pregnancies complained with pulmonary hypertension who delivered in the First Affiliated Hospital, Sun Yat-sen University from 2006 to 2016.The selected cases were divided into three groups according to severity of pulmonary hypertension: mild pulmonary hypertension group (mild PAH group) was defined as a mean pulmonary artery pressure 30-49 mmHg, moderate pulmonary hypertension (moderate PAH group) as mean pulmonary artery pressure 50-69 mmHg and severe pulmonary hypertension (severe PAH group) as mean pulmonary artery pressure 70 mmHg or greater.The clinical features, risk pregnant complication, maternal and neonatal outcomes were described between these three groups.Analysis of variance, Chi-square test was used for statistical analysis. Results: The average age of mild, moderate and severe PAH group were (31±5) years old, (31±5) years old and (27±3) years old, respectively ( P =0.050). The rate of natural fertilization ( P =0.414), parity ( P =0.527) and gestational age ( P =0.165) were similar in these three groups. In 78 pregnancies with pulmonary hypertension, 64.9% of pregnancies in mild PAH group was NYHA Ⅰ, 50.0% of moderate PAH group was NYHA Ⅱ and 54.5% of severe PAH group was NYHA Ⅲ( P pulmonary hypertension.But the severity of pulmonary hypertension affect the type of anesthesia.Close monitoring during pregnancy and timely termination of pregnancy can improve the outcome of pregnancy.

Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension

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Pugliese SC

2016-01-01

Full Text Available Steven C Pugliese,1 Todd M Bull1,2 1Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, 2UCD Pulmonary Vascular Disease Center, Division of Pulmonary Sciences and Critical Care Medicine and Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH. Intravenous (IV epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin. Recent Phase III clinical trials have shown the drug to improve exercise tolerance in treatment-naïve PAH patients, but not patients on background oral therapy. Oral treprostinil appears to be most efficacious at higher doses, but its side effect profile and complexities with dosing complicate its use. While oral treprostinil’s current therapeutic role in PAH remains unclear, ongoing studies of this class of medication should help clarify their role in the treatment of PAH. Keywords: oral treprostinil, pulmonary arterial hypertension, selexipag

Pulmonary arterial hypertension in adult congenital heart disease.

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Brida, Margarita; Gatzoulis, Michael A

2018-05-02

Pulmonary arterial hypertension (PAH) is commonly associated with congenital heart disease (CHD) and relates to type of the underlying cardiac defects and repair history. Large systemic to pulmonary shunts may develop PAH if untreated or repaired late. PAH, when present, markedly increases morbidity and mortality in patients with CHD. Significant progress has been made for patients with Eisenmenger syndrome in pathophysiology, prognostication and disease-targeting therapy (DTT), which needs to be applied to routine patient care. Patients with PAH-CHD and systemic to pulmonary shunting may benefit from late defect closure if pulmonary vascular resistance (PVR) is still normal or near normal. Patients with PAH and coincidental defects, or previous repair of CHD should be managed as those with idiopathic PAH. Patients with a Fontan circulation, despite not strictly fulfilling criteria for PAH, may have elevated PVR; recent evidence suggests that they may also benefit from DTT, but more data are required before general recommendations can be made. CHD-PAH is a lifelong, progressive disease; patients should receive tertiary care and benefit from a proactive DTT approach. Novel biomarkers and genetic advances may identify patients with CHD who should be referred for late defect closure and/or patients at high risk of developing PAH despite early closure in childhood. Ongoing vigilance for PAH and further controlled studies are clearly warranted in CHD. © 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.

The Role of Exercise Testing in the Modern Management of Pulmonary Arterial Hypertension

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Martin K. Johnson

2014-05-01

Full Text Available A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT has been used as a primary outcome measure to enable the licensing of many of the medications used for this condition. Recent reviews have questioned the validity of this test as a surrogate of clinical outcomes. At the same time, other questions are emerging where exercise testing may be the solution. With the rise in understanding of genetic markers of idiopathic PAH (IPAH, the screening of an otherwise healthy population for incipient pulmonary hypertension (PH will be required. The proliferation in treatment choices and identification of populations with PH where PAH treatment is not indicated, such as left heart and lung disease, requires more definitive differentiation from patients with PAH. There is a continuing question about the existence and clinical relevance of exercise induced PAH as a cause of unexplained dyspnoea and fatigue and as a latent phase of resting PH. This review presents a summary and critical analysis of the current role of exercise testing in PAH and speculates on future trends.

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.

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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 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.

Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension

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Francisca Gavilanes

2014-12-01

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

Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT

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

2009-11-15

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

Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT

International Nuclear Information System (INIS)

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

2009-01-01

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

HMGB1 promotes the development of pulmonary arterial hypertension in rats.

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Yukari Sadamura-Takenaka

Full Text Available Pulmonary arterial hypertension (PAH is characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. However, the molecular and cellular mechanisms driving inflammation have not been fully elucidated.To elucidate the roles of high mobility group box 1 protein (HMGB1, a ubiquitous DNA-binding protein with extracellular pro-inflammatory activity, in a rat model of PAH.Male Sprague-Dawley rats were administered monocrotaline (MCT. Concentrations of HMGB1 in bronchoalveolar lavage fluid (BALF and serum, and localization of HMGB1 in the lung were examined over time. The protective effects of anti-HMGB1 neutralizing antibody against MCT-induced PAH were tested.HMGB1 levels in BALF were elevated 1 week after MCT injection, and this elevation preceded increases of other pro-inflammatory cytokines, such as TNF-α, and the development of PAH. In contrast, serum HMGB1 levels were elevated 4 weeks after MCT injection, at which time the rats began to die. Immunohistochemical analyses indicated that HMGB1 was translocated to the extranuclear space in periarterial infiltrating cells, alveolar macrophages, and bronchial epithelial cells of MCT-injected rats. Anti-HMGB1 neutralizing antibody protected rats against MCT-induced lung inflammation, thickening of the pulmonary artery wall, and elevation of right ventricular systolic pressure, and significantly improved the survival of the MCT-induced PAH rats.Our results identify extracellular HMGB1 as a promoting factor for MCT-induced PAH. The blockade of HMGB1 activity improved survival of MCT-induced PAH rats, and thus might be a promising therapy for the treatment of PAH.

Changes of plasma ADM and ANP of pulmonary artery hypertension in patients with obstructive sleep apnea syndrome

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Gao Zhi; Zhong Jian; Sheng Chunyong; Xu Shouhong

2005-01-01

Objective: To explore the incidence of pulmonary artery hypertension (PAH) and changes of plasma adrenomedullin (ADM) and atrial natriuretic polypeptide (ANP) in patients with obstructive sleep apnea syndrome (OSAS). Methods: 32 healthy middle- and elder-aged cases were randomly selected as control group, 61 cases were confirmed clinically with OSAS. The pressure of pulmonary artery was measured with real time gray scale two-dimensional ultrasonic tomography, the blood plasma levels of ADM and ANP were determined with radioimmunoassay method. Results: Among 61 OSAS patients, 26 of them presented with PAH, its incidence in OSAS was 42.6%. The plasma level of ADM in OSAS with non-PAH group had statistical difference compared with control group ( P < 0.05 ) , also there were significant differences between PAH, non-PAH and control group (P<0.001). Concurrently, the plasma level of ANP in OSAS with PAH, non-PAH also had significant differences compared with control group (P<0.001). Conclusions: There was high incidence of PAH in OSAS patients. The plasma levels of ADM and ANP positively correlated with PAH. ANP played a role in the pathophysiologic genesis of PAH. (authors)

The changing landscape of pulmonary arterial hypertension and implications for patient care

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Marius M. Hoeper

2014-12-01

Full Text Available Registries have provided a wealth of information on the clinical and disease characteristics of patients living with pulmonary arterial hypertension (PAH since the 1980s. Certain PAH demographics, such as the prevalence of various PAH subgroups and preponderance of female patients, appear to have remained stable over time. Contemporary registry data indicate that the average age of patients diagnosed with PAH has increased, at least in the Western world. Older patients with PAH are more likely to be diagnosed with a more advanced stage of the disease, have lower exercise capacity and present with multiple comorbidities. They also have worse survival compared with younger patients. Within the PAH population, there is also a subset of patients with a lower diffusing capacity of the lung for carbon monoxide who are generally older and display more severe disease characteristics. This review discusses the implications that the increased age of the PAH population at diagnosis has on the treatment and management of the disease, as well as the need for earlier and improved diagnosis in these patients.

Surgical outcome of severe pulmonary arterial hypertension secondary to left-to-right shunt lesions

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Cha Gon Lee

2010-02-01

Full Text Available Purpose : Despite recent advances in pulmonary hypertension management and surgery, appropriate guidelines remain to be developed for operability in congenital heart disease with pulmonary artery hypertension (PAH. Our aim was to evaluate clinical outcomes of patients with severe PAH who underwent surgical closure of left-to-right shunt lesions (LRSL on the basis of pulmonary reactivity. Methods : We retrospectively reviewed 21 patients who underwent surgical closure of LRSL with severe PAH (?#248; Wood unit from January 1995 to April 2009. The median age at operation was 26 years. Atrial septal defect, ventricular septal defect (VSD, VSD and patent ductus arteriosus (PDA, and PDA was present in 11, 4, 4, and 2 patients, respectively. Results : Operability was based on vasoreactivity of PAH. Of the 21 patients, 5 showed response to pulmonary vasodilator therapy and 8 showed vasoreactivity after balloon occlusion of defects. The remaining 8 patients were considered operable because of significant left-to-right shunt (Qp/Qs ?#241;.5. Five patients underwent total closure of defects and 16 were left with small residual shunts. The median follow-up duration was 32 months. There was no significant postoperative mortality or morbidity. Systolic pulmonary artery pressure (PAP decreased in all but 2 patients. All patients except 1 showed improvement of New York Heart Association functional class. Conclusion : Closure of LRSL in patients with severe PAH on the basis of pulmonary vasoreactivity seems reasonable. PAP and clinical symptoms improved in most patients. Further research is needed for the evaluation of long-term results.

Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification

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van Riel, Annelieke C. M. J.; Schuuring, Mark J.; van Hessen, Irene D.; Zwinderman, Aielko H.; Cozijnsen, Luc; Reichert, Constant L. A.; Hoorntje, Jan C. A.; Wagenaar, Lodewijk J.; Post, Marco C.; van Dijk, Arie P. J.; Hoendermis, Elke S.; Mulder, Barbara J. M.; Bouma, Berto J.

2014-01-01

The aging congenital heart disease (CHD) population is prone to develop a variety of sequelae, including pulmonary arterial hypertension (PAH). Previous prevalence estimates are limited in applicability due to the use of tertiary centers, or database encoding only. We aimed to investigate the

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

OpenAIRE

QIAO, FENG; ZOU, ZHITIAN; LIU, CHUNHUI; ZHU, XIAOFENG; WANG, XIAOQIANG; YANG, CHENGPENG; JIANG, TENGJIAO; CHEN, YING

2016-01-01

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

Prognostic factors in pulmonary arterial hypertension: assessing the course of the disease

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L.S. Howard

2011-12-01

Full Text Available The practical management of pulmonary arterial hypertension (PAH requires an accurate assessment of disease severity and prognosis. A number of prognostic indicators are known to be associated with patient outcome, and recent treatment guidelines advocate using such parameters to guide management decisions. Although PAH is characterised by the presence of pulmonary vasculopathy, it is the response of the right ventricle to an increased afterload that is the greatest determinant of a patient's symptoms and survival; thus, measurements that capture right ventricular function provide the best potential to assess PAH severity. One challenge is to understand how the tests we use in everyday clinical practice relate to right heart function in PAH patients, and how current measures can be improved and developed to optimise assessment of disease status and progress. Future research in the field of PAH should focus on how best to assess right heart function, and which measures or combination of measures provide the most relevant information for the individual patient.

Emergency Management of Hypertension in Children

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Dinesh Singh

2012-01-01

Full Text Available Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH, particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information.

The role of disturbed blood flow in the development of pulmonary arterial hypertension : lessons from preclinical animal models

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Dickinson, Michael G.; Bartelds, Beatrijs; Borgdorff, Marinus A. J.; Berger, Rolf M. F.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the

Liver cirrhosis and arterial hypertension

DEFF Research Database (Denmark)

Henriksen, Jens Henrik; Møller, Søren

2006-01-01

blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension.

Science.gov (United States)

Price, Laura C; Dimopoulos, Konstantinos; Marino, Philip; Alonso-Gonzalez, Rafael; McCabe, Colm; Kemnpy, Aleksander; Swan, Lorna; Boutsikou, Maria; Al Zahrani, Ahmed; Coghlan, Gerry J; Schreiber, Benjamin E; Howard, Luke S; Davies, Rachel; Toshner, Mark; Pepke-Zaba, Joanna; Church, Alistair C; Peacock, Andrew; Corris, Paul A; Lordan, James L; Gaine, Sean; Condliffe, Robin; Kiely, David G; Wort, Stephen John

2017-11-01

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Integrated care and optimal management of pulmonary arterial hypertension

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Geoff Strange

2009-05-01

Full Text Available Geoff Strange1, Robin Fowler2, Corina Jary2, Brad Dalton3, Simon Stewart4, Eli Gabbay51Epidemiology and Preventative Medicine, Monash University, VIC, Australia; 2Royal Perth Hospital and Curtin University, Perth, WA, Australia; 3University of Tasmania, Launceston, TAS, Australia; 4Baker Heart Research Institute, Melbourne, VIC, Australia; 5Royal Perth Hospital and University of Western Australia, Perth, WA, AustraliaAbstract: 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. Keywords: pulmonary hypertension, multidisciplinary care, systemic sclerosis, diagnostic protocol

Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient

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Christopher J Valerio

2009-08-01

Full Text Available Christopher J Valerio, John G CoghlanDepartment of Cardiology, Royal Free Hospital, London, UKAbstract: Pulmonary arterial hypertension (PAH is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA that has been shown in a large randomized placebo-controlled trial (BREATHE-1 to be effective at improving exercise tolerance in patients with PAH in functional class III and IV. Further studies have been conducted showing: benefit in smaller subgroups of PAH, eg, congenital heart disease, efficacy in combination with other PAH therapies, eg, sildenafil, improved long-term survival compared with historical controls. More recently, controlled trials of new ERAs have included patients with milder symptoms; those in functional class II. Analysis of the functional class II data is often limited by small numbers. These trials have generally shown a similar treatment effect to bosentan, but there are no controlled trials directly comparing these new ERAs. The EARLY trial exclusively enrolled functional class II patients and assessed hemodynamics at 6 months. Though significant, the reduction in pulmonary vascular resistance is merely a surrogate marker for the intended aim of delaying disease progression. Significant adverse effects associated with bosentan include edema, anemia and transaminase elevation. These may preclude a long duration of treatment. Further studies are required to determine optimum treatment strategy in mild disease.Keywords: pulmonary arterial hypertension, bosentan, endothelin-1 receptor antagonist

Liver cirrhosis and arterial hypertension

DEFF Research Database (Denmark)

Henriksen, Jens Henrik; Møller, Søren

2006-01-01

blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development......Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

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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.

Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension.

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Mainguy, Vincent; Malenfant, Simon; Neyron, Anne-Sophie; Bonnet, Sébastien; Maltais, François; Saey, Didier; Provencher, Steeve

2013-08-01

Exercise tolerance in pulmonary arterial hypertension (PAH) is most commonly assessed by the 6-min walk test (6MWT). Whether endurance exercise tests are more responsive than the 6MWT remains unknown. 20 stable PAH patients (mean±sd age 53±15 years and mean pulmonary arterial pressure 44±16 mmHg) already on PAH monotherapy completed the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) before and after the addition of sildenafil citrate 20 mg three times daily or placebo for 28 days in a randomised double-blind crossover setting. Pre- or post-placebo tests were used to assess repeatability of each exercise test, whereas pre- or post-sildenafil citrate tests were used to assess their responsiveness. Sildenafil citrate led to placebo-corrected changes in exercise capacity of 18±25 m (p = 0.02), 58±235 s (p = 0.58) and 29±77 s (p = 0.09) for the 6MWT, the ESWT and the CET, respectively. The 6MWT was associated with a lower coefficient of variation between repeated measures (3% versus 18% versus 13%), resulting in a higher standardised response mean compared with endurance tests (0.72, 0.25 and 0.38 for the 6MWT, the ESWT and the CET, respectively). The 6MWT had the best ability to capture changes in exercise capacity when sildenafil citrate was combined with patients' baseline monotherapy, supporting its use as an outcome measure in PAH.

DNA Damage and Pulmonary Hypertension

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

2016-01-01

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

Chronic use of PAH-specific therapy in World Health Organization Group III Pulmonary Hypertension: a systematic review and meta-analysis.

Science.gov (United States)

Prins, Kurt W; Duval, Sue; Markowitz, Jeremy; Pritzker, Marc; Thenappan, Thenappan

2017-03-01

Pulmonary hypertension (PH) complicating chronic obstructive pulmonary disease (COPD-PH) and interstitial lung disease (ILD-PH) (World Health Organization [WHO] Group III PH) increases medical costs and reduces survival. Despite limited data, many clinicians are using pulmonary arterial hypertension (PAH)-specific therapy to treat WHO Group III PH patients. To further investigate the utility of PAH-specific therapy in WHO Group III PH, we performed a systematic review and meta-analysis. Relevant studies from January 2000 through May 2016 were identified in the MEDLINE, EMBASE, and COCHRANE electronic databases and www.clinicaltrials.gov. Change in six-minute walk distance (6MWD) was estimated using random effects meta-analysis techniques. Five randomized controlled trials (RCTs) in COPD-PH (128 placebo or standard treatment and 129 PAH-medication treated patients), two RCTs in ILD-PH (23 placebo and 46 treated patients), and four single-arm clinical trials (50 patients) in ILD-PH were identified. Treatment in both COPD-PH and ILD-PH did not worsen hypoxemia. Symptomatic burden was not consistently reduced but there were trends for reduced pulmonary artery pressures and pulmonary vascular resistance with PAH-specific therapy. As compared to placebo, 6MWD was not significantly improved with PAH-specific therapy in the five COPD-PH RCTs (42.7 m; 95% confidence interval [CI], -1.0 - 86.3). In the four single-arm studies in ILD-PH patients, there was a significant improvement in 6MWD after PAH-specific treatment (46.2 m; 95% CI, 27.9-64.4), but in the two ILD-PH RCTs there was not an improvement (21.6 m; 95% CI, -17.8 - 61.0) in exercise capacity when compared to placebo. Due to the small numbers of patients evaluated and inconsistent beneficial effects, the utility of PAH-specific therapy in WHO Group III PH remains unproven. A future clinical trial that is appropriately powered is needed to definitively determine the efficacy of this widely implemented treatment

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

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Dong-Mei Jiang

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

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

International Nuclear Information System (INIS)

Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

2014-01-01

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

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-18

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

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

Science.gov (United States)

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

2013-03-01

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

Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially fatal combination.

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

2012-07-01

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

Pediatric Pulmonary Arterial Hypertension and Hyperthyroidism: A Potentially Fatal Combination

Science.gov (United States)

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

2012-01-01

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

Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

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M. Rizzo

2011-09-01

Full Text Available Objective: Pulmonary arterial hypertension (PAH is a rare but severe complication of connective tissue diseases (CTD, with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases, SLE (2 cases, mixed connective tissue disease (1 case and polymyositis (1 case attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

Genetics Home Reference: pulmonary arterial hypertension

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... 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 ...

Challenges in the diagnosis and treatment of pulmonary arterial hypertension.

LENUS (Irish Health Repository)

2012-12-01

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

[Evaluation of exercise capacity in pulmonary arterial hypertension].

Science.gov (United States)

Demir, Rengin; Küçükoğlu, Mehmet Serdar

2010-12-01

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by increased pulmonary vascular resistance that leads to right ventricular failure. The most common clinical features of PAH are dyspnea and exercise intolerance. Measurement of exercise capacity is of considerable importance for the assessment of disease severity as well as routine monitoring of disease. Maximal, symptom-limited, cardiopulmonary exercise test (CPET) is the gold standard for the evaluation of exercise capacity, whereby functions of several systems involved in exercise can be assessed, including cardiovascular, respiratory, and metabolic systems. However, in order to derive the most useful diagnostic information on physiologic limitations to exercise, CPET requires maximal effort of the patient, which can be difficult and risky for some severely ill patients. Moreover, it requires specific exercise equipment and measurement systems, and experienced and trained personnel. Thus, routine clinical use of CPET to assess exercise capacity in patients with PAH may not always be feasible. A practical and simple alternative to CPET to determine exercise capacity is the 6-minute walk test (6MWT). It is simple to perform, safe, and reproducible. In contrast to CPET, the 6MWT reflects a submaximal level of exertion that is more consistent with the effort required for daily physical activities. This review focuses on the role of CPET and 6MWT in patients with PAH.

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

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

2005-06-07

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

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

Science.gov (United States)

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

2007-01-01

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

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

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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.

Systematic Review of the Economic Burden of Pulmonary Arterial Hypertension.

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Gu, Shuyan; Hu, Huimei; Dong, Hengjin

2016-06-01

Pulmonary arterial hypertension (PAH), as a life-threatening disease with no efficient cure, may impose a tremendous economic burden on patients and healthcare systems. However, most existing studies have mainly emphasised epidemiology and medications, while large observational studies reporting on the economic burden are currently lacking. To review and evaluate evidence on the costs of PAH and the cost effectiveness of PAH treatments, and to summarise the corresponding cost drivers. Systematic literature searches were conducted in English-language databases (PubMed, Web of Science, ScienceDirect) and Chinese-language databases (China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP) to identify studies (published from 2000 to 2014) assessing the costs of PAH or the cost effectiveness of PAH treatments. The search results were independently reviewed and extracted by two reviewers. Costs were converted into 2014 US dollars. Of 1959 citations identified in the initial search, 19 papers were finally included in this analysis: eight on the economic burden of PAH and 11 on economic evaluation of PAH treatments. The economic burden on patients with PAH was rather large, with direct healthcare costs per patient per month varying from $2476 to $11,875, but none of the studies reported indirect costs. Sildenafil was universally reported to be a cost-effective treatment, with lower costs and better efficacy than other medications. Medical costs were reported to be the key cost drivers. The economic burden of patients with PAH is substantial, while the paucity of comprehensive country-specific evidence in this area and the lack of reports on indirect costs of PAH warrant researchers' concern, especially in China.

High prevalence of occult left heart disease in scleroderma-pulmonary hypertension.

Science.gov (United States)

Fox, Benjamin D; Shimony, Avi; Langleben, David; Hirsch, Andrew; Rudski, Lawrence; Schlesinger, Robert; Eisenberg, Mark J; Joyal, Dominique; Hudson, Marie; Boutet, Kim; Serban, Alexandrina; Masetto, Ariel; Baron, Murray

2013-10-01

Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP)≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP>15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH.

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

International Nuclear Information System (INIS)

Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

2015-01-01

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

Energy Technology Data Exchange (ETDEWEB)

Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

2015-09-25

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

[Secondary Arterial Hypertension: Uncertainties in Diagnosis].

Science.gov (United States)

Dinis, Paulo Gomes; Cachulo, Maria Carmo; Fernandes, Andreia; Paiva, Luis; Gonçalves, Lino

2017-06-30

Arterial hypertension is regarded today as a global public health problem, and the prevalence rate in Portugal is 26.9%. According to the etiology, is classified into primary or secondary arterial hypertension. In about 90% of cases it is not possible to establish a cause, so is called primary arterial hypertension. In the remaining 5 to 10%, it can be identified secondary causes, which are potentially treatable. For secondary arterial hypertension study to be cost-effective, it is essential to understand which patients investigate, and evaluate the best strategy to adopt. The main causes identified as responsible for secondary arterial hypertension are: kidney disease; endocrine and vascular diseases and obstructive sleep apnea. Among these some are consensual, and others more controversial in the literature. In this regard we present two cases of arterial hypertension, which are potentially secondary in etiology, but still focus of debate.

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

Science.gov (United States)

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

2018-04-20

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

[Pulmonary hypertension: definition, classification and treatments].

Science.gov (United States)

Jutant, Etienne-Marie; Humbert, Marc

2016-01-01

Pulmonary hypertension (PH) is a cardio-pulmonary disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Its definition is an increase in mean pulmonary artery pressure (mPAP) \\hbox{$\\geqslant $} ⩾ 25 mmHg at rest, leading to right heart failure and ultimately death. The clinical classification of pulmonary hypertension (PH) categorizes PH into groups which share similar pathophysiological and hemodynamic characteristics and treatments. Five groups of disorders that cause PH are identified: pulmonary arterial hypertension (Group 1) which is a pre-capillary PH, defined by a normal pulmonary artery wedge pressure (PAWP) \\hbox{$\\leqslant $} ⩽ 15 mmH, due to remodelling of the small pulmonary arteries (15 mmHg; pulmonary hypertension due to chronic lung disease and/or hypoxia (Group 3); chronic thrombo-embolic pulmonary hypertension (Group 4); and pulmonary hypertension due to unclear and/or multifactorial mechanisms (Group 5). PAH (PH group 1) can be treated with agents targeting three dysfunctional endothelial pathways of PAH: nitric oxide (NO) pathway, endothelin-1 pathway and prostacyclin pathway. Patients at low or intermediate risk can be treated with either initial monotherapy or initial oral combination therapy. In patients at high risk initial combination therapy including intravenous prostacyclin analogues should be considered. Patients with inadequate clinical response to maximum treatment (triple therapy with an intravenous prostacyclin) should be assessed for lung transplantation. Despite progresses, PAH remains a fatal disease with a 3-year survival rate of 58%. Treatment of group 2, group 3 and group 5 PH is the treatment of the causal disease and PAH therapeutics are not recommended. Treatment of group 4 PH is pulmonary endarteriectomy if patients are eligible, otherwise balloon pulmonary angioplasty and/or medical therapy can be considered. © Société de Biologie

Anticipated classes of new medications and molecular targets for pulmonary arterial hypertension

Science.gov (United States)

Morrell, Nicholas W.; Archer, Stephen L.; DeFelice, Albert; Evans, Steven; Fiszman, Monica; Martin, Thomas; Saulnier, Muriel; Rabinovitch, Marlene; Schermuly, Ralph; Stewart, Duncan; Truebel, Hubert; Walker, Gennyne; Stenmark, Kurt R.

2013-01-01

Pulmonary arterial hypertension (PAH) remains a life-limiting condition with a major impact on the ability to lead a normal life. Although existing therapies may improve the outlook in some patients there remains a major unmet need to develop more effective therapies in this condition. There have been significant advances in our understanding of the genetic, cell and molecular basis of PAH over the last few years. This research has identified important new targets that could be explored as potential therapies for PAH. In this review we discuss whether further exploitation of vasoactive agents could bring additional benefits over existing approaches. Approaches to enhance smooth muscle cell apotosis and the potential of receptor tyrosine kinase inhibition are summarised. We evaluate the role of inflammation, epigenetic changes and altered glycolytic metabolism as potential targets for therapy, and whether inherited genetic mutations in PAH have revealed druggable targets. The potential of cell based therapies and gene therapy are also discussed. Potential candidate pathways that could be explored in the context of experimental medicine are identified. PMID:23662201

Hipertensão arterial pulmonar e doenças da tireoide Pulmonary arterial hypertension and thyroid disease

Directory of Open Access Journals (Sweden)

Denise Rossato Silva

2009-02-01

Full Text Available Estudos recentes têm sugerido uma associação entre hipertensão arterial pulmonar (HAP e tireoidopatias (hipotireoidismo e hipertireoidismo. Esta associação tem um bom prognóstico, porque o aumento na pressão da artéria pulmonar geralmente é leve e reversível com o tratamento da tireoidopatia. O mecanismo exato envolvido na patogênese desta associação não está estabelecido, e a influência direta dos hormônios da tireoide e a autoimunidade são consideradas como hipóteses. Devido à alta prevalência de doenças da tireoide em pacientes com HAP, testes de função tireoidiana devem ser considerados na investigação de todo paciente com HAP. Neste artigo de revisão, descrevemos a prevalência de HAP em pacientes com doenças da tireoide e a prevalência de tireoidopatias em pacientes com HAP, assim como destacamos os principais efeitos das doenças da tireoide no sistema respiratório. A seguir, relatamos os efeitos do tratamento destas patologias.Recent studies have suggested an association between pulmonary arterial hypertension (PAH and thyroid diseases (hypothyroidism and hyperthyroidism. This combination has a good prognosis, because the increase in the pulmonary artery pressure is usually slight and reverses after the treatment of the thyroid disease. Although the exact mechanism involved in the pathogenesis of this combination has not yet been established, it has been hypothesized that thyroid hormones and autoimmunity have a direct influence. Due to the high prevalence of thyroid disease in patients with PAH, thyroid function tests should be considered in the investigation of every patient with PAH. In this review, we describe the prevalence of PAH in patients with thyroid diseases and the prevalence of thyroid disease in patients with PAH, as well as addressing the principal effects that thyroid diseases have on the respiratory system. In addition, we report the treatment effects in patients with these diseases.

Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

Science.gov (United States)

Johnson, Jennifer A; Hemnes, Anna R; Perrien, Daniel S; Schuster, Manfred; Robinson, Linda J; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R; Tada, Yuji; Harral, Julie W; Talati, Megha; Lane, Kirk B; Fagan, Karen A; West, James

2012-03-01

The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

Impact of pulmonary arterial hypertension and its therapy on indices of heart rate variability.

Science.gov (United States)

Can, Mehmet Mustafa; Kaymaz, Cihangir; Pochi, Nartilla; Aktimur, Tugba

2013-08-01

To compare heart rate variability (HRV) indices between pulmonary arterial hypertension (PAH) patients and controls, and to investigate whether therapy improves heart rhythm. Thirty-eight patients and 20 controls underwent Holter monitoring. HRV was analyzed before and after PAH therapy. Various time, and frequency domain indices of HRV analysis including standard deviation of all normal-to-normal intervals, standard deviation of mean values for all normal-to-normal intervals over 5 min, and square root of the mean square differences of successive RR intervals were recorded and analyzed before and after 1 year of PAH therapy. Significant differences with regard to diminished physical capacity, impared cardiac output, increased BNP in PAH cohort; HRV indices were diminished compared to controls and no differences between before and after PAH therapy with respect to analysis of HRV. Patients exhibited depressed HRV and therapy failed to improve HRV indices suggesting urgent unmet need for better therapeutic options. Patients with PAH exhibit severely depressed HRV. Surprisingly, PAH specific therapy for 1 year with phosphodiesterase- 5 inhibitor, prostacyclin analogue, endhotelin receptor antagonist, or their combination failed to improve HRV indices suggesting urgent unmet need for better therapeutic options.

Pulmonary arterial hypertension: tailoring treatment to risk in the current era

Directory of Open Access Journals (Sweden)

Sean Gaine

2017-12-01

Full Text Available Recent advances in the treatment of pulmonary arterial hypertension (PAH have led to improved patient outcomes. Multiple PAH therapies are now available and optimising the use of these drugs in clinical practice is vital. In this review, we discuss the management of PAH patients in the context of current treatment guidelines and supporting clinical evidence. In clinical practice, considerable emphasis is placed on the importance of making treatment decisions guided by each patient's risk status, which should be assessed using multiple prognostic parameters. As PAH is a progressive disease, regular assessments are essential to ensure that any change in risk is detected in a timely manner and treatment is adjusted accordingly. With the availability of therapies that target three different pathogenic pathways, combination therapy is now the standard of care. For most patients, this involves dual combination therapy with agents targeting the endothelin and nitric oxide pathways. Therapies targeting the prostacyclin pathway should be added for patients receiving dual combination therapy who do not achieve a low-risk status. There is also a need for a holistic approach to treatment beyond pharmacological therapies. Implementation of all these approaches will ensure that PAH patients receive maximal benefit from currently available therapies.

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

Science.gov (United States)

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

Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension.

Science.gov (United States)

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L

2016-08-01

Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.

Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease

NARCIS (Netherlands)

Engelfriet, Peter M.; Duffels, Marielle G. J.; Möller, Thomas; Boersma, Eric; Tijssen, Jan G. P.; Thaulow, Erik; Gatzoulis, Michael A.; Mulder, Barbara J. M.

2007-01-01

AIM: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. METHODS AND RESULTS: From the database of the Euro Heart Survey on adult congenital heart

Six-minute walking distance and decrease in oxygen saturation during the six-minute walk test in pediatric pulmonary arterial hypertension

NARCIS (Netherlands)

Douwes, Johannes M.; Hegeman, Anneke K.; van der Krieke-van der Horst, Merel; Roofthooft, Marcus T. R.; Hillege, Hans L.; Berger, Rolf M. F.

2016-01-01

Objective: To investigate the prognostic value of the 6-minute walking distance (6-MWD), transcutaneous saturation (tcSO2) and heart rate (HR) obtained during the 6-minute walk test (6-MWT) in pediatric pulmonary arterial hypertension (PAH). Methods: This was an observational study with forty-seven

Pulmonary Hypertension

Science.gov (United States)

Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

2015-01-01

Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

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

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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.

Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.

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Wei-Chun Huang

Full Text Available Pulmonary arterial hypertension (PAH is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs and iPSC-conditioned medium (iPSC CM were explored in monocrotaline (MCT-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1β, IL-6, IL-12α, IL-12β, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

Science.gov (United States)

Riccieri, Valeria; Vasile, Massimiliano; Iannace, Nicoletta; Stefanantoni, Katia; Sciarra, Iliana; Vizza, Carmine D; Badagliacca, Roberto; Poscia, Roberto; Papa, Silvia; Mezzapesa, Mario; Nocioni, Martina; Valesini, Guido

2013-08-01

Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

Percutaneous device closure of patent ductus arteriosus with pulmonary artery hypertension: long-term results.

Science.gov (United States)

Vijayalakshmi, Ishwarappa Balekundri; Setty, Natraj; Narasimhan, Chitra; Singla, Vivek; Manjunath, Cholenahalli Nanjappa

2014-12-01

Device closure of patent ductus arteriosus (PDA) is treatment of choice. But device closure in presence of pulmonary artery hypertension (PAH) remains a challenge. Data on patient selection, technical considerations, and complications are limited. To know the challenges and efficacy of device closure of PDA with PAH. Out of 1,325 cases of device closure of PDA, 246 (18.6%) with PAH formed the study material. To test the feasibility, chosen device is used to occlude PDA for ten minutes without oxygen inhalation. The device is released only if PAH reduced. PAH decreased in all except in 1 patient after closure with muscular ventricular septal occluder (MVSDO), pulmonary artery pressure (PAP) transiently increased (became supra-systemic), without significant reduction in aortic pressure. Device embolized in 8 patients (3.3%). Percutaneous retrieval was done in 4 (by snare in 2 and by fixing the cable to device in 2) and replaced with bigger devices. The surgical removal of the embolized MVSDO and ligation was done in 4 cases. All patients were on oral sildenafil and bosentan until PAP regressed to normal. Follow up was from 6 months to 9 years. No residual shunt in any patient on follow-up. The PAP regressed to normal in all except 5 cases (2.03%) of Down's syndrome with systemic PAP. Device closure of PDA with PAH is feasible, safe in all age groups. Temporary PDA occlusion with device is effective and time saving for evaluating pulmonary vascular reactivity. Device embolization in aorta is higher with severe PAH. Novel method of retrieval is effective. © 2014, Wiley Periodicals, Inc.

Randomised controlled trial examining the effect of an outpatient exercise training programme on haemodynamics and cardiac MR parameters of right ventricular function in patients with pulmonary arterial hypertension: the ExPAH study protocol.

Science.gov (United States)

Chia, Karen S W; Faux, Steven G; Wong, Peter K K; Holloway, Cameron; Assareh, Hassan; McLachlan, Craig S; Kotlyar, Eugene

2017-02-06

Pulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular function and progressive dyspnoea. Current guidelines recommend exercise training (grade IIa, level B). However, many questions remain regarding the mechanisms of improvement, intensity of supervision and optimal frequency, duration and intensity of exercise. This study will assess the effect of an outpatient rehabilitation programme on haemodynamics and cardiac right ventricular function in patients with pulmonary arterial hypertension (PAH), a subgroup of PH. This randomised controlled trial involves both a major urban tertiary and smaller regional hospital in New South Wales, Australia. The intervention will compare an outpatient rehabilitation programme with a control group (home exercise programme). Participants will be stable on oral PAH-specific therapy. The primary outcome measure will be right ventricular ejection fraction measured by cardiac MRI. Secondary outcomes will include haemodynamics measured by right heart catheterisation, endurance, functional capacity, health-related quality of life questionnaires and biomarkers of cardiac function and inflammation. Ethical approval has been granted by St Vincent's Hospital, Sydney (HREC/14/SVH/341). Results of this study will be disseminated through presentation at scientific conferences and in scientific journals. ACTRN12615001041549; pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Pulmonary arterial hypertension associated with human immunodeficiency virus infection: study of 4 cases].

Science.gov (United States)

Pousada, Guillermo; Baloira, Adolfo; Castro-Añón, Olalla; Valverde, Diana

2016-04-15

Pulmonary arterial hypertension (PAH) is a rare and progressive disease that can be inherited as autosomal dominant form. The BMPR2, ACVRL1 and ENG genes are main genes involved in the pathology. PAH associated to human immunodeficiency virus (HIV) is another rare disease with a low incidence, prevalence and survival. The main objective of this analysis was to study the clinical and molecular characteristics of PAH associated to HIV patients. We present 4 cases of HIV patients who developed PAH and have been treated with ambrisentan. Pathogenic mutations have been identify in analyzed genes in 3 of the four analyzed patients. In addition, these patients present other changes classified as benign after a thorough in silico analysis. We identified some changes in genetic modifiers that predispose to these patients to more severe phenotype. The clinical analysis can help to define monitoring for these patients and the administration of appropriate treatment. These patients also have shown several pathogenic mutations. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: Mitochondrial inhibition as driver of cardiac failure?

NARCIS (Netherlands)

G. Balestra (Gianmarco); E.G. Mik (Egbert); O. Eerbeek (Otto); P. Specht (Patricia); W.J. van der Laarse (Willem J.); C.J. Zuurbier (Coert J.)

2015-01-01

textabstractBackground: The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at

EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

Directory of Open Access Journals (Sweden)

Zhan-Li Shi

2018-01-01

Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

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

Science.gov (United States)

Saxena, Anita

2012-01-01

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

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

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Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

2018-03-01

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p L-arginine than patients with LVSD (p L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Out of proportion pulmonary hypertension in obstructive lung diseases.

Science.gov (United States)

Chatterjee, Kshitij; Tarawneh, Ahmad R; Alam, Shoaib

2018-03-01

Pulmonary hypertension is common (25-90%) in chronic obstructive pulmonary diseases (COPDs). Severe pulmonary hypertension, however, is quite rare (1-3%). The term 'out of proportion' pulmonary hypertension is still widely used. New guidelines instead propose to use the term 'Severe pulmonary hypertension' if mean pulmonary arterial pressure at least 35 mmHg or cardiac index (CI) is less than 2.0 l/min/m on right heart catheterization (RHC). Why only a minority of COPD patients develop severe pulmonary hypertension is unclear. When present, severe pulmonary hypertension in COPD is associated with increased dyspnea and decreased survival and often does not closely correlate with degree of obstructive abnormality on pulmonary function testing. COPD patients with severe pulmonary hypertension experience circulatory limitation at maximum exercise, and not ventilatory limitation, which is typical for moderate-to-severe COPD patients with no or moderate pulmonary hypertension. There is no conclusive evidence to support or completely reject the possibility of the use of specific pulmonary arterial hypertension (PAH) therapies in pulmonary hypertension associated with COPD. In mild-to-moderate COPD patients who have severe and progressive symptoms, and have evidence of severe pulmonary hypertension on RHC, specific PAH therapies may be used similar to WHO group-I PAH guidelines.

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

Science.gov (United States)

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

2016-05-01

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Load Adaptability in Patients With Pulmonary Arterial Hypertension.

Science.gov (United States)

Amsallem, Myriam; Boulate, David; Aymami, Marie; Guihaire, Julien; Selej, Mona; Huo, Jennie; Denault, Andre Y; McConnell, Michael V; Schnittger, Ingela; Fadel, Elie; Mercier, Olaf; Zamanian, Roham T; Haddad, Francois

2017-09-01

Right ventricular (RV) adaptation to pressure overload is a major prognostic factor in patients with pulmonary arterial hypertension (PAH). The objectives were first to define the relation between RV adaptation and load using allometric modeling, then to compare the prognostic value of different indices of load adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200) were included. Load adaptability was assessed using 3 approaches: (1) surrogates of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2) simple ratio of function and load (e.g., tricuspid annular plane systolic excursion/right ventricular systolic pressure), and (3) indices assessing the proportionality of adaptation using allometric pressure-function or size modeling. Proportional hazard modeling was used to compare the hazard ratio for the outcome of death or lung transplantation. The mean age of the derivation cohort was 44 ± 11 years, with 80% female and 74% in New York Heart Association class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 ± 11 with a wide distribution (1.6 to 57.5 WU/m 2 ). Allometric relations were observed between PVRI and RV fractional area change (R 2  = 0.53, p adaptation. In right heart parameters, RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95% confidence interval 1.37 to 2.75, p adaptability indices provided stronger discrimination of outcome than simple RV adaptation metrics in either the derivation or the validation cohort. In conclusion, allometric modeling enables quantification of the proportionality of RV load adaptation but offers small incremental prognostic value to RV end-systolic dimension in PAH. Copyright © 2017 Elsevier Inc. All rights reserved.

Arterial hypertension in women at different ages

OpenAIRE

Pacheco-Romero, José

2011-01-01

Hypertension is associated to co-morbidities such as diabetes mellitus, coronary artery disease, stroke, peripheral vascular disease, chronic renal failure, entities that decrease life span. Peruvians suffer from arterial hypertension with characteristics similar to those of the general population. Early detection and treatment of hypertension should benefit them with years of quality of life. The occurrence of arterial hypertension in women from childhood through menopause, including reprodu...

Rehabilitation in patients with pulmonary arterial hypertension.

Science.gov (United States)

Keusch, Stephan; Turk, Alexander; Saxer, Stéphanie; Ehlken, Nicola; Grunig, Ekkehard; Ulrich, Silvia; On Behalf Of The Swiss Society Of Pulmonary Hypertension

2017-07-11

Exertional dyspnoea is a leading symptom in patients with pulmonary arterial hypertension (PAH). Patients suffering from PAH report poor quality of life, have skeletal muscle dysfunction and in the absence of advanced medical therapy deteriorate progressively due to right heart failure which can lead to death. For decades, patients with PAH were advised to avoid exercise in fear of exacerbated right heart failure. Recently, it has been shown that a highly supervised rehabilitation programme in expert centres leads to significant improvements in symptoms, quality of life, exercise capacity and may even enhance haemodynamics in selected stable patients treated with advanced regimens of PAH-targeted drugs. As a consequence of these promising results, pulmonary rehabilitation performed in an expert centre has been included in recent guidelines. The underlying mechanisms are not completely understood, but positive effects can be measured in different organ systems such as skeletal muscles, the cardiopulmonary system and immune system (inflammation), and also on the psychological level. Thus, improvements in 6-minute walking distance (6MWD), peak oxygen uptake (VO2 peak), muscle strength and muscle endurance, as well as physical and mental quality of life scores (SF-36 questionnaire) have been shown. Different training protocols have been used. Essential are qualified patient selection in expert centres, a low workload endurance and dumbbell (weight lifting) training avoiding strenuous exercise and exhaustion, thorough patient education and close supervision by experts especially during the first weeks. Adverse events may occur (e.g., pre-/syncope, arrhythmia, respiratory infections). PAH patients tend to overestimate their physical capacity, not perceiving their own limits properly, which makes education and expert advice even more important as exercise training can also worsen the right heart failure. Therefore, a core issue of the multidisciplinary rehabilitation is

Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension.

Science.gov (United States)

Edwards, Adrienne L; Gunningham, Sarah P; Clare, Geoffrey C; Hayman, Matthew W; Smith, Mark; Frampton, Christopher M A; Robinson, Bridget A; Troughton, Richard W; Beckert, Lutz E L

2013-11-01

Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown. This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival. Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

[Definition and classification of pulmonary arterial hypertension].

Science.gov (United States)

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'.

THE PREVALENCE AND FEATURES OF ULTRASOUND PULMONARY ARTERIAL HYPERTENSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

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Guşetu Gabriel,

2015-02-01

Full Text Available Background. Connective tissue diseases (CTDs are an important cause of pulmonary arterial hypertension (PAH, which leads to worsening of prognosis especially in patients with systemic lupus erythematosus (SLE and systemic sclerosis. However, studies on the prevalence of PAH in SLE scarce; our aim is to assess the prevalence and characteristics of PAH in a series of SLE inpatients of a tertiary Romanian SLE Center. Methods. The study included 54 consecutive SLE patients with a regular follow-up at the Department of Rheumatology Cluj-Napoca. The patients underwent physical examination and transthoracic echocardiography to evaluate systolic pulmonary arterial pressure (sPAP, left ventricular performance, and the presence of valvular heart disease. Patient characteristic, cumulative organ damage and laboratory were retrieved by medical chart review. Results. Within the cohort (mean age 43.7 ± 12.4 years, 90.8% women, median duration of disease 7 years, 11 (20.3% patients were diagnosed with PAH, the majority of which (63.6% were categorized as mild. The mean sPAP value was 45.54 mmHg and was associated with a history thromboembolic events (p=0.0067, antiphospholipid antibodies (aPL (p=0.039, and cumulative organ damage (p=0.001. No significant associations with disease duration, Raynaud’s phenomenon, pericardial effusion or SLE-associated autoantibodies were found. Left ventricular diastolic dysfunction (LVDD occurred more frequent in patients with PAH (p=0.008. Conclusion. Patients with SLE have an increased prevalence of PAH, which is generally asymptomatic and of low severity. PAH is associated with cumulative organ damage, LVDD, and antiphospholipid syndrome (likely reflecting secondary PAH to pulmonary embolism, but not with the disease duration and the Raynaud’s phenomenon or SLE specific autoantibodies.

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

Science.gov (United States)

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.

Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005

NARCIS (Netherlands)

van Loon, Rosa Laura E.; Roofthooft, Marcus T. R.; Hillege, Hans L.; ten Harkel, Arend D. J.; van Osch-Gevers, Magdalena; Delhaas, Tammo; Kapusta, Livia; Strengers, Jan L. M.; Rammeloo, Lukas; Clur, Sally-Ann B.; Mulder, Barbara J. M.; Berger, Rolf M. F.

2011-01-01

Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Two

Pulmonary hypertension and thyrotoxicosis | Conradie | Journal of ...

African Journals Online (AJOL)

Thyrotoxicosis is listed as a cause of pulmonary arterial hypertension (PAH). The aetiopathogenesis remains largely uncertain, but an autoimmune mechanism has been postulated, among others. In this setting, other causes of PAH need to be actively sought and excluded prior to attributing it to the thyrotoxicosis.

Arterial hypertension in cirrhosis: arterial compliance, volume distribution, and central haemodynamics

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Fuglsang, S; Bendtsen, F

2006-01-01

, was significantly better in hypertensive cirrhotics than in their normotensive counterparts (pportal pressure was similar (HVPG 13 v 15 mm Hg; NS). AC was significantly lower and normal in the arterial hypertensive cirrhotic group (1.07 v 1.39 mm Hg/ml; p...BACKGROUND AND AIMS: Arterial hypertension is a common disorder. Hyperkinetic circulation and reduced effective volaemia are central elements in the haemodynamic dysfunction in cirrhosis. The aim of the present study was to investigate whether cirrhotic patients with arterial hypertension...... are normokinetic and normovolaemic or whether they reveal the same circulatory dysfunction as their normotensive counterparts. MATERIAL AND METHODS: Thirty three patients with arterial hypertension were identified among 648 patients with cirrhosis: 14 in Child class A, 12 in class B, and seven in class C. Controls...

Prevalence of breast arterial calcification in hypertensive patients

International Nuclear Information System (INIS)

Cetin, M.; Cetin, R.; Tamer, N.

2004-01-01

AIM: To determine the age-specific prevalence of breast arterial calcifications in patients with systemic hypertension. METHODS: The mammograms and patient records of 2406 women who underwent screening or diagnostic mammography were reviewed retrospectively. Mammograms were evaluated for the presence of arterial calcification and results were coded. Hypertension was defined as use of anti-hypertensive agents and diabetes was defined as use of oral hypoglycaemic agents or insulin. RESULTS: The prevalence of breast arterial calcification among hypertensives (17.6%) was lower than among diabetics (25.4%). The prevalence in the non-diabetic, non-hypertensive group was lowest (7.3%). The prevalence increased with age in all three groups. The highest prevalence was found in diabetics older than 60 years (81.8%). Breast arterial calcification was not found among women younger than 40 years. CONCLUSION: Breast arterial calcification is associated with hypertension and prevalence increases with age. Breast arterial calcification on mammograms may indicate unsuspected hypertension especially in non-diabetic patients

Bronchial compression in an infant with isolated secundum atrial septal defect associated with severe pulmonary arterial hypertension

Directory of Open Access Journals (Sweden)

Sung-Hee Park

2012-08-01

Full Text Available Symptomatic pulmonary arterial hypertension (PAH in patients with isolated atrial septal defect (ASD is rare during infancy. We report a case of isolated ASD with severe PAH in an infant who developed airway obstruction as cardiomegaly progressed. The patient presented with recurrent severe respiratory insufficiency and failure to thrive before the repair of the ASD. Echocardiography confirmed volume overload on the right side of heart and severe PAH (tricuspid regurgitation [TR] with a peak pressure gradient of 55 to 60 mmHg. The chest radiographs demonstrated severe collapse of both lung fields, and a computed tomography scan showed narrowing of the main bronchus because of an intrinsic cause, as well as a dilated pulmonary artery compressing the main bronchus on the left and the intermediate bronchus on the right. ASD patch closure was performed when the infant was 8 months old. After the repair of the ASD, echocardiography showed improvement of PAH (TR with a peak pressure gradient of 22 to 26 mmHg, and the patient has not developed recurrent respiratory infections while showing successful catch-up growth. In infants with symptomatic isolated ASD, especially in those with respiratory insufficiency associated with severe PAH, extrinsic airway compression should be considered. Correcting any congenital heart diseases in these patients may improve their symptoms.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life.

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Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M L; Singh, Jitendra; Kumar, Vivek

2018-01-01

Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Comparison of Brain Natriuretic Peptide Levels to Simultaneously Obtained Right Heart Hemodynamics in Stable Outpatients with Pulmonary Arterial Hypertension.

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Helgeson, Scott A; Imam, J Saadi; Moss, John E; Hodge, David O; Burger, Charles D

2018-05-01

Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP ( p = 0.021) and mPAP ( p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement ( p = 0.03). An increased BNP level was an independent predictor of mortality ( p right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH.

Arterial hypertension and chronic liver disease

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Møller, S

2005-01-01

, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt : Does the beneficial effect persist?

NARCIS (Netherlands)

van Loon, Rosa Laura E.; Hoendermis, Elke S.; Duffels, Marielle G. J.; Vonk-Noordegraaf, Anton; Mulder, Barbara J. M.; Hillege, Hans L.; Berger, Rolf M. F.

2007-01-01

BACKGROUND: Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce. METHODS: We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months),

Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: Does the beneficial effect persist?

NARCIS (Netherlands)

van Loon, Rosa Laura E.; Hoendermis, Elke S.; Duffels, Marielle G. J.; Vonk-Noordegraaf, Anton; Mulder, Barbara J. M.; Hillege, Hans L.; Berger, Rolf M. F.

2007-01-01

Background Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce. Methods We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months),

Novel biomarkers for risk stratification in pulmonary arterial hypertension

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Thomas Zelniker

2015-10-01

Full Text Available Risk stratification in pulmonary arterial hypertension (PAH is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT, pro-atrial natriuretic peptide (proANP, growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4% patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR 1.91, hsTnT (HR 1.41, echocardiographic right ventricular impairment (HR 1.30 and 6-min walk test (HR 0.97 per 10 m remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

[Arterial hypertension secondary to endocrine disorders].

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Minder, Anna; Zulewski, Henryk

2015-06-01

Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: an initiative to close the care gap.

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McLaughlin, Vallerie V; Langer, Anatoly; Tan, Mary; Clements, Philip J; Oudiz, Ronald J; Tapson, Victor F; Channick, Richard N; Rubin, Lewis J

2013-02-01

The Pulmonary Arterial Hypertension-Quality Enhancement Research Initiative (PAHQuERI) was created to help clinicians to implement a guidelines-based approach to the diagnosis and management of pulmonary arterial hypertension (PAH). Patients with PAH represent a heterogeneous population, and physician evaluation and treatment paradigms may vary considerably. Using an electronic data management system, participating physicians recorded data on diagnostic workup, disease management, and outcomes of patients with PAH. Queries were generated automatically following each follow-up visit if the tests recommended by the American College of Chest Physicians (ACCP) were not performed at least once. Of 791 patients enrolled in PAH-QuERI, 77% were women; 64% received a diagnosis . 3 months prior to enrollment; 9% were in New York Heart Association functional class I, 39% in II, 48% in III, and 5% in IV; and the median age was 55 years (interquartile range, 45-66 years). At enrollment, all ACCP-recommended tests had been performed in only 6% of patients. The automated program generated 1,530 reminders for 642 patients (81%) with validated enrollment data. The proportion of recommended tests performed was 91% for CBC count, 91% for liver function test, 50% for connective tissue disease screen, 29% for HIV screen, 88% for chest radiograph, 82% for ECG, 97% for two-dimensional echocardiogram, 83% for pulmonary function tests, 41% for oximetry, 57% for ventilation/perfusion scan, 79% for 6-min walk distance, and 90% for right-sided heart catheterization. Regarding management, 78% of patients were on disease specific therapy, and the use of these therapies tended to increase with the functional disability of the patient. One hundred seventy patients were taking calcium channel blockers, 91 specifically for PAH. Only six of 91 patients (7%) who received calcium channel blockers specifically for PAH had met the current guideline for acute vasoreactivity. When comparing reported

EMERGENCY STATES IN ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

M. A. Gurevich

2014-01-01

Full Text Available The article describes in detail potential emergency states in patients with different stages of arterial hypertension with special attention to diagnosis and rational management of hypertensive crisis. Differentiated approach to management of different forms of hypertensive crisis is specified.

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

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

2015-11-01

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

Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

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Sada, Yoshiharu; Dohi, Yoshihiro; Uga, Sayuri; Higashi, Akifumi; Kinoshita, Hiroki; Kihara, Yasuki

2016-08-01

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

Increased bleeding risk during percutaneous coronary interventions by arterial hypertension.

Science.gov (United States)

Ndrepepa, Gjin; Groha, Philipp; Lahmann, Anna L; Lohaus, Raphaela; Cassese, Salvatore; Schulz-Schüpke, Stefanie; Kufner, Sebastian; Mayer, Katharina; Bernlochner, Isabell; Byrne, Robert A; Fusaro, Massimiliano; Laugwitz, Karl-Ludwig; Schunkert, Heribert; Kastrati, Adnan

2016-08-01

We aimed to assess the association between arterial hypertension and bleeding in patients undergoing percutaneous coronary intervention (PCI). The impact of arterial hypertension on bleeding risk of patients with coronary artery disease undergoing PCI is unknown. This study included 14,180 patients who underwent PCI. Bleeding was defined using the Bleeding Academic Research Consortium (BARC) criteria. Arterial hypertension was defined as treatment with antihypertensive drugs or a systolic blood pressure >140 mm Hg and/or diastolic blood pressure value >90 mm Hg documented on at least 2 occasions. The primary outcome was bleeding rate within 30 days of PCI. Overall, 11,066 patients (78.0%) had arterial hypertension. Bleeding events occurred in 1,232 patients with arterial hypertension and 278 patients without arterial hypertension (11.1% vs 8.9%; odds ratio [OR] = 1.28, 95% confidence interval [CI] 1.11-1.46, P arterial hypertension and 175 patients without arterial hypertension (6.6% vs 5.6%: OR = 1.19 [1.01-1.41], P = 0.049). Non-access-site bleeding occurred in 502 patients with and 103 patients without arterial hypertension (4.5% vs 3.3%; OR = 1.39 [1.12-1.72], P = 0.003). After adjustment, arterial hypertension was significantly associated with any bleeding (adjusted OR = 1.41 [1.19-1.67], P arterial hypertension increased the risk of non-access-site bleeding (P = 0.002), whereas systolic blood pressure at the time of PCI increased the risk of access site bleeding (P = 0.018). Arterial hypertension is associated with increased risk of bleeding during PCI procedures. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

International Nuclear Information System (INIS)

Ye, Lusi; Jiang, Ying; Zuo, Xiaoxia

2015-01-01

Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.

Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

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Ye, Lusi [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325015 (China); Jiang, Ying [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Zuo, Xiaoxia, E-mail: susanzuo@hotmail.com [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China)

2015-11-06

Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.

[The leptin concentration in patients with primary arterial hypertension].

Science.gov (United States)

Jołda-Mydłowska, Beata; Przewłocka-Kosmala, Monika; Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2006-01-01

Leptin seems to play a role in the pathogenesis of arterial hypertension by activation of the sympathetic nervous system, influencing water - electrolyte balance and vascular remodeling. It is not known whether leptin is a factor participating in the pathogenesis of primary arterial hypertension or its higher concentration in patients with arterial hypertension reflects only the presence of other factors leading to increased blood pressure. The aim of the study was to try to estimate the leptin participation in the development of the arterial hypertension, to evaluate the concentration of leptin in blood serum of patients with mild, moderate and severe arterial hypertension and to determine the relationships between the observed leptin concentration, arterial hypertension degree according to WHO criteria and body mass. The investigations were performed on 74 untreated patients aged 19-74 years (mean 47 +/- 12 years ). In this group there were 33 women aged 35-74 years (mean 51 +/- 10 years) and 41 men aged 19-73 years (mean 45 +/- 14 years). The mild arterial hypertension was observed in 24 patients, moderate hypertension in 34 patients and severe hypertension in 16. The obesity, identified when BMI was equal or higher than 30 kg/m2, was observed in 4 patients with mild hypertension, in 9 with moderate hypertension and in 6 with severe hypertension. All patients had normal renal function. The leptin concentration was determined by the radioimmunological method using the Human Leptin RIA Kit by LINCO Research, Inc. (Cat# HL-81 K). The analysis of the obtained results was performed using Statistica for Windows PL.V5.0. The concentration of leptin in patients with mild hypertension was 3.61 +/- 2.22 ng/ml, in patients with moderate hypertension was 12.65 +/- 8.48 and in patients with severe hypertension 33.51 +/- 28.45 ng/ml. The concentration of leptin in obese patients was 24.83 +/- 26.60 and in patients without obesity was 10.57 +/- 11.99 ng/ml. 1. In patients with

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

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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

Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline.

Science.gov (United States)

Zheng, Hai-Kuo; Zhao, Jun-Han; Yan, Yi; Lian, Tian-Yu; Ye, Jue; Wang, Xiao-Jian; Wang, Zhe; Jing, Zhi-Cheng; He, Yang-Yang; Yang, Ping

2018-05-11

Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. A single subcutaneous injection of monocrotaline (MCT) (60 mg kg - 1 ) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.

Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring

DEFF Research Database (Denmark)

Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle

2016-01-01

High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compa......, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension.......High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We...... compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents...

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

Science.gov (United States)

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.

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

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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.

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

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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 (pendurance 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; pendurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.

Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension.

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Xu, Weiling; Erzurum, Serpil C

2011-01-01

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary hemodynamics and excessive growth and dysfunction of the endothelial cells that line the arteries in PAH lungs. Establishment of methods for culture of pulmonary artery endothelial cells from PAH lungs has provided the groundwork for mechanistic translational studies that confirm and extend findings from model systems and spontaneous pulmonary hypertension in animals. Endothelial cell hyperproliferation, survival, and alterations of biochemical-metabolic pathways are the unifying endothelial pathobiology of the disease. The hyperproliferative and apoptosis-resistant phenotype of PAH endothelial cells is dependent upon the activation of signal transducer and activator of transcription (STAT) 3, a fundamental regulator of cell survival and angiogenesis. Animal models of PAH, patients with PAH, and human PAH endothelial cells produce low nitric oxide (NO). In association with the low level of NO, endothelial cells have reduced mitochondrial numbers and cellular respiration, which is associated with more than a threefold increase in glycolysis for energy production. The shift to glycolysis is related to low levels of NO and likely to the pathologic expression of the prosurvival and proangiogenic signal transducer, hypoxia-inducible factor (HIF)-1, and the reduced mitochondrial antioxidant manganese superoxide dismutase (MnSOD). In this article, we review the phenotypic changes of the endothelium in PAH and the biochemical mechanisms accounting for the proliferative, glycolytic, and strongly proangiogenic phenotype of these dysfunctional cells, which consequently foster the panvascular progressive pulmonary remodeling in PAH. © 2011 American Physiological Society.

Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models.

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Amsallem, Myriam; Sweatt, Andrew J; Aymami, Marie C; Kuznetsova, Tatiana; Selej, Mona; Lu, HongQuan; Mercier, Olaf; Fadel, Elie; Schnittger, Ingela; McConnell, Michael V; Rabinovitch, Marlene; Zamanian, Roham T; Haddad, Francois

2017-06-01

Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension. From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (χ 2 , 62.2; P right heart metrics, RVESRI demonstrated the best test-retest characteristics. RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension. © 2017 American Heart Association, Inc.

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

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de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

2016-09-01

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

Value of MR phase-contrast flow measurements for functional assessment of pulmonary arterial hypertension

International Nuclear Information System (INIS)

Ley, Sebastian; Mereles, Derliz; Gruenig, Ekkehard; Puderbach, Michael; Schoeck, Helena; Eichinger, Monika; Ley-Zaporozhan, Julia; Fink, Christian; Kauczor, Hans-Ulrich

2007-01-01

Goals of our study were to compare the pulmonary hemodynamics between healthy volunteers and patients with pulmonary arterial hypertension (PAH) and correlate MR flow measurements with echocardiography. Twenty-five patients with PAH and 25 volunteers were examined at 1.5 T. Phase-contrast flow measurements were performed in the ascending aorta and pulmonary trunk, resulting in the following parameters: peak velocity (cm/s), average blood flow (l/min), time to peak velocity (ms), velocity rise gradient and pulmonary distensibility (cm 2 ). The bronchosystemic shunt was calculated. In PAH patients transthoracic echocardiography and right-heart catheterization (RHC) served as the gold standard. In comparison to volunteers, the PAH patients showed significantly reduced pulmonary velocities (P = 0.002), blood flow (P = 0.002) and pulmonary distensibility (P = 0.008). In patients, the time to peak velocity was shorter (P<0.001), and the velocity rise gradient was steeper (P = 0.002) than in volunteers. While in volunteers the peak velocity in the aorta was reached earlier, it was the reverse in patients. Patients showed a significant bronchosystemic shunt (P = 0.01). No meaningful correlation was found between MRI measurements and echocardiography or RHC. MRI is a feasible technique for the differentiation between PAH and volunteers. Further studies have to be conducted for the absolute calculation of pressure estimates. (orig.)

Cerivastatin Nano-Liposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.

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Lee, Young; Pai, S Balakrishna; Bellamkonda, Ravi V; Thompson, David H; Singh, Jaipal

2018-04-25

In this study, we have investigated nano-liposome as an approach to tailor the pharmacology of cerivastatin as a disease modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98±27 nm were generated by thin film and freeze-thaw process. The nano-liposomes demonstrated sustained drug release kinetics in vitro and inhibited proliferation of pulmonary artery smooth muscle cells with significantly less cellular cytotoxicity as compared to free cerivastatin. When delivered by inhalation to a rat model of monocrotalin induced PAH, cerivastatin significantly reduced pulmonary artery pressure from 55.13±9.82 mmHg to 35.56±6.59 mmHg (P < 0.001) and diminished pulmonary artery wall thickening. Echocardiography showed that cerivastatin significantly reduced right ventricle thickening (0.34±0.02 cm monocrotalin vs. 0.26±0.02 cm cerivastatin; P < 0.001) and increased pulmonary artery acceleration time (13.98±1.14 ms monocrotalin vs. 21.07±2.80 ms cerivastatin; P < 0.001). Nano-liposomal cerivastatin was equally effective or slightly better than cerivastatin in reducing pulmonary artery pressure (67.06±13.64 mmHg monocrotalin; 46.31±7.64 mmHg cerivastatin vs. 37.32±9.50 mmHg liposomal cerivastatin) and improving parameters of right ventricular function as measured by increasing pulmonary artery acceleration time (24.68±3.92 ms monocrotalin; 32.59±6.10 ms cerivastatin vs. 34.96±7.51 ms liposomal cerivastatin). More importantly, the rate and magnitude of toxic cerivastatin metabolite lactone generation from the intratracheally administered nano-liposomes was significantly lower as compared to intravenously administered free cerivastatin. These studies show that nano-liposome encapsulation improved in vitro and in vivo pharmacological and safety profile of cerivastatin and may represent a safer approach as a disease modifying therapy for PAH. The American Society for Pharmacology and Experimental

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

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

2017-05-31

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

Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery.

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Brunner, Nathan; de Jesus Perez, Vinicio A; Richter, Alice; Haddad, François; Denault, André; Rojas, Vanessa; Yuan, Ke; Orcholski, Mark; Liao, Xiaobo

2014-03-01

Pulmonary hypertensive crisis is an important cause of morbidity and mortality in patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) who require cardiac surgery. At present, prevention and management of perioperative pulmonary hypertensive crisis is aimed at optimizing cardiopulmonary interactions by targeting prostacyclin, endothelin, and nitric oxide signaling pathways within the pulmonary circulation with various pharmacological agents. This review is aimed at familiarizing the practitioner with the current pharmacological treatment for dealing with perioperative pulmonary hypertensive crisis in PAH-CHD patients. Given the life-threatening complications associated with pulmonary hypertensive crisis, proper perioperative planning can help anticipate cardiopulmonary complications and optimize surgical outcomes in this patient population.

Recent advances in the management of pulmonary arterial hypertension [version 1; referees: 2 approved

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Halley Tsai

2016-11-01

Full Text Available Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH, a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan, and oral prostanoids (treprostinil and selexipag. Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.

Reproducibility of peak filling and peak emptying rate determined by cardiovascular magnetic resonance imaging for assessment of biventricular systolic and diastolic dysfunction in patients with pulmonary arterial hypertension

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Göransson, Christoffer; Vejlstrup, Niels; Carlsen, Jørn

2018-01-01

Right ventricular (RV) and left ventricular (LV) diastolic stiffness may be independent contributors to disease progression in pulmonary arterial hypertension (PAH). The aims of this study are to assess reproducibility of peak emptying rate (PER) and early diastolic peak filling rate (PFR) for both...

Human pentraxin 3 (PTX3 as a novel biomarker for the diagnosis of pulmonary arterial hypertension.

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Yuichi Tamura

Full Text Available BACKGROUND: Although inflammation is an important feature of pulmonary arterial hypertension (PAH, the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3, a local inflammatory marker, would be a useful biomarker for detecting PAH. METHODS: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH, and six with congenital heart disease, 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP and C-reactive protein (CRP were also determined. RESULTS: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001. Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001. There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866 is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%. CONCLUSION: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance.

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Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Suzuki, Nahoko; Murakami, Masahiro

2017-12-01

To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study.

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Hascoet, Sebastien; Fournier, Emmanuelle; Jaïs, Xavier; Le Gloan, Lauriane; Dauphin, Claire; Houeijeh, Ali; Godart, Francois; Iriart, Xavier; Richard, Adelaïde; Radojevic, Jelena; Amedro, Pascal; Bosser, Gilles; Souletie, Nathalie; Bernard, Yvette; Moceri, Pamela; Bouvaist, Hélène; Mauran, Pierre; Barre, Elise; Basquin, Adeline; Karsenty, Clement; Bonnet, Damien; Iserin, Laurence; Sitbon, Olivier; Petit, Jérôme; Fadel, Elie; Humbert, Marc; Ladouceur, Magalie

2017-05-01

The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. To investigate outcomes in patients with ES, and their relationship with PAH-SDT. Retrospective, observational, nationwide, multicentre cohort study. We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE5I]) 46.7%; dual therapy (ERA+PDE5I) 40.9%; triple therapy (ERA+PDE5I+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009). Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

β2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats.

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Hisashi Nagai

Full Text Available In sleep apnea syndrome (SAS, intermittent hypoxia (IH induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV during sleep, which presumably contribute to pulmonary arterial hypertension (PAH. However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4-21% O2 for 8 h/d for 6 w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β(1, 2-blocker augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and endothelial nitric oxide synthase (eNOS were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway.

The impact and financial burden of pulmonary arterial hypertension on patients and caregivers: results from a national survey.

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Zhai, Zhenguo; Zhou, Xia; Zhang, Shuai; Xie, Wanmu; Wan, Jun; Kuang, Tuguang; Yang, Yuanhua; Huang, Huan; Wang, Chen

2017-09-01

Pulmonary arterial hypertension (PAH) is a chronic progressive devastating disease. Symptom burden might impair health-related quality of life of patients. Furthermore, treatment on this disease brings significant financial burden to patients' families. Both physiological and psychological symptoms have been reported, but limited evidence regarding the impact of PAH on patients and caregivers exists, especially the emotional issues and their association with patients' health quality. The main purpose of this study was to describe the impact of PAH on patients and their caregivers in a Chinese population.This large-scale national survey enrolled 174 participants to complete questionnaires using face-to-face semistructured interviews.PAH influenced all aspects of patients' lives including daily activities, work, emotions, and personal relationships. Both patients and caregivers reported a major impact on family finances and on their work. The majority of patients had feelings of isolation. A lack of public understanding about PAH contributes to social isolation. Most patients and caregivers would like to get information regarding PAH doctors and patient organization contacts to obtain support.This survey-based report provides information regarding the way and extent to which PAH impacts both patients and their caregivers and provides some means for comparison with non-Chinese populations. It is important for physicians and the community to offer more support and information for PAH patients and their families.

Mortality in Pulmonary Arterial Hypertension Patients Treated with Continuous Prostanoids.

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Bartolome, S D; Sood, N; Shah, T S; Styrvoky, K; Torres, F T; Chin, K M

2018-04-18

Parenteral prostanoids are considered the treatment of choice for patients with severe pulmonary arterial hypertension (PAH). Prognostic studies for patients treated in the modern era are limited. In this retrospective cohort study, patients initiating IV epoprostenol or IV or SC treprostinil therapy for PAH from 2007-2016 at UT Southwestern, Dallas, TX and Ohio State University, Columbus, OH were included. Transplant-free survival was assessed from the time of IV/SC initiation and from the time of first follow-up. The utility of traditional prognostic measures was assessed using categories (lower, intermediate, higher risk) recommended in the 2015 ESC/ERS guidelines for functional class (FC), six-minute walk distance (6MWD), brain natriuretic peptide (BNP) or N-terminal BNP (NT-proBNP) level and hemodynamic results. Patients with group 1 PAH receiving IV epoprostenol (N=132), IV treprostinil (N=25) or SC treprostinil (N=38) were included. Survival from IV/SC prostanoid initiation was 84%, 77% and 67% at one, two and three years. Follow-up assessment was performed after a minimum of 90 days therapy (mean 356±247 days) in 163 patients. After treatment with an IV/SC prostanoid, better FC, 6MWD, BNP / NT-proBNP and SVO2 but not cardiac index associated with survival, as did the total number of lower-risk and higher-risk findings. Having zero lower risk or two or more higher risk findings was associated with particularly poor outcomes. In PAH patients receiving treatment with a parenteral prostanoid, survival associates significantly with the number of guideline recommended lower-risk and higher-risk criteria achieved at first follow-up. Copyright © 2018. Published by Elsevier Inc.

The safety of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension: Protocol for a systemic review and network meta-analysis.

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Gu, Zhi-Chun; Zhang, Yi-Jing; Pan, Mang-Mang; Zhang, Chi; Liu, Xiao-Yan; Wei, An-Hua; Su, Ying-Jie

2018-03-01

Pulmonary arterial hypertension (PAH) is a progressive disease and ultimately leads to right heart failure. Endothelin receptor antagonists (ERAs) have been demonstrated to significantly improve prognosis in PAH. However, ERAs-induced side effects can result in poor patient tolerance. Thus, we aim to evaluate current safety evidence of ERAs in PAH. An electronic search will be performed for randomized controlled trials (RCTs) that reported the interested safety data (abnormal liver function, peripheral edema, and anemia) of ERAs in PAH. Risk ratios (RRs) with their confidence intervals (CIs) and the surface under the cumulative ranking curve (SUCRA) will be calculated using a network analysis. This study will provide the safety evidence of ERAs in PAH by combining the results of individual studies based on direct- and network comparison, and to rank ERAs in the evidence network. The results will supplement missing evidence of head-to-head comparisons between different ERAs and guide both clinical decision-making and future research.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

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Rose, Jonathan A; Wanner, Nicholas; Cheong, Hoi I; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Relationship of left ventricular, elastic and muscular arteries remodeling in patients with uncontrolled arterial hypertension

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S. Ya. Dotsenko

2013-04-01

Full Text Available Introduction. Uncontrolled hypertension is observed in 65-92% of hypertensive patients. It plays an important role in the development of adverse cardiovascular events and survival, which depend on subclinical target organ damage. There are reports on the relationship between ineffective hypertension control and left ventricular (LV hypertrophy or large arteries stiffness. However, the nature of the remodeling in uncontrolled hypertension remains poorly understood. Objective: to study the character and relationship of left ventricular and arterial remodeling depending on effectiveness of hypertension control. Design and method. We performed a study of 363 hypertensive patients (160 men and 203 women aged 50,8 ± 1,2 years without comorbidities, which were divided into 3 groups according to the effectiveness of blood pressure (BP control: 160 patients with controlled hypertension, 142 patients with uncontrolled hypertension and 61 patients with resistant hypertension. Uncontrolled BP based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Remodeling indexes of left ventricular, elastic (common carotid and muscular (brachial artery were evaluated by the ultrasonic method. The severity and character of diastolic dysfunction, hypertrophy, types of remodeling and stiffness were assessed. Statistical processing of the results was performed using Student's t criterion and Pearson correlation analysis. Results and discussion. According to the results of the study, uncontrolled hypertension affected the development of subclinical cardiovascular lesions negatively. Thus, LV hypertrophy was detected more frequently in the third group (91,8% in resistant hypertension versus 46,8% in controlled hypertension, p<0,05. Differences in LV geometry with increasing of concentric remodeling types were also observed more frequently in the third group, where concentric remodeling and concentric hypertrophy types were founded in 14,8% and 59

3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats.

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Lan, Tao-Hua; Chen, Xiao-Ling; Wu, Yun-Shan; Qiu, Hui-Liang; Li, Jun-Zhe; Ruan, Xin-Min; Xu, Dan-Ping; Lin, Dong-Qun

2018-06-15

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

2017-01-01

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

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension

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Palevsky Harold I

2005-04-01

Full Text Available Abstract Background The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. Methods 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. Results For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each. Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09. All telephone tests were completed within one hour. Conclusion Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

Transition from Ambrisentan to Bosentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study

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Su-Gang Gong

2018-01-01

Full Text Available Background and objective: Two endothelin receptor antagonists (ETRAs, bosentan and ambrisentan, are approved for patients with pulmonary arterial hypertension (PAH. However, there is little information about the transition strategy between these two ETRAs. We aimed to evaluate the safety and efficacy from ambrisentan to bosentan. Methods: Twenty PAH patients were enrolled into the single-center, open-labelled prospective study. Echocardiogram, WHO functional class (WHO-FC, 6-minute walking distance (6MWD, right heart catheterization, and hemotology were collected. After receiving oral 5 mg ambrisentan daily initially for one year, the patients were divided into two arms: eight patients switched to bosentan, while the remaining 12 patients continued ambrisentan. Characteristics at baseline, 1-and 2-year follow-up points were compared. Results: There were no significant differences in echocardiogram, WHO-FC, hemodynamics, demographics and liver function at baseline, 1-and 2-year points in both arms. 6MWD in bosentan group was significantly shorter at baseline. But there were no significant differences of 6MWD at 1- and 2-year points. Conclusions: It is safe for stable PAH patients to transition from ambrisentan to bosentan without hemodynamic or hematologic deterioration.

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

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

2016-01-01

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

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

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Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

2010-01-01

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

Risk factors for pulmonary arterial hypertension in patients with tuberculosis-destroyed lungs and their clinical characteristics compared with patients with chronic obstructive pulmonary disease.

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Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2017-01-01

There are limited data on pulmonary arterial hypertension (PAH) in patients with tuberculosis-destroyed lung (TDL), a sequela of pulmonary tuberculosis. We identified the risk factors for PAH and their effects on acute exacerbation and mortality in patients with TDL, as well as the clinical differences in patients with chronic obstructive pulmonary disease (COPD) and PAH. A retrospective cohort study was conducted from 2010 through 2015 in a municipal referral hospital in South Korea. PAH was defined when echocardiographic pulmonary arterial pressure (PAP) was >40 mmHg. The clinical features and course of TDL patients with or without PAH were evaluated and differences between patients with COPD and PAH were analyzed. Among the 195 patients with TDL, echocardiographic data were available in 53 patients, and their mean PAP was 50.72±23.99 mmHg. The PAH group (n=37) had a smaller lung volume (forced vital capacity % predicted, 51.55% vs 72.37%, P <0.001) and more extensively destroyed lungs (3.27 lobes vs 2 lobes, P <0.001) than those in the non-PAH group (n=16). A higher PAP was significantly correlated with a higher frequency of acute exacerbation ( r =0.32, P =0.02). Multivariate analyses did not reveal any significant risk factors contributing to PAH in patients with TDL. Compared to COPD patients with PAH, TDL patients with PAH have smaller lung volume but a less severe airflow limitation. Tricuspid regurgitation and a D-shaped left ventricle during diastole were more frequently observed in TDL patients. The risk of exacerbation was not different between patients with PAH in COPD and TDL. PAH in patients with TDL was associated with severity of lung destruction but risk of exacerbation and mortality did not significantly differ between patients with PAH and without PAH.

Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

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Agafonova, I G; Bogdanovich, R N; Kolosova, N G

2015-12-01

Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation.

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Hopper, Rachel K; Feinstein, Jeffrey A; Manning, Melanie A; Benitz, William; Hudgins, Louanne

2015-04-01

Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. The RAF1 gene encodes Raf-1 kinase, part of the Ras/mitogen-activated kinase (MAPK) signaling pathway, which has been linked to the development of PAH. This specific mutation has been associated with dephosphorylation of a critical serine residue and constitutive activation of the Raf-1 kinase. These two cases suggest that abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation. © 2015 Wiley Periodicals, Inc.

Adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR into French-Canadian and English-Canadian

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Donna Coffin

2008-01-01

Full Text Available BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR is the first disease-specific instrument for assessing patient-reported symptoms, functioning and quality of life (QoL in pulmonary arterial hypertension (PAH.

3-Bromopyruvate reverses hypoxia-induced pulmonary arterial hypertension through inhibiting glycolysis: In vitro and in vivo studies.

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Chen, Fangzheng; Wang, Heng; Lai, Jiadan; Cai, Shujing; Yuan, Linbo

2018-05-04

Pulmonary arterial smooth muscle cell (PASMC) proliferation is vital to pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) pathogenesis, and inhibiting PASMC metabolism could serve as a new possible therapy to reverse the process. 3-Bromopyruvate (3-BrPA) is an effective glycolysis inhibitor with its effect in PAH remains unclear. Our study aims to assess the therapeutic effect of 3-BrPA in PAH rats and investigate the possible mechanism of 3-BrPA in PASMC proliferation and apoptosis. 27 healthy SD rats were grouped and treated with hypoxia/normoxia and administration of 3-BrPA/physiological saline. Mean pulmonary artery pressure (mPAP) and cardiac output (CO) were measured and pulmonary vascular resistance (PVR) was calculated. Right ventricular hypertrophy index (RVHI) was calculated to evaluate the right ventricular hypertrophy degree. The percentage of medial wall area (WA%) and medial wall thickness (WT%) were measured by image analysis. PASMCs groups received hypoxia/normoxia treatments and 3-BrPA/physiological saline. PASMC proliferation and migration were respectively detected by CCK-8 and cell wound scratch assay. Hexokinase II (HK-2) expression and lactate level were respectively measured by Western Blotting and lactate test kit to detect glycolysis. mPAP, PVR, PVHI, WA% and WT% in rats increased after the hypoxia treatment, but were lower compared to rats received 3-BrPA in hypoxia environment. HK-2 expression, lactate concentration, OD value and scratch areas in PASMCs increased after the hypoxia treatment, but were decreased after the administration of 3-BrPA. 3-BrPA can inhibit PASMC proliferation and migration by inhibiting glycolysis, and is effective in reversing the vascular remodeling in hypoxia-induced PAH rats. Copyright © 2017. Published by Elsevier B.V.

Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

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Gao XF

2017-05-01

Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

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2012-01-01

Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

Validation of an arterial tortuosity measure with application to hypertension collection of clinical hypertensive patients.

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Diedrich, Karl T; Roberts, John A; Schmidt, Richard H; Kang, Chang-Ki; Cho, Zang-Hee; Parker, Dennis L

2011-10-18

Hypertension may increase tortuosity or twistedness of arteries. We applied a centerline extraction algorithm and tortuosity metric to magnetic resonance angiography (MRA) brain images to quantitatively measure the tortuosity of arterial vessel centerlines. The most commonly used arterial tortuosity measure is the distance factor metric (DFM). This study tested a DFM based measurement's ability to detect increases in arterial tortuosity of hypertensives using existing images. Existing images presented challenges such as different resolutions which may affect the tortuosity measurement, different depths of the area imaged, and different artifacts of imaging that require filtering. The stability and accuracy of alternative centerline algorithms was validated in numerically generated models and test brain MRA data. Existing images were gathered from previous studies and clinical medical systems by manually reading electronic medical records to identify hypertensives and negatives. Images of different resolutions were interpolated to similar resolutions. Arterial tortuosity in MRA images was measured from a DFM curve and tested on numerically generated models as well as MRA images from two hypertensive and three negative control populations. Comparisons were made between different resolutions, different filters, hypertensives versus negatives, and different negative controls. In tests using numerical models of a simple helix, the measured tortuosity increased as expected with more tightly coiled helices. Interpolation reduced resolution-dependent differences in measured tortuosity. The Korean hypertensive population had significantly higher arterial tortuosity than its corresponding negative control population across multiple arteries. In addition one negative control population of different ethnicity had significantly less arterial tortuosity than the other two. Tortuosity can be compared between images of different resolutions by interpolating from lower to higher

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

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Cemşit Karakurt

2014-09-01

Full Text Available Background: Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. Aims: The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs-C reactive protein (hs-CRP levels in children with severe pulmonary arterial hypertension (PAH secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Study Design: Cross sectional study. Methods: After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Results: Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43 in the PAH group (group 1 and 0.40±0.72 (0.07-3.45 in group 2. There was a statistically significant difference between the two groups (p<0.01. Serum hs-CRP levels

The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models.

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Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Berger, Rolf M F

2013-07-01

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the pathogenesis of PAH and neointimal development is largely unknown. After three decades of PAH pathobiology research the focus has shifted from vasoconstriction towards a mechanism of cancer-like angioproliferation. In this concept the role of disturbed blood flow is seen as an important trigger in the development of vascular remodeling. For instance, in PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and PAH development. Still, questions remain about the exact role of these blood flow characteristics in disease progression. PAH animal models are important for obtaining insight in new pathobiological processes and therapeutical targets. However, as for any preclinical model the pathophysiological mechanism and clinical course has to be comparable to the human disease that it mimics. This means that animal models mimicking human PAH ideally are characterized by: a hit recognized in human disease (e.g., altered pulmonary blood flow), specific vascular remodeling resembling human neointimal lesions, and disease progression that leads to right ventriclular dysfunction and death. A review that underlines the current knowledge of PAH due to disturbed flow is still lacking. In this review we will summarize the current knowledge obtained from PAH animal models associated with disturbed pulmonary blood flow and address questions for future treatment strategies for PAH.

[Screening of pulmonary hypertension in a Spanish cohort of patients with systemic sclerosis].

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García Hernández, Francisco José; Castillo Palma, María Jesús; Montero Mateos, Enrique; González León, Rocío; López Haldón, José Eduardo; Sánchez Román, Julio

2016-01-01

Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc. PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE>35 mmHg were evaluated per protocol to confirm diagnosis and type of PH. PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P<.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19). Prevalence of PAH in SSc was high and supports the implementation of a regular screening program. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

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Xiang-Rong Zuo

Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

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Lei Yu

2017-05-01

Full Text Available Background/Objectives: The polyphenol resveratrol (Rev has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH. The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1 in apoptosis of pulmonary artery smooth muscle cells (PASMCs. Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT was identified by confocal microscopy. Right ventricular systolic pressure (RVSP was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced

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

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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.

Arterial stiffening precedes systolic hypertension in diet-induced obesity.

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Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

2013-12-01

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

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Jonathan A Rose

Full Text Available Pulmonary arterial hypertension (PAH is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Pathophysiological Features of Endogenous Intoxication in Pregnant Women with Arterial Hypertension

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N. V. Kabanova

2008-01-01

Full Text Available Objective: to determine the nature and specific features of development of endogenous intoxication in pregnant women with arterial hypertension. Subjects and materials. Humoral extracellular fluid volume regulation, partial renal functions, placental hormonal function, membranous lipid peroxidation activity, antiradical defense, the parameters of central hemodynamics, endogenous intoxication, and a biochemical coagulogram were studied and differential blood count with the leukocytic ratio indices was estimated in 172 pregnant females with arterial hypertension and 54 healthy pregnant ones in the third trimester. The statistical package «Stadia» was applied. Results. Arterial hypertension caused by pregnancy was ascertained to involve pathogenetically different types: low-, normal-, and high-renin ones. In pregnant women with arterial hypertension, the general pathogenetic homeostatic changes were placental hormonal imbalance, activated membranous lipid peroxidation, impaired lymph outflow, sodium and water retention, hepatic and renal failure, and endogenous intoxication. Conclusion. Placental ischemia appearing as placental hormonal imbalance (extrarenal pressor system was accompanied by a compensatory humoral response: arterial hypertension and metabolic disturbances. Changes in medium-weight molecule 280, leukocytic intoxication index, erythrocytic sorption capacity, and Paramecium test, by confirming the presence of endogenous intoxication in pregnant females with arterial hypertension, were caused by a type of arterial hypertension (by the hemodynamic profile and the type of impaired partial renal functions. Key words: pregnancy, arterial hypertension, endogenous intoxication.

The flavonoid quercetin reverses pulmonary hypertension in rats.

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Daniel Morales-Cano

Full Text Available Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

ESSENTIAL ARTERIAL HYPERTENSION AND RISK FACTORS ASSOCIATED WITH HYPERTENSIVE NEPHROPATHY

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Boban Milojković

2014-12-01

Full Text Available Arterial hypertension is a major risk factor that predisposes to cardiovascular disorders and is responsible for most of the morbidity and mortality in patients. Hypertension is closely associated with the kidney, because kidney disease can be both the cause and consequence of increased blood pressure. Elevation of blood pressure is a strong independent risk factor for hypertensive nephropathy and development of ESRD. The pathogenesis of ischemic hypertensive nephropathy (IHN is multifactoral, and in addition to blood pressure other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include obesity, smoking, male gender and other still unknown risk factors. The aim of this paper was to analyse the association between essential arterial hypertension and renal hypertensive disease and prevalence of other atherosclerotic risk factors in patients with developed hypertensive renal disease. In this prospective cross sectional study 283 patients of both genders with diagnosed essential hypertension and hypertensive renal disease were analysed. The anamnestic data related to age, duration of hypertension, history of smoking, presence of hypertensive retinopathy, hypertrophy of the left chamber and data about previous renal diseases were collected through conversation and medical documentation. The clinical examination comprise determination of blood pressure, body mass index (BMI, lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, serum urea and creatinine, urine, albumin and protein concentration. The total number of 283 patients (185 males and 98 females with HN was analyzed. The analysis revealed significantly higher proportion of males aged over 60 years with IHN. The mean age of examined hypertensive patients with IHN is 62.6±8.8 years with duration of hypertension 19.8±5.9 years. All examined patients had hypertensive retinopathy and

Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension.

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Potus, François; Ruffenach, Grégoire; Dahou, Abdellaziz; Thebault, Christophe; Breuils-Bonnet, Sandra; Tremblay, Ève; Nadeau, Valérie; Paradis, Renée; Graydon, Colin; Wong, Ryan; Johnson, Ian; Paulin, Roxane; Lajoie, Annie C; Perron, Jean; Charbonneau, Eric; Joubert, Philippe; Pibarot, Philippe; Michelakis, Evangelos D; Provencher, Steeve; Bonnet, Sébastien

2015-09-08

Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, the underlying mechanisms resulting in the failed RV in PAH remain unknown. There is growing evidence that angiogenesis and microRNAs are involved in PAH-associated RV failure. We hypothesized that microRNA-126 (miR-126) downregulation decreases microvessel density and promotes the transition from a compensated to a decompensated RV in PAH. We studied RV free wall tissues from humans with normal RV (n=17), those with compensated RV hypertrophy (n=8), and patients with PAH with decompensated RV failure (n=14). Compared with RV tissues from patients with compensated RV hypertrophy, patients with decompensated RV failure had decreased miR-126 expression (quantitative reverse transcription-polymerase chain reaction; P<0.01) and capillary density (CD31(+) immunofluorescence; P<0.001), whereas left ventricular tissues were not affected. miR-126 downregulation was associated with increased Sprouty-related EVH1 domain-containing protein 1 (SPRED-1), leading to decreased activation of RAF (phosphorylated RAF/RAF) and mitogen-activated protein kinase (MAPK); (phosphorylated MAPK/MAPK), thus inhibiting the vascular endothelial growth factor pathway. In vitro, Matrigel assay showed that miR-126 upregulation increased angiogenesis of primary cultured endothelial cells from patients with decompensated RV failure. Furthermore, in vivo miR-126 upregulation (mimic intravenous injection) improved cardiac vascular density and function of monocrotaline-induced PAH animals. RV failure in PAH is associated with a specific molecular signature within the RV, contributing to a decrease in RV vascular density and promoting the progression to RV failure. More importantly, miR-126 upregulation in the RV improves microvessel density and RV function in experimental PAH. © 2015 American Heart Association, Inc.

Micrococcus-associated central venous catheter infection in patients with pulmonary arterial hypertension.

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Oudiz, Ronald J; Widlitz, Allison; Beckmann, X Joy; Camanga, Daisy; Alfie, Jose; Brundage, Bruce H; Barst, Robyn J

2004-07-01

To determine the incidence of catheter-related infection in patients with pulmonary arterial hypertension (PAH) receiving epoprostenol (EPO), and to note an etiologic role for Micrococcus spp, which is rarely reported as a pathogen in the medical literature. Observational study. Two PAH specialty treatment centers, Harbor-UCLA Medical Center (Torrance, CA), and the College of Physicians and Surgeons, Columbia University (New York, NY). A total of 192 patients with PAH receiving continuous therapy with IV EPO. From 1987 to 2000, 192 patients with PAH received infusions of EPO via central venous catheter. Catheter care included regular dressing changes with dry gauze using a sterile procedure, without the use of flushes. Patients were asked to report on known infections and treatments, and symptoms. All infections were verified by a telephone call to the patient, care provider, and microbiology laboratory whenever possible. There were 335,285 catheter days (mean +/- SD, 1,325 +/- 974 catheter days). There were 88 clinical catheter infections with 51 blood culture-positive infections, necessitating catheter removal in 38 instances. The following pathogens were isolated: Staphylococcus aureus (25); Micrococcus spp (14); mixed flora (3); coagulase-negative Staphylococcus spp (2); Corynebacterium spp (2); Serratia marcessens (1); Enterobacter spp (1); Pseudomonas aeruginosa (1); enterococci (1); and unidentified Gram-positive cocci (1). The catheter infection rate was 0.26 per 1,000 catheter days. The use of long-term therapy with continuous EPO appears to be associated with a low incidence of catheter-related infections. Micrococcus spp were the second most common etiologic agent. Caregivers managing patients with PAH must be aware of the risk of catheter infection, as it may contribute to the morbidity and mortality associated with the use of EPO. When isolated, Micrococcus spp should not be viewed as a contaminant, but rather as a true pathogen that may require

Cost-utility and budget impact analysis of drug treatments in pulmonary arterial hypertension associated with congenital heart diseases in Thailand.

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Thongsri, Watsamon; Bussabawalai, Thanaporn; Leelahavarong, Pattara; Wanitkun, Suthep; Durongpisitkul, Kritvikrom; Chaikledkaew, Usa; Teerawattananon, Yot

2016-08-01

This study aims to compare the lifetime costs and health outcomes of both first-line and sequential combination treatments with standard treatment for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) patients. A cost-utility analysis was performed using a Markov model based on a societal perspective. One-way and probabilistic sensitivity analyses were performed to investigate the effect of parameter uncertainty. As first-line treatments, both beraprost (incremental cost-effectiveness ratio (ICER) = 192,752 and 201,308 Thai baht (THB) per quality-adjusted life year (QALY) gained) and sildenafil (ICER = 249,770 and 226,802 THB per QALY gained) seemed cost-effective for PAH-CHD patients aged ≤30 years in functional classes II and III, respectively, while no treatment was cost-effective for the sequential combination therapy. Sildenafil should be included in the National Drug List of Essential Medicines as the first-line treatment for PAH-CHD, and its price per dose should be negotiated to be reduced by 43-57%.

Prognostic factors in pediatric pulmonary arterial hypertension: A systematic review and meta-analysis.

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Ploegstra, Mark-Jan; Zijlstra, Willemijn M H; Douwes, Johannes M; Hillege, Hans L; Berger, Rolf M F

2015-04-01

Despite the introduction of targeted therapies in pediatric pulmonary arterial hypertension (PAH), prognosis remains poor. For the definition of treatment strategies and guidelines, there is a high need for an evidence-based recapitulation of prognostic factors. The aim of this study was to identify and evaluate prognostic factors in pediatric PAH by a systematic review of the literature and to summarize the prognostic value of currently reported prognostic factors using meta-analysis. Medline, EMBASE and Cochrane Library were searched on April 1st 2014 to identify original studies that described predictors of mortality or lung-transplantation exclusively in children with PAH. 1053 citations were identified, of which 25 were included for further analysis. Hazard ratios (HR) and 95% confidence intervals were extracted from the papers. For variables studied in at least three non-overlapping cohorts, a combined HR was calculated using random-effects meta-analysis. WHO functional class (WHO-FC, HR 2.7), (N-terminal pro-) brain natriuretic peptide ([NT-pro]BNP, HR 3.2), mean right atrial pressure (mRAP, HR 1.1), cardiac index (HR 0.7), indexed pulmonary vascular resistance (PVRi, HR 1.3) and acute vasodilator response (HR 0.3) were identified as significant prognostic factors (p ≤ 0.001). This systematic review combined with separate meta-analyses shows that WHO-FC, (NT-pro)BNP, mRAP, PVRi, cardiac index and acute vasodilator response are consistently reported prognostic factors for outcome in pediatric PAH. These variables are useful clinical tools to assess prognosis and should be incorporated in treatment strategies and guidelines for children with PAH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pediatric pulmonary hypertension in the Netherlands: Epidemiology and characterization during the period 1991 to 2005.

NARCIS (Netherlands)

R.L.E. van Loon (Rosa Laura); M.T.R. Roofthooft (Marcus); H.L. Hillege (Hans); A.D.J. ten Harkel (Arend); L. van Osch-Gevers (Lennie); T. Delhaas (Tammo); L. Kapusta (Livia); J.L.M. Strengers (Jan); L. Rammeloo (Lukas); S.A. Clur (Sally-Ann); B.J.M. Mulder (Barbara); R.M.F. Berger (Rolf)

2011-01-01

textabstractBACKGROUND-: Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of

Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005

NARCIS (Netherlands)

Loon, R.L. van; Roofthooft, M.T.; Hillege, H.L.; Harkel, A.D. Ten; Osch-Gevers, M. van; Delhaas, T.; Kapusta, L.; Strengers, J.L.; Rammeloo, L.; Clur, S.A.; Mulder, B.J.; Berger, R.M.

2011-01-01

Background- Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric

Pulmonary arterial hypertension secondary to chronic thromboemboli

International Nuclear Information System (INIS)

Crysikopoulos, H.; Forrest, J.V.; Olson, L.K.; Roberts, A.C.

1989-01-01

The authors report their experience in 150 patients with pulmonary arterial hypertension secondary to chronic pulmonary embolism (CPE). Plain film findings are variable, commonly nonspecific. Occasionally nonuniformity of pulmonary perfusion or truncation of central pulmonary arteries suggest CPE. Multiple, large, unmatched perfusion defects are the most common scintigraphic observations. CT can exclude conditions mimicking CPE, particularly fibrosing mediastinitis. Pulmonary arteriography depicts the location and distribution of emboli. CPE is becoming an increasingly important entity to recognize because of available surgical treatment. Thromboendarterectomy may improve functional status and survival. The diagnosis should be considered in any patient with pulmonary arterial hypertension

Oestrogen receptor alpha in pulmonary hypertension.

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Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

2015-05-01

Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

New therapies for arterial hypertension.

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Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

2016-03-01

Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.

MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

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Bi, Rui; Bao, Chunrong; Jiang, Lianyong; Liu, Hao; Yang, Yang; Mei, Ju; Ding, Fangbao, E-mail: dbcar126@126.com

2015-05-01

Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.

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

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Karoli N.A.

2013-06-01

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

Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: initial clinical experience.

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Esch, Jesse J; Shah, Pinak B; Cockrill, Barbara A; Farber, Harrison W; Landzberg, Michael J; Mehra, Mandeep R; Mullen, Mary P; Opotowsky, Alexander R; Waxman, Aaron B; Lock, James E; Marshall, Audrey C

2013-04-01

Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent-anchored by the vessel walls and surrounding tissue-serves as the shunt. TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Altered agonist-activated 86Rb+ efflux from arteries in canine renal hypertension

International Nuclear Information System (INIS)

Cox, R.H.; Bagshaw, R.J.

1989-01-01

Basal rate constants for 86 Rb+ efflux from renal arteries of renal hypertensive dogs were lower than those of control animals whereas no differences were found for coronary arteries. Norepinephrine produced parallel increases in efflux rate constants for hypertensive and control renal arteries, but serotonin produced smaller responses in hypertensive compared to control coronary arteries

[Arterial sequelae of pregnancy hypertension. Detection by carotid piezogram].

Science.gov (United States)

Meyer-Heine, A; Asquer, J C; Lagrue, G

1989-01-01

High blood pressure (HTA) is characterized by elevation of pression, but also by modifications of arterial pulse wave. Carotid piezograms were used to evaluate arterial pulse wave. Diastolic blood pressure is significantly correlated with dicrotic notch pressure. The duration of dicrotic notch is negatively correlated with arterial wall elasticity. Thus by carotid piezogram analysis one can determine the respective participation of arterial wall elasticity, peripheral resistance and cardiac factors in blood pressure elevation. Carotid piezograms were measured in 97 women (mean age 27, 8 y), with previous hypertensive pregnancy and apparently cured (mean blood pressure 122-74 mmHg at time of examination). 25 women only had normal piezogram drawing. Abnormalities similar to that of permanent hypertensive disease were observed in most cases. Dicrotic notch duration was significantly reduced and dicrotic notch pressure enhanced; in 34 women both of these abnormalities were present. In conclusion, among women previously hypertensive during pregnancy, even when blood pressure is returned to normal, abnormalities of arterial pulse wave may be present, suggesting that these women are prone to subsequent permanent hypertension.

Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study

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Spreeuwenberg Marieke D

2008-10-01

Full Text Available Abstract Background There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc. A decreasing transfer factor of the lung for CO (TLCO is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm and the capillary blood volume (Vc. The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. Methods Eleven SSc patients with PAH (SScPAH+, 13 SSc patients without PAH (SScPAH- and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned TLCO, these were adjusted for fibrosis score as assessed on HRCT. Results TLCO as percentage of predicted (% was lower in SScPAH+ than in SScPAH- (41 ± 7% vs. 63 ± 12%, p vs. 39 ± 12%, p Conclusion SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.

[Arterial hypertension due to altitude].

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Domej, Wolfgang; Trapp, Michael; Miggitsch, Eva Maria; Krakher, Tiziana; Riedlbauer, Rita; Roher, Peter; Schwaberger, Günther

2008-01-01

The behavior of blood pressure under hypoxic conditions depends on individual factors, altitude and duration of stay at altitude. While most humans are normotensive at higher altitudes, a few will react with moderate hypertension or hypotension. Excessive elevation of arterial blood pressure is not even to be expected below 4,000 m. Rather, several weeks' stay at higher altitude will decrease systolic and diastolic blood pressure at rest as well as during physical exertion. A high-altitude treatment for rehabilitation purposes at moderate altitude may be recommended for patients with cardio-circulatory disorders. Improvements can last several months even after returning to accustomed altitudes. Furthermore, endurance-trained hypertensive patients with pharmacologically controlled arterial blood pressure might be able to participate in mountain treks without additional health risk.

Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

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Q Joyce Han

Full Text Available Right ventricular (RV function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH. The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI to derive RV kinetic energy (KE work density and energy loss in the pulmonary artery (PA to better characterize RV work in PAH patients.4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA.PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007 as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001 throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction.This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

Science.gov (United States)

Han, Q Joyce; Witschey, Walter R T; Fang-Yen, Christopher M; Arkles, Jeffrey S; Barker, Alex J; Forfia, Paul R; Han, Yuchi

2015-01-01

Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

Right heart catheterisation: best practice and pitfalls in pulmonary hypertension

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Stephan Rosenkranz

2015-12-01

Full Text Available Right heart catheterisation (RHC plays a central role in identifying pulmonary hypertension (PH disorders, and is required to definitively diagnose pulmonary arterial hypertension (PAH. Despite widespread acceptance, there is a lack of guidance regarding the best practice for performing RHC in clinical practice. In order to ensure the correct evaluation of haemodynamic parameters directly measured or calculated from RHC, attention should be drawn to standardising procedures such as the position of the pressure transducer and catheter balloon inflation volume. Measurement of pulmonary arterial wedge pressure, in particular, is vulnerable to over- or under-wedging, which can give rise to false readings. In turn, errors in RHC measurement and data interpretation can complicate the differentiation of PAH from other PH disorders and lead to misdiagnosis. In addition to diagnosis, the role of RHC in conjunction with noninvasive tests is widening rapidly to encompass monitoring of treatment response and establishing prognosis of patients diagnosed with PAH. However, further standardisation of RHC is warranted to ensure optimal use in routine clinical practice.

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

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Makoto Sahara

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

Genetics of pulmonary hypertension in the clinic.

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Girerd, Barbara; Lau, Edmund; Montani, David; Humbert, Marc

2017-09-01

Heritable pulmonary arterial hypertension (PAH) is an autosomal dominant disease with incomplete penetrance because of mutations in bone morphogenetic protein receptor-II (BMPR2), activin A receptor type II-like kinase 1, endoglin, caveolin-1, potassium channel subfamily K, member 3, and T-box gene 4 genes. Heritable pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH) is an autosomal recessive disease because of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene. The 2015 european society of cardiology (ESC) and european respiratory society (ERS) pulmonary hypertension guidelines recommend genetic counselling and testing to adults and children with PAH or PVOD/PCH as well as in adult relatives at risk of carrying a predisposing mutation. In France, genetic counseling and testing are offered to all patients displaying sporadic or familial form of PAH or PVOD/PCH and to their relatives at high risk of carrying a predisposing mutation. Patients with a heritable form of PAH are younger at diagnosis with a worse hemodynamic and a dismal prognosis. Patients with a heritable form of PVOD/PCH are younger at diagnosis with a worse response to specific PAH therapies. A program to detect PAH in an early phase was offered to all asymptomatic BMPR2 mutation carriers, according to the 2015 ESC/ERS guidelines. Finally, preimplantation genetic diagnosis has been performed in families with a history of BMPR2 mutations. Genetic counseling and testing has to be implemented in pulmonary hypertension centers.

[Therapy-resistant and therapy-refractory arterial hypertension].

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Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Abnormal splenic artery diameter/hepatic artery diameter ratio in cirrhosis-induced portal hypertension

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Zeng, Dao-Bing; Dai, Chuan-Zhou; Lu, Shi-Chun; He, Ning; Wang, Wei; Li, Hong-Jun

2013-01-01

AIM: To determine an optimal cutoff value for abnormal splenic artery diameter/proper hepatic artery diameter (S/P) ratio in cirrhosis-induced portal hypertension. METHODS: Patients with cirrhosis and portal hypertension (n = 770) and healthy volunteers (n = 31) underwent volumetric computed tomography three-dimensional vascular reconstruction to measure the internal diameters of the splenic artery and proper hepatic artery to calculate the S/P ratio. The cutoff value for abnormal S/P ratio was determined using receiver operating characteristic curve analysis, and the prevalence of abnormal S/P ratio and associations between abnormal S/P ratio and major complications of portal hypertension were studied using logistic regression. RESULTS: The receiver operating characteristic analysis showed that the cutoff points for abnormal splenic artery internal diameter and S/P ratio were > 5.19 mm and > 1.40, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 74.2%, 45.2%, 97.1%, and 6.6%, respectively. The prevalence of an abnormal S/P ratio in the patients with cirrhosis and portal hypertension was 83.4%. Patients with a higher S/P ratio had a lower risk of developing ascites [odds ratio (OR) = 0.708, 95%CI: 0.508-0.986, P = 0.041] and a higher risk of developing esophageal and gastric varices (OR = 1.483, 95%CI: 1.010-2.175, P = 0.044) and forming collateral circulation (OR = 1.518, 95%CI: 1.033-2.230, P = 0.034). After splenectomy, the portal venous pressure and maximum and mean portal venous flow velocities were reduced, while the flow rate and maximum and minimum flow velocities of the hepatic artery were increased (P portal hypertension, and it can be used as an important marker of splanchnic hemodynamic disturbances. PMID:23483462

In vivo hypertensive arterial wall uptake of radiolabeled liposomes

International Nuclear Information System (INIS)

Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H.

1990-01-01

Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [111In]nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall

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

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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.

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

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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.

Directory of Open Access Journals (Sweden)

J K Mansoor

Full Text Available 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.

Elastin in large artery stiffness and hypertension

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Wagenseil, Jessica E.; Mecham, Robert P.

2012-01-01

Large artery stiffness, as measured by pulse wave velocity (PWV), is correlated with high blood pressure and may be a causative factor in essential hypertension. The extracellular matrix components, specifically the mix of elastin and collagen in the vessel wall, determine the passive mechanical properties of the large arteries. Elastin is organized into elastic fibers in the wall during arterial development in a complex process that requires spatial and temporal coordination of numerous proteins. The elastic fibers last the lifetime of the organism, but are subject to proteolytic degradation and chemical alterations that change their mechanical properties. This review discusses how alterations in the amount, assembly, organization or chemical properties of the elastic fibers affect arterial stiffness and blood pressure. Strategies for encouraging or reversing alterations to the elastic fibers are addressed. Methods for determining the efficacy of these strategies, by measuring elastin amounts and arterial stiffness, are summarized. Therapies that have a direct effect on arterial stiffness through alterations to the elastic fibers in the wall may be an effective treatment for essential hypertension. PMID:22290157

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

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Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the

Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension

NARCIS (Netherlands)

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

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

Studies on arterial stiffness and wave reflections in hypertension.

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Safar, Michel E; Levy, Bernard I

2015-01-01

Patho-physiological and pharmacological studies have consistently noticed that, with the exception of subjects with end-stage renal disease, total intravascular blood volume is not increased in patients with chronic hypertension. Because the mean circulatory pressure is enhanced in such subjects, it was postulated that the compliance of the cardiovascular system could be abnormally low in this particular population. This simple observation has influenced a great part of our experimental and clinical research directed toward subjects with hypertension and their relationship with the compliance of the vascular system. These works started between 1970 and 1980 by methodological investigations and validations followed by analysis of clinical situations that showed that venous and mostly arterial stiffness were significantly increased in hypertensive patients independently of blood pressure level. During the same time, we assessed the role of endothelium on the large arterial wall mechanical properties in normotensive and hypertensive rats. Thereafter more specific directions have been developed, affecting large arteries structure and function and arterial wall remodeling, including their consequences on central and peripheral hemodynamics. In parallel, epidemiological studies identified the pulsatile hemodynamic parameters as major independent predictors of cardiovascular risks. The consequences of these alterations on clinical pharmacology and therapeutics in hypertension are analyzed in detail. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Review of Clinical Trial Endpoints of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension and How They Relate to Patient Outcomes in the United States.

Science.gov (United States)

Divers, Christine; Platt, David; Wang, Edward; Lin, Jay; Lingohr-Smith, Melissa; Mathai, Stephen C

2017-01-01

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subgroups of pulmonary hypertension and are considered rare diseases. Understanding how endpoints of clinical trials (and patient registry studies) of patients with PAH and CTEPH are associated with patient outcomes is important in order to address the concerns of patients, health care providers, decision makers, and payers. The purpose of this review was to examine how endpoints used in clinical trials and patient registry studies are associated with outcomes of patients with PAH and CTEPH. A PubMed literature search was conducted to retrieve published studies, including randomized phase III clinical trials and observational studies, from years 2000 to May 2015 that evaluated the associations between change in 6-minute walking distance (6MWD), 6MWD thresholds, change in World Health Organization functional class (WHO-FC), and time to clinical worsening with outcomes of patients with PAH and CTEPH. Based on this review of published literature, a reduction in 6MWD as a criterion for PAH worsening, a deterioration in WHO-FC, and delay in the time to clinical worsening are clinically meaningful trial endpoints and are associated with outcomes of patients with PAH and CTEPH. Utilization and standardization of these endpoints will be useful for comparing interventions of clinical trials and therapies. Hospitalizations are frequent among patients with PAH and CTEPH, and total health care costs are high. From a U.S. payer perspective, clinical worsening is an important composite endpoint in that it includes hospitalization, which can be transformed into a preventative cost value associated with efficacious treatment of patients with PAH and CTEPH. In view of the greater number of medications available to treat PAH, the introduction of the first approved therapy to treat CTEPH, and the increasing use of combination pharmacotherapy, reliable prognostic markers of treatment

Increased arterial vascular tone during the night in patients with essential hypertension

DEFF Research Database (Denmark)

Scholze, A; Burkert, A; Mardanzai, K

2007-01-01

The time-dependent incidence of cardiovascular events points to an important role of chronobiology for arterial properties. To evaluate arterial properties in patients with essential hypertension, we assessed arterial vascular tone during sleep at night in patients with essential hypertension...... of systemic arterial vascular tone in patients with essential hypertension during the first half of the night compared to normotensive control subjects....... was significantly higher in 31 patients with essential hypertension compared to 30 normotensive control subjects (30.0+/-0.2 vs 28.8+/-0.2; P=0.001). In patients with essential hypertension, the reflective index significantly increased from 30.0+/-0.2 in the first half (from 2301 to 0230) to 30...

miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

Science.gov (United States)

Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

2018-05-02

■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension.

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Rosenthal, T; Bass, A; Grossman, E; Shani, M; Griffel, B; Adar, R

1987-09-01

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.

Transcatheter closure of large patent ductus arteriosus with severe pulmonary arterial hypertension in adults: immediate and two-year follow-up results.

Science.gov (United States)

Zhang, Cao-Jin; Huang, Yi-Gao; Huang, Xin-Sheng; Huang, Tao; Huang, Wen-Hui; Xia, Chun-Li; Mo, Yu-Jing

2012-11-01

Transcatheter closure of patent ductus arteriosus (PDA) is a well established procedure and an accepted treatment modality for small to moderate-sized PDA. This study aimed to evaluate the immediate and follow-up results of transcatheter closure of large PDAs with severe pulmonary arterial hypertension (PAH) in adults. After a complete hemodynamic evaluation differentiating from the reversibility of severe PAH, transcatheter closure of PDA was performed. Patients were followed up clinically and echocardiographically at 24 hours, 1 month, 3 months, 6 months, 12 months and 24 months after occlusion. Twenty-nine patients had successful occlusion, pulmonary artery pressure (PAP), left ventricular ejection fraction (LVEF) and fractional shortening (FS) significantly decreased immediately after occlusion ((106 ± 25) mmHg vs. (50 ± 14) mmHg, P closure, the signs and symptoms improved markedly in all 29 patients, and PDAs were completely closed and remained closed during the follow-up. Eighteen patients having different degrees of dyspnea were treated with angiotensin converting enzyme inhibitor (ACEI) and/or digoxin after occlusion. Nine patients whose pulmonary vascular resistence (PVR) > 6 Wood units accepted targeted PAH therapy. After 1 to 3 months of peroral drug therapy, their exercise tolerance improved from New York Heart Association (NYHA) class III-IV to NYHA class I. During follow-up, no latent arrhythmias were found, the left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular mass index (LVMI) and pulmonary artery systolic pressure (PASP) decreased significantly (P closure of large PDA with severe PAH is feasible, effective, and safe in adults. Significant left ventricular systolic changes may occur after closure of large PDA, and left ventricular function usually recovers within a few months.

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

Science.gov (United States)

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.

A disease looking for innovative drugs: The case of pulmonary arterial hypertension.

Science.gov (United States)

Joppi, Roberta; Gerardi, Chiara; Bertele', Vittorio; Garattini, Silvio

2018-05-25

Pulmonary arterial hypertension (PAH) is a life-threatening rare disease. Between 2001 and 2016 the European Medicines Agency (EMA) approved nine drugs to treat PAH. Considering the poor prognosis of patients with PAH it would be useful to understand whether the approved therapies can change the natural history of the disease. We assessed the therapeutic value and the quality of the evidence on medicines that have been authorized by the EMA in the 2000s. Information about drug approval was obtained from the EMA website and the European Public Assessment Reports. MedLine, Embase, and Cochrane databases were systematically searched for published randomized clinical trials and meta-analyses of the selected drugs and their combinations. At the time of approval no medicine had been proved to reduce mortality or slow the progression of the disease or to improve patients' quality of life. Recent meta-analyses concluded that, compared to placebo, active treatments reduced mortality but there was no conclusion on any preferred therapeutic option. Approvals of monotherapies in the absence of best evidence of their efficacy, have prompted the search for better efficacy of their combinations. Three meta-analyses found no advantage in survival from combinations as opposed to monotherapies. This model case confirms previous analyses that marketing authorizations granted in spite of low evidence of therapeutic efficacy not only expose patients to treatments with unknown benefit-risk profiles but also hamper post-marketing research aimed at filling the information gap. Copyright © 2018. Published by Elsevier B.V.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-06-15

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

Anxiety, Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH.

Science.gov (United States)

Pfeuffer, Elena; Krannich, Holger; Halank, Michael; Wilkens, Heinrike; Kolb, Philipp; Jany, Berthold; Held, Matthias

2017-12-01

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking. A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension. Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both "mental health" (p = 0.01) and "mental component summary score" (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO 2 levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups. While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH.

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

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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

Impact of Social Media on Prevention of Arterial Hypertension

OpenAIRE

Pushina, O.S.

2016-01-01

The results of the analysis of the impact of social media on the prevention of arterial hypertension are given. The current situation and the possibility of usage of social media for awareness, prevention and monitoring of public knowledge about arterial hypertension risk factors and healthy lifestyle, as well as the risks of penetration of social media in medicine is analyzed.

Renovascular hypertension and intrarenal artery aneurysms in a preschool child

International Nuclear Information System (INIS)

Hobbs, David J.; Barletta, Gina-Marie; Bunchman, Timothy E.; Mowry, Jeanne A.

2009-01-01

Renovascular hypertension from renal artery aneurysmal formation is a rare complication of fibromuscular dysplasia. Few data exist to direct the management of intrarenal artery aneurysms in pediatric patients. We report the presentation, diagnosis and management of renovascular hypertension and intrarenal aneurysmal disease in a preschool child. (orig.)

Renovascular hypertension and intrarenal artery aneurysms in a preschool child

Energy Technology Data Exchange (ETDEWEB)

Hobbs, David J.; Barletta, Gina-Marie; Bunchman, Timothy E. [Michigan State University College of Human Medicine, Grand Rapids, MI (United States); Helen DeVos Children' s Hospital, Pediatric Nephrology, Dialysis and Transplantation, Grand Rapids, MI (United States); Mowry, Jeanne A. [Oregon Health Sciences University, Pediatric Nephrology, Northwest Permanente, P.C. and Doernbecher Children' s Hospital, Portland, OR (United States)

2009-09-15

Renovascular hypertension from renal artery aneurysmal formation is a rare complication of fibromuscular dysplasia. Few data exist to direct the management of intrarenal artery aneurysms in pediatric patients. We report the presentation, diagnosis and management of renovascular hypertension and intrarenal aneurysmal disease in a preschool child. (orig.)

Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.

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Ito, Wulf D; Lund, Natalie; Sager, Hendrik; Becker, Wiebke; Wenzel, Ulrich

2015-01-01

Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth. We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP‑1) on collateral proliferation and macrophage accumulation in these models Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP‑1 only enhanced vascular proliferation in diabetic animals. These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.

Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.

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Rashid, Jahidur; Alobaida, Ahmad; Al-Hilal, Taslim A; Hammouda, Samia; McMurtry, Ivan F; Nozik-Grayck, Eva; Stenmark, Kurt R; Ahsan, Fakhrul

2018-06-28

Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosiglitazone can be repurposed as inhaled formulation for the treatment of PAH. We have tested this conjecture by preparing and optimizing poly(lactic-co-glycolic) acid (PLGA) based particles of rosiglitazone, assessing the drug particles for pulmonary absorption, investigating the efficacy of the plain versus particulate drug formulation in improving the respiratory hemodynamics in PAH animals, and finally studying the effect of the drug in regulating the molecular markers associated with PAH pathogenesis. The optimized particles were slightly porous and spherical, and released 87.9% ± 6.7% of the drug in 24 h. The elimination half-life of the drug formulated in PLGA particles was 2.5-fold greater than that of the plain drug administered via the same route at the same dose. The optimized formulation, given via the pulmonary route, produced pulmonary selective vasodilation in PAH animals, but oral rosiglitazone had no effect in pulmonary hemodynamics. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in the vasoconstriction and vasodilation of human pulmonary arterial smooth muscle cells. All in all, data generated using intact animal and cellular models point to the conclusion that PLGA particles of an antidiabetic drug can be used for the treatment of a different disease, PAH. Copyright © 2018 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

2016-01-01

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. (orig.)

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

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

2016-09-15

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

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

Science.gov (United States)

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

2018-02-27

The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH). Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction was assessed in 112 patients with PAH. Expression of nicotinic (α-7 nicotinic acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor) receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and lungs (n=7) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomly assigned to vehicle or treatment (both n=12). At the end of the study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological, and protein analyses. Patients with PAH with lower RV ejection fraction (<41%) had a significantly reduced heart rate recovery in comparison with patients with higher RV ejection fraction. In PAH RV samples, α-7 nicotinic acetylcholine receptor was increased and acetylcholinesterase activity was reduced versus controls. No difference in muscarinic acetylcholine type 2 receptor expression was observed. Chronic

Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension.

Directory of Open Access Journals (Sweden)

Richard B Rothman

Full Text Available The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/- mice were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/- mice. We postulated that: 1 Tph1(-/- mice express lower levels of pulmonary 5-HT transporter (SERT when compared to wild-type controls, and 2 Tph1(-/- mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR. Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/- mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/- mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/- mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized.

A convivência com a hipertensão arterial Coping with arterial hypertension

Directory of Open Access Journals (Sweden)

Edlene Loureiro Aceti Goes

2002-04-01

Full Text Available Estudo exploratório desenvolvido junto a 50 indivíduos hipertensos, com o objetivo de conhecer como eles percebem sua convivência com a hipertensão arterial. Os dados foram coletados através de entrevista semi-estruturada e os resultados revelaram que 40% deles se conheciam como hipertensos há mais de 10 anos e que 30% não apresentavam nenhum sintoma, por ocasião do diagnóstico. Grande parte percebe a hipertensão como uma doença que provoca preocupação, medo e revolta, sendo que mais da metade faz uma avaliação negativa de suas vidas após o diagnóstico. As mudanças sentidas com maior pesar estão relacionadas à limitação ao trabalho e a dificuldades financeirasThis is an exploratory study with 50 hypertensive individuals aiming to know how they perceive and cope with arterial hypertension. Data collected by an interview revealed that 40% of them have realized their hypertension conditions for over ten years and 30% had no symptom of the disease while diagnosis process. Most of them think that the arterial hypertension is a disease that requires concern, fear and revolt. The majority has a negative evaluation of life after the hypertension diagnosis. According to the hypertensive individuals, their largest difficulties are related to work limitation and financial problems

Fasudil and DETA NONOate, Loaded in a Peptide-Modified Liposomal Carrier, Slow PAH Progression upon Pulmonary Delivery.

Science.gov (United States)

Rashid, Jahidur; Nahar, Kamrun; Raut, Snehal; Keshavarz, Ali; Ahsan, Fakhrul

2018-05-07

We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long-acting nitric oxide donor, both loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC), in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified and CAR-modified liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia-induced PAH rats. We also conducted morphometric studies (degree of muscularization, arterial medial wall thickness, and collagen deposition) after treating the PAH rats with test and control formulations. When the rats were treated acutely and chronically, the reduction in mPAP was more pronounced in the liposomal formulation-treated rats than in plain drug-treated rats. CAR-modified liposomes were more selective in reducing mPAP than unmodified liposomes of the drugs. Both drugs, formulated in CAR-modified liposomes, reduced the degree of muscularization, medial arterial wall thickness, and collagen deposition more than the combination of plain drugs did. As seen with the in vivo data, CAR-modified liposomes of fasudil or DN increased the levels of the vasodilatory signaling molecule, cGMP, in the smooth muscle cells of PAH-afflicted human pulmonary arteries. Overall, fasudil and DN, formulated in liposomes, could be used as a combination therapy for a better management of PAH.

Arterial scleroproteins in atherosclerosis and hypertension (Experimental studies)

International Nuclear Information System (INIS)

Yurukova, Ts.; Georgiev, P.

1979-01-01

The authors studied the neosynthesis of fiber protein (scleroproteins) in the aorta of rats with genetic hypertension and with experimental atherosclerosis following application of 3 H-proline and 3 H-lysine and subsequent determination of radioactivity of the collagen and elastic fractions of the aortic wall. There was a great increase in incorporation of labelled collagen and elastin precursors in the aorta of hypertensive and atherosclerotic animals, in comparison with the control rats - a manifestation of incresed ''de novo'' synthesis of fiber proteins in rats with these arterial diseases. Furthermore, the increased collagenosis dominated over that of elastogenesis. The irregular activation of the biosynthesis of both scleroproteins in hypertensive rats and in rats with atherosclerosis caused remodelling of the macromolecular structure of the arterial wall with predominance of collagen over the remaining hypertension components and progression of atherosclerosis. (author) (author)

Safety and feasibility audit of a home-based drug-transitioning approach for patients with pulmonary arterial hypertension: an observational study.

Science.gov (United States)

Dawson, A; Reddecliffe, S; Coghlan, C; Schreiber, B E; Coghlan, J G

2018-04-01

Newer endothelin receptor antagonists (ERAs) used to treat patients with pulmonary arterial hypertension (PAH) are associated with fewer drug-drug interactions than bosentan and require less monitoring. This, combined with a pharmacokinetic basis for improved efficacy, means there may be a clinical rationale for changing therapies. However, this can be challenging and few data on its safety in patients with PAH are available. At the Royal Free Hospital in London, UK, home-based medication transitioning has been standard practice since 2009 to avoid unnecessary hospital visits for patients, unless there is a clinical imperative. In this audit of standard practice we evaluated the consequences of adopting such a strategy when transitioning PAH patients between ERA therapies. Using a Clinical Nurse Specialist-led, home-based transitioning strategy, 92 patients with PAH were transitioned from bosentan to macitentan or ambrisentan. Observational data were analysed retrospectively. The majority of patients were female with PAH associated with connective tissue disease and their ERA was changed in the hope of improving efficacy. The process was well tolerated with no adverse events associated with the process. Seventeen patients died during the study (macitentan, n = 5; ambrisentan, n = 12). None of the deaths was considered related to ERA treatment. The majority of patients remained clinically stable, based on WHO functional class and exercise capacity. An established home-based transitioning strategy can be adopted safely for patients with PAH changing ERA therapies. Most patients remained stable and the therapy change was well tolerated.

Norepinephrine release in arteries of spontaneously hypertensive rats

International Nuclear Information System (INIS)

Zsoter, T.T.; Wolchinsky, C.; Lawrin, M.; Sirko, S.

1982-01-01

The role of the sympathetic nervous system in arterial hypertension cannot be properly evaluated until it is known about the activity in the vessels themselves. In this study researchers investigated the effect of transmural stimulation on the tail artery - labelled in vitro with 3 H-norepinephrine - of 7-9 week old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKR). Electrical stimulation using two frequencies (2 and 10 Hz) resulted in significantly more 3 H overflow in vessels from SHR than from WKR. With 10 Hz stimulation the fractional release was also greater. Column chromatographic analysis of 3 H overflow revealed that transmural stimulation in arteries of SHR enhanced mainly the release of norepinephrine and not of its metabolites. Significantly, an increased release of 3 H-norepinephrine on stimulation was observed in SHR before the full development of hypertension suggesting that it might be a cause rather than a consequence of high blood pressure

Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

Science.gov (United States)

Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

2013-04-01

Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

Echocardiography in Arterial Hypertension.

Science.gov (United States)

de Simone, Giovanni; Mancusi, Costantino; Esposito, Roberta; De Luca, Nicola; Galderisi, Maurizio

2018-05-02

Hypertension is a condition characterized by pressure and/or volume overloads and echocardiography is helpful and feasible to understand hemodynamic mechanisms. Echocardiographic information is sometimes critical and susceptible of modifying decision making. In this review, we provide detailed descriptions of the parameters that can be derived from a standard transthoracic echocardiogram, including some more recent techniques. We will also explain how each parameter might have impact in the evaluation of the hypertensive patient and give indications on when to refer patients to echo-labs, which parameters are critical and which ones might be redundant, and how to use the information obtained in the report. Cardiac geometry, LV systolic and diastolic function, LV pump performance, output impedance and left atrial function are parameters that might be altered in arterial hypertension, but not necessarily doctors need the whole information for decision making. The critical measures are provided.

Arterial hypertension and associated factors in patients submitted to myocardial revascularization

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Flávia Cortez Colósimo

2015-04-01

Full Text Available OBJECTIVE To identify the prevalence of arterial hypertension and associated factors in patients submitted to myocardial revascularization. METHOD Cross-sectional study using the database of a hospital in São Paulo (SP, Brazil containing 3010 patients with coronary artery disease submitted to myocardial revascularization. A multiple logistic regression was performed to identify variables independently associated with hypertension (statistical significance: p1.3: (OR=1.37;CI:1.09-1.72. CONCLUSION A high prevalence of arterial hypertension and association with both non-modifiable and modifiable factors was observed.

[Comparison of arterial stiffness in non-hypertensive and hypertensive population of various age groups].

Science.gov (United States)

Zhang, Y J; Wu, S L; Li, H Y; Zhao, Q H; Ning, C H; Zhang, R Y; Yu, J X; Li, W; Chen, S H; Gao, J S

2018-01-24

Objective: To investigate the impact of blood pressure and age on arterial stiffness in general population. Methods: Participants who took part in 2010, 2012 and 2014 Kailuan health examination were included. Data of brachial ankle pulse wave velocity (baPWV) examination were analyzed. According to the WHO criteria of age, participants were divided into 3 age groups: 18-44 years group ( n= 11 608), 45-59 years group ( n= 12 757), above 60 years group ( n= 5 002). Participants were further divided into hypertension group and non-hypertension group according to the diagnostic criteria for hypertension (2010 Chinese guidelines for the managemengt of hypertension). Multiple linear regression analysis was used to analyze the association between systolic blood pressure (SBP) with baPWV in the total participants and then stratified by age groups. Multivariate logistic regression model was used to analyze the influence of blood pressure on arterial stiffness (baPWV≥1 400 cm/s) of various groups. Results: (1)The baseline characteristics of all participants: 35 350 participants completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV examination. 2 237 participants without blood pressure measurement values were excluded, 1 569 participants with history of peripheral artery disease were excluded, we also excluded 1 016 participants with history of cardiac-cerebral vascular disease. Data from 29 367 participants were analyzed. The age was (48.0±12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in various age groups: baPWV increased with aging. In non-hypertension population, baPWV in 18-44 years group, 45-59 years group, above 60 years group were as follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4 cm/s. BaPWV was significantly higher in hypertension group than non-hypertension group of respective age groups ( Page groups ( t -value

Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis

International Nuclear Information System (INIS)

Baggen, Vivan J.M.; Leiner, Tim; Habets, Jesse; Post, Marco C.; Dijk, Arie P. van; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Boersma, Eric

2016-01-01

To provide a comprehensive overview of all reported cardiac magnetic resonance (CMR) findings that predict clinical deterioration in pulmonary arterial hypertension (PAH). MEDLINE and EMBASE electronic databases were systematically searched for longitudinal studies published by April 2015 that reported associations between CMR findings and adverse clinical outcome in PAH. Studies were appraised using previously developed criteria for prognostic studies. Meta-analysis using random effect models was performed for CMR findings investigated by three or more studies. Eight papers (539 patients) investigating 21 different CMR findings were included. Meta-analysis showed that right ventricular (RV) ejection fraction was the strongest predictor of mortality in PAH (pooled HR 1.23 [95 % CI 1.07-1.41], p = 0.003) per 5 % decrease. In addition, RV end-diastolic volume index (pooled HR 1.06 [95 % CI 1.00-1.12], p = 0.049), RV end-systolic volume index (pooled HR 1.05 [95 % CI 1.01-1.09], p = 0.013) and left ventricular end-diastolic volume index (pooled HR 1.16 [95 % CI 1.00-1.34], p = 0.045) were of prognostic importance. RV and LV mass did not provide prognostic information (p = 0.852 and p = 0.983, respectively). This meta-analysis substantiates the clinical yield of specific CMR findings in the prognostication of PAH patients. Decreased RV ejection is the strongest and most well established predictor of mortality. (orig.)

Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Baggen, Vivan J.M. [AHMaZON Centre for Adult Congenital Heart Disease, University Medical Centre Utrecht, Radboud University Medical Centre Nijmegen and St. Antonius Hospital Nieuwegein, Department of Cardiology, Utrecht (Netherlands); Erasmus Medical Centre, Department of Cardiology, Rotterdam (Netherlands); Leiner, Tim; Habets, Jesse [University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Post, Marco C.; Dijk, Arie P. van; Sieswerda, Gertjan T. [AHMaZON Centre for Adult Congenital Heart Disease, University Medical Centre Utrecht, Radboud University Medical Centre Nijmegen and St. Antonius Hospital Nieuwegein, Department of Cardiology, Utrecht (Netherlands); Roos-Hesselink, Jolien W. [Erasmus Medical Centre, Department of Cardiology, Rotterdam (Netherlands); Boersma, Eric [Erasmus Medical Centre, Department of Cardiology, Rotterdam (Netherlands); Erasmus Medical Centre, Department of Clinical Epidemiology, Rotterdam (Netherlands)

2016-11-15

To provide a comprehensive overview of all reported cardiac magnetic resonance (CMR) findings that predict clinical deterioration in pulmonary arterial hypertension (PAH). MEDLINE and EMBASE electronic databases were systematically searched for longitudinal studies published by April 2015 that reported associations between CMR findings and adverse clinical outcome in PAH. Studies were appraised using previously developed criteria for prognostic studies. Meta-analysis using random effect models was performed for CMR findings investigated by three or more studies. Eight papers (539 patients) investigating 21 different CMR findings were included. Meta-analysis showed that right ventricular (RV) ejection fraction was the strongest predictor of mortality in PAH (pooled HR 1.23 [95 % CI 1.07-1.41], p = 0.003) per 5 % decrease. In addition, RV end-diastolic volume index (pooled HR 1.06 [95 % CI 1.00-1.12], p = 0.049), RV end-systolic volume index (pooled HR 1.05 [95 % CI 1.01-1.09], p = 0.013) and left ventricular end-diastolic volume index (pooled HR 1.16 [95 % CI 1.00-1.34], p = 0.045) were of prognostic importance. RV and LV mass did not provide prognostic information (p = 0.852 and p = 0.983, respectively). This meta-analysis substantiates the clinical yield of specific CMR findings in the prognostication of PAH patients. Decreased RV ejection is the strongest and most well established predictor of mortality. (orig.)

Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2.

Science.gov (United States)

Caruso, Paola; Dunmore, Benjamin J; Schlosser, Kenny; Schoors, Sandra; Dos Santos, Claudia; Perez-Iratxeta, Carol; Lavoie, Jessie R; Zhang, Hui; Long, Lu; Flockton, Amanda R; Frid, Maria G; Upton, Paul D; D'Alessandro, Angelo; Hadinnapola, Charaka; Kiskin, Fedir N; Taha, Mohamad; Hurst, Liam A; Ormiston, Mark L; Hata, Akiko; Stenmark, Kurt R; Carmeliet, Peter; Stewart, Duncan J; Morrell, Nicholas W

2017-12-19

Pulmonary arterial hypertension (PAH) is characterized by abnormal growth and enhanced glycolysis of pulmonary artery endothelial cells. However, the mechanisms underlying alterations in energy production have not been identified. Here, we examined the miRNA and proteomic profiles of blood outgrowth endothelial cells (BOECs) from patients with heritable PAH caused by mutations in the bone morphogenetic protein receptor type 2 ( BMPR2 ) gene and patients with idiopathic PAH to determine mechanisms underlying abnormal endothelial glycolysis. We hypothesized that in BOECs from patients with PAH, the downregulation of microRNA-124 (miR-124), determined with a tiered systems biology approach, is responsible for increased expression of the splicing factor PTBP1 (polypyrimidine tract binding protein), resulting in alternative splicing of pyruvate kinase muscle isoforms 1 and 2 (PKM1 and 2) and consequently increased PKM2 expression. We questioned whether this alternative regulation plays a critical role in the hyperglycolytic phenotype of PAH endothelial cells. Heritable PAH and idiopathic PAH BOECs recapitulated the metabolic abnormalities observed in pulmonary artery endothelial cells from patients with idiopathic PAH, confirming a switch from oxidative phosphorylation to aerobic glycolysis. Overexpression of miR-124 or siRNA silencing of PTPB1 restored normal proliferation and glycolysis in heritable PAH BOECs, corrected the dysregulation of glycolytic genes and lactate production, and partially restored mitochondrial respiration. BMPR2 knockdown in control BOECs reduced the expression of miR-124, increased PTPB1 , and enhanced glycolysis. Moreover, we observed reduced miR-124, increased PTPB1 and PKM2 expression, and significant dysregulation of glycolytic genes in the rat SUGEN-hypoxia model of severe PAH, characterized by reduced BMPR2 expression and endothelial hyperproliferation, supporting the relevance of this mechanism in vivo. Pulmonary vascular and

General characteristics affective disorders in arterial hypertension

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A. A. Tolmachov

2016-11-01

Full Text Available The author analyzes researches on the study of affective disorders in arterial hypertension (AH. It is noted that AH at the present stage is considered as one of the factors of cognitive dysfunction. The article emphasizes that the analysis of comorbid relations of depression and hypertension is hardly possible without the study of affective and cardiovascular disorders at the clinical level, taking into account their dynamic characteristics and key features of the course of depressive states in general. The author considers the features of the current: post-stroke depressions, nosogenic depressions of anxious and anxious-hypochondriacally types, anxiety-phobic disorders, comorbid panic disorders, protracted depression with traits of endoreactive dysthymia, hypochondriacal disorders, panic attacks, and the like in patients with arterial hypertension. Some features of affective disorders are revealed in patients with cardiovascular disorders. It is emphasized that the increase in the effectiveness of treatment of mental disorders in patients with hypertensive encephalopathy can be solved by improving the methods of early diagnosis, developing additional screening and monitoring diagnostic tools using it in an interdisciplinary approach.

Digital capillaroscopy as important tool for early diagnostics of arterial hypertension

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Gurfinkel, Yu. I.; Sasonko, M. L.; Priezzhev, A. V.

2015-03-01

The study is aimed to determine the digital capillaroscopy possibilities in early diagnostics of an arterial hypertension. A total of 123 adult persons were examined in the study. The first group consisted of 40 patients with prehypertension (BP 130-139/85-89 mm Hg). The second group included 36 patients with 1-2 stage of hypertension (mean systolic BP 152.7±12 mm Hg). Patients in both groups did not receive regular drug therapy. The group of volunteers (n=47) included healthy adults without signs of cardiovascular pathology. The capillary circulation was examined on the nailbed using the optical digital capillaroscope developed by the company "AET", Russia. Diameters of the arterial and venous segments, perivascular zone size, capillary blood velocity, the degree of arterial loops narrowing and the density of the capillary network were estimated. In patients with arterial hypertension and even in patients with prehypertension remodeling and rarefaction of capillaries and the expressed narrowing their arterial loops were manifested. The results of the study revealed the presence of abnormalities of microcirculation parameters in patients of both groups. The capillaries density in both groups of patients was significantly lower than in healthy persons. The significant narrowing of arterial loops was revealed in patients with both arterial hypertension and prehypertension, in comparison with healthy volunteers. Capillary blood velocity did not differ significantly between healthy volunteers group and the group of prehypertensive patients. However in patients with hypertension this parameter was significantly lower in comparison with control group.

Pulmonary arterial hypertension in congenital heart disease: Correlation of radiologic index with hemodynamic data

International Nuclear Information System (INIS)

Choi, Young Hi

1984-01-01

It is well known that pulmonary arterial hypertension in congenital heart disease is an important prognostic factor, as is pulmonary vascular resistance. So it is tempting to get certain radiologic index that could predict the presence and the degree of pulmonary arterial hypertension. A total of 152 cases of left to right shunt with pulmonary arterial hypertension and 50 cases of left to right shunt without pulmonary arterial hypertension is presented, in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between March 1981 and February 1983. Statistical analysis of plain radiography findings with the emphasis on the correction of radiologic index with the hemodynamic data. The results are as follows: 1. The incidence of pulmonary arterial hypertension is much less in arterial septal defect than other two disease groups of left to right shunt. 2. PA/T ratio correlates well with pulmonary arterial pressure (r=0.674), especially in mild pulmonary hypertension group. No correlation in moderate pulmonary hypertension group in significant level. 3. PA/T ratio is below 38 in total cases of normal control group and in 32 cases (21.0%) among 152 cases of pulmonary arterial hypertension group. 4. The average PA/T ratio in normal pressure group of left to right shunt is 35.3, which has no significant difference from that of normal control group. 5. The average CT ratio of pulmonary arterial hypertension group is 59.0, which is larger than 49.1 of normal control group. The CT ratio shows no correlation with the pulmonary arterial pressure in statistically significant level. 6. The higher the pulmonary arterial pressure, the larger the Rp/Rs value. The Rp/Rs in atrial septal defect is 0.193 in average, the lowest value in comparison with other two disease groups.

Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

DEFF Research Database (Denmark)

Henriksen, Jens Henrik; Møller, Søren

2005-01-01

, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

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Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Murakami, Masahiro

2017-05-01

To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

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

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

2015-07-01

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

Resting right ventricular function is associated with exercise performance in PAH, but not in CTEPH.

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Rehman, Michaela Beatrice; Howard, Luke S; Christiaens, Luc P; Gill, Dipender; Gibbs, J Simon R; Nihoyannopoulos, Petros

2018-02-01

To assess whether resting right ventricular (RV) function assessed by Global RV longitudinal strain (RVLS) and RV fractional area change (FAC) is associated with exercise performance in pulmonary arterial hypertension (PAH) and in chronic thromboembolic pulmonary hypertension (CTEPH). We prospectively recruited 46 consecutive patients with PAH and 42 patients with CTEPH who were referred for cardio-pulmonary exercise testing (CPET) and transthoracic echocardiography. Resting RV systolic function was assessed with RVLS and FAC. CPET parameters analyzed were percentage of predicted maximal oxygen consumption (VO2max) and the slope of ventilation against carbon dioxide production (VE/VCO2). Spearman correlation was performed between echocardiographic measurements and CPET measurements. In PAH, spearman correlation found an association between RVLS and VE/VCO2 (coefficient = 0.556, P PAH, resting RV function as assessed by FAC or RVLS is associated with exercise performance and could therefore make a significant contribution to non-invasive assessment in PAH patients. This association is not found in CTEPH, suggesting a disconnection between resting RV function and exercise performance, with implications for the use of exercise measurements as a prognostic marker and clinical/research endpoint in CTEPH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Hypertension, Diabetes Type II, and Their Association: Role of Arterial Stiffness.

Science.gov (United States)

Smulyan, Harold; Lieber, Ari; Safar, Michel E

2016-01-01

In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Arterial hypertension in children with hemolytic uremic syndrome after kidney transplantation.

Science.gov (United States)

Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

2015-08-01

The development of arterial hypertension after KTX is a well-known complication. HUS is a systemic disease associated with arterial hypertension during long-term follow-up. Our goal was to report on the severity of arterial hypertension after KTX in patients with typical and atypical HUS. We analyzed the course of 197 patients with HUS, of which 22 (n = 10 with typical HUS; n = 12 with atypical HUS) developed ESRF and received KTX as renal replacement therapy. We analyzed data from 1766 casual BP and 85 24-h ABPM measurements. In addition, we evaluated the used antihypertensive strategy. Comparison between the two patient groups revealed that patients with atypical HUS had significantly higher casual SBP-SDS and DBP-SDS values after KTX despite similar intensity of antihypertensive treatment. These data were supported by analysis of ABPM profiles showing comparable results for the interval 1-5 yr after KTX. Patients with atypical HUS had a greater severity of arterial hypertension despite similar treatment strategies and intensity of treatment. Our observation, even though in a small cohort, supports recent genetic studies showing arterial hypertension closely associated with HUS-causing mutations in patients with atypical HUS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Doppler sonographic evaluation of ophthalmic arterial flow pattern in hypertensive patients

International Nuclear Information System (INIS)

Ryu, Dae Sik; Kim, Young Goo

1994-01-01

To compare the Doppler velocity waveform pattern of ophthalmic artery of hypertensive patients with that of normotensive subjects. Doppler velocity waveform was obtained from ophthalmic artery in 45 hypertensive patients and 60 normotensive subjects. Both hypertensives and normotensive subjects were classified according to age into those younger than and those older than 45 years. Doppler indices(pulsatility index(PI), resistance index(RI), the first systolic peak/the second systolic peak(S1/S2), the first systolic peak/diastolic peak(S1/D)) measured in hypertensive patients were compared with normotensive subjects. Among the various doppler indices, only S1/S2 showed significant difference(P < 0.05) between the hypertensive patients and normotensive subjects younger than 45 years. Doppler velocity waveform of hypertensive patients older than 45 years showed no significant difference from that of normotensive subjects with corresponding age. Doppler velocity waveform of ophthalmic artery in hypertensive patients younger than 45 years shows pattern with S2 higher than that of normotensive subjects. High S2 component(reflective-wave) may represent increased vascular impedance due to vasococonstriction of retinal arterioles in hypertensive patients

Imaging nuclear medicine techniques for diagnostic evaluation of arterial hypertension

International Nuclear Information System (INIS)

Eisenberg, B.M.; Linss, G.

1989-01-01

Arterial hypertension may be caused by a malfunction of organs and in turn may lead to secondary organic lesions. Modern diagnostic nuclear medicine is applied for function studies in order to detect or exclude secondary hypertension and functional or perfusion disturbances due to hypertension, or to assess and follow up hemodynamic conditions and cardiac functions prior to and during therapy. The article presents a survey of imaging diagnostic nuclear medicine techniques for the eamination of the heart, the brain, the kidneys and endocrine glands in patients with arterial hypertension, discussing the methods with a view to obtainable information, limits of detection, and indications. (orig.) [de

Pulmonary artery-to-pulmonary artery anastomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension

International Nuclear Information System (INIS)

Hodson, J.; Graham, A.; Hughes, J.M.B.; Gibbs, J.S.R.; Jackson, J.E.

2006-01-01

AIM: To describe direct pulmonary artery-to-pulmonary artery anastomoses seen at pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension and discuss their possible significance. MATERIALS AND METHODS: Between 1 August 2000 and 31 July 2004 43 patients (male-to-female ratio 25:18) with a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) underwent selective pulmonary angiography to assess the extent of disease and suitability for surgical pulmonary endarterectomy. The mean pulmonary artery pressure ranged from 27-84 mmHg (average of 51 mmHg). Selective bilateral digital subtraction pulmonary angiograms performed in all individuals were reviewed for the presence of intrapulmonary collaterals. RESULTS: In 15 of the 43 patients (male-to-female ratio =7:8) definite (n=12) or probable (n=3) pulmonary artery-to-pulmonary artery anastomoses were demonstrated. Of the remaining 28 patients in whom intrapulmonary collaterals were not seen it was felt that in 16 the angiograms were of insufficient diagnostic quality (grades 4-5) to exclude their presence. Twelve patients, eight of whom had angiograms of sufficient diagnostic quality (grades 1-3), demonstrated one or more areas of luxury perfusion but intrapulmonary collaterals were not seen. CONCLUSION: Direct pulmonary artery-to-pulmonary artery anastomoses were demonstrated in patients with chronic thromboembolic pulmonary hypertension, which to our knowledge have not been previously described. The importance of these collateral vessels is unclear but they may play a role in the maintenance of pulmonary parenchymal viability in patients with chronic pulmonary embolic disease. The rate of development of these collaterals and their prognostic significance in patients with chronic thromboembolic pulmonary hypertension are areas worthy of further study

Pulmonary artery-to-pulmonary artery anastomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension

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Hodson, J. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Graham, A. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Hughes, J.M.B. [Department of Respiratory Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Gibbs, J.S.R. [Department of Cardiology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Jackson, J.E. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom)]. E-mail: jejackson@hhnt.org

2006-03-15

AIM: To describe direct pulmonary artery-to-pulmonary artery anastomoses seen at pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension and discuss their possible significance. MATERIALS AND METHODS: Between 1 August 2000 and 31 July 2004 43 patients (male-to-female ratio 25:18) with a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) underwent selective pulmonary angiography to assess the extent of disease and suitability for surgical pulmonary endarterectomy. The mean pulmonary artery pressure ranged from 27-84 mmHg (average of 51 mmHg). Selective bilateral digital subtraction pulmonary angiograms performed in all individuals were reviewed for the presence of intrapulmonary collaterals. RESULTS: In 15 of the 43 patients (male-to-female ratio =7:8) definite (n=12) or probable (n=3) pulmonary artery-to-pulmonary artery anastomoses were demonstrated. Of the remaining 28 patients in whom intrapulmonary collaterals were not seen it was felt that in 16 the angiograms were of insufficient diagnostic quality (grades 4-5) to exclude their presence. Twelve patients, eight of whom had angiograms of sufficient diagnostic quality (grades 1-3), demonstrated one or more areas of luxury perfusion but intrapulmonary collaterals were not seen. CONCLUSION: Direct pulmonary artery-to-pulmonary artery anastomoses were demonstrated in patients with chronic thromboembolic pulmonary hypertension, which to our knowledge have not been previously described. The importance of these collateral vessels is unclear but they may play a role in the maintenance of pulmonary parenchymal viability in patients with chronic pulmonary embolic disease. The rate of development of these collaterals and their prognostic significance in patients with chronic thromboembolic pulmonary hypertension are areas worthy of further study.

MDCTA diagnosis of cerebral vessel disease among patients with arterial hypertension

International Nuclear Information System (INIS)

Romanko-Hrushchak, Nataliya

2013-01-01

to study changes involving cerebral vessels in patients with hypertension and various levels of total cardiovascular risk. One hundred and thirty-four patients underwent CT-angiography of intracranial vessels. Ninety-eight of them were diagnosed with hypertension. Taking into consideration high blood pressure, presence of risk factors and target organ damage subjects were divided into 4 groups: with low, medium, high and very high total cardiovascular risk. Control group included 36 patients. They were not diagnosed with hypertension at the time of examination. One hundred and five patients were examined using a 4-slice CT scanner (Toshiba Asteion 4, Toshiba Medical System, Japan), and 29 patients were examined using a 128-slice scanner (Siemens Definition AS+, Siemens Healthcare, Germany) with an injection system. We used iodine-containing contrast agents such as iodixanol and iopromide for angiography. Anatomical and topographic changes of cerebral vessels were most frequently found in hypertensive patients with high and very high total cardiovascular risk. Narrowing of vertebral vessels was the most common change (27 patients (27.55%), 21 patients (21.43%) had narrowing of the right artery, and 6 (6.12%) subjects – of the left one). Tortuous course of internal carotid arteries at the neck level was visualized in 11 patients (11.22%). Narrowing of A1 segment of anterior cerebral artery was noted in 9 patients (9.18%), of the right one – in 8 patients (8.16%), of the left one – in 1 patient (1.02%). Aneurysmal dilation of intracranial vessels was visualized in 6 patients (6.12%). Saccular aneurysm of left internal carotid artery was diagnosed in 2 patients (2.04%), one patient (1.02%) had right internal carotid artery aneurysm and one patient (1.02%) had an aneurysm of the basilar artery. the most common changes of cerebral vessels diagnosed in MDCTA among patients with hypertension included various degrees of narrowing of vertebral vessels, anterior

Tanshinone IIA protects against pulmonary arterial hypertension in broilers.

Science.gov (United States)

Hu, Guoliang; Song, Yalu; Ke, Shanlin; Cao, Huabin; Zhang, Caiying; Deng, Guangfu; Yang, Fei; Zhou, Sihui; Liu, Pei; Guo, Xiaoquan; Liu, Ping

2017-05-01

This investigation was conducted to study the effects of tanshinone IIA (TIIA) on pulmonary arterial hypertension (PAH) in broilers. Two-hundred newly hatched Arbor Acre commercial broilers were randomly divided into 3 groups. All groups, with the exception of the control group (tap water), were given NaCl water (0.3%) starting on the d 15, and broilers in the protected group were fed a diet supplemented with TIIA (2.5 g/kg) starting on the d 15. On d 28, 35, 42, and 49, the ratio of the right ventricular weight to the total ventricular weight (RV: TV) and the values of other biochemical indicators for each group chickens were determined. The concentrations of interleukin-6 (IL-6), interleukin-1β (IL-1β), nuclear factor kappa (NF-κB), and P38 (a mitogen-activated protein kinase) were measured using enzyme-linked immune sorbent assays (ELISA). The results showed that the proportion of chickens in the diseased group with an RV:TV ratio in the range of 0.250 to 0.299 (10%) was significantly higher (25 to 30%) compared to that of the other groups (P chickens was 28%. In addition, the IL-6, IL-1β, NF-κB, and P38 protein concentrations were higher in the diseased group, whereas there were no differences between the control group and the protected group. Moreover, the measurements of body weight, liver function, kidney function and electrolytes showed significant differences between the diseased group and the other groups. These findings suggest that tanshinone IIA may protect broilers from PAH, which is an important piece of information for the poultry industry. © 2016 Poultry Science Association Inc.

[Clinicofunctional features of arterial hypertension in chronic broncho-obstructive syndrome].

Science.gov (United States)

Zadionchenko, V S; Kuz'micheva, N V; Sviridov, A A; Ol'kha, R P; Kashcheeva, E V

2000-01-01

To describe clinicofunctional features of essential and pulmogenic hypertension in chronic bronchoobstructive syndrome, 24-h profile of arterial pressure (AP), intracardiac hemodynamics and to propose differential diagnostic criteria for these hypertension forms. 24-h monitoring of arterial pressure (MAP), cardiohemodynamics, external respiration function (ERF) and blood gases examinations were made in 100 hypertensive subjects with chronic obstructive bronchitis and bronchial asthma. Significant differences were found between the groups of essential and pulmogenic hypertension by major values of MAP, echo-CG and ERF. Early disturbances in diastolic function of both the ventricles in essential and pulmonary hypertension in chronic bronchial obstruction arise long before clinical, x-ray and ECG signs of chronic pulmonary heart. The findings enable formulation of criteria of differential diagnosis of essential and pulmogenic hypertension and identify the latter as an independent nosological entity.

Hemorheological abnormalities in human arterial hypertension

Science.gov (United States)

Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

2014-05-01

Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

Impact of hypertension severity on arterial stiffness, cerebral vasoreactivity, and cognitive performance

Science.gov (United States)

Muela, Henrique Cotchi Simbo; Costa-Hong, Valeria A.; Yassuda, Monica Sanches; Machado, Michel Ferreira; Nogueira, Ricardo de Carvalho; Moraes, Natalia C.; Memória, Claudia Maia; Macedo, Thiago A.; Bor-Seng-Shu, Edson; Massaro, Ayrton Roberto; Nitrini, Ricardo; Bortolotto, Luiz A.

2017-01-01

ABSTRACT. Aging, hypertension (HTN), and other cardiovascular risk factors contribute to structural and functional changes of the arterial wall. Objective: To evaluate whether arterial stiffness (AS) is related to cerebral blood flow changes and its association with cognitive function in patients with hypertension. Methods: 211 patients (69 normotensive and 142 hypertensive) were included. Patients with hypertension were divided into 2 stages: HTN stage-1 and HTN stage-2. The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological (NPE) tests were used to determine cognitive function. Pulse wave velocity was measured using the Complior®. Carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. Middle cerebral artery flow velocity was measured by transcranial Doppler ultrasonography. Results: Both arterial stiffness parameters and cerebral vasoreactivity worsened in line with HTN severity. There was a negative correlation between breath holding index (BHI) and arterial stiffness parameters. Cognitive performance worsened in line with HTN severity, with statistical difference occurring mainly between the HTN-2 and normotension groups on both the MMSE and MoCA. The same tendency was observed on the NPE tests. Conclusion: Hypertension severity was associated with higher AS, worse BHI, and lower cognitive performance. PMID:29354219

Prevalence of arterial hypertension in diabetic patients before and after the JNC-V

DEFF Research Database (Denmark)

Tarnow, L; Rossing, P; Gall, Mari-Anne

1994-01-01

OBJECTIVE: To compare the prevalence of arterial hypertension in patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) according to blood pressure (BP) criteria from the World Health Organization (WHO) and The Fifth Report of the Joint National...... had stage 2 (160-179/100-109 mmHg) hypertension. Two out of three untreated hypertensive patients had isolated systolic hypertension. CONCLUSIONS: The new JNC-V criteria approved by the American Diabetes Association leads to a considerable increase in the prevalence of arterial hypertension...... treatment were classified as hypertensives. RESULTS: In IDDM patients, the prevalence of arterial hypertension rose from 15 to 42% in the normoalbuminuric group, from 26 to 52% in the microalbuminuric group, and from 61 to 79% in the macroalbuminuric group when WHO and JNC-V criteria were compared...

Resistance training controls arterial blood pressure in rats with L-NAME- induced hypertension.

Science.gov (United States)

Araujo, Ayslan Jorge Santos de; Santos, Anne Carolline Veríssimo dos; Souza, Karine dos Santos; Aires, Marlúcia Bastos; Santana-Filho, Valter Joviniano; Fioretto, Emerson Ticona; Mota, Marcelo Mendonça; Santos, Márcio Roberto Viana

2013-04-01

Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (parteries. RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.

Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study

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Berger Ariel

2012-12-01

Full Text Available Abstract Background Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH impacts patterns of healthcare utilization and costs. Methods Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8 who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the “index date,” and claims data were compiled for all study subjects for 6 months prior to their index date (“pretreatment” and 6 months thereafter (“follow-up”; patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. Results A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD age was 52 (10 years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p  Conclusions The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

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

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

2018-04-10

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

[Features of daily rhythm of arterial pressure in patients with primary arterial hypertension and neurogenic syncope conditions].

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Musaeva, Z A; Oknin, V Iu; Khapaev, B A; Fedotova, A V; Veĭn, A M

2002-01-01

A comparative analysis of parameters of systemic BP in patients with primary arterial hypotension (PAH) and in patients with neurogenic syncopes (NS) in the cycle sleep-awake. Blood pressure was investigated in 20 patients with PAH aged 16-44 years and 18 patients with NS aged 16-49 years. 24-h ambulatory monitoring of BP was made on the monitor ABPM-02/M (Meditech, Hungary). Rhythm indices of BP in NS patients corresponded to age normal criteria. 24-h arrhythmia of BP in PAH patients manifests with excessive drop of diastolic BP in sleep (55% patients were overdippers). PAH and NS patients differ maximally by hypotonic load in sleep: 1.0 +/- 0.7% in NS vs 15.4 +/- 3.2% in PAH. Hypotonia episodes in awake PAH patients were registered at each 4th-5th measurement of BP, in NS patients--at each 11th-13th. Heart rate in awake PAH patients is higher than in healthy subjects. Hypotonic load in sleep carries the highest differentially-diagnostic importance. This makes more perspective examinations of such patients in the cycle sleep-awake. The changes observed in PAH patients evidence for activation of cerebral sympathico-adrenal systems participating in baroreflex regulation.

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

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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

Secondary Pulmonary Hypertension and Right-Sided Heart Failure at Presentation in Grave's Disease

OpenAIRE

Ganeshpure, Swapnil Panjabrao; Vaidya, Gaurang Nandkishor; Gattani, Vipul

2012-01-01

A young female presented with evidence of right-sided heart failure and was subsequently found to have significant pulmonary artery hypertension (PAH). Because of her normal left ventricular function and pulmonary capillary wedge pressure, the most probable site of etiology seemed to be the pulmonary vasculature. All the common possible secondary causes of PAH were ruled out, but during the investigations, she was found to have elevated thyroid function tests compatible with the diagnosis of...

[Clinico-statistical analysis of arterial hypertension complicated with hypertensive crisis in Moscow in 2005-2009].

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Gaponova, N I; Plavunov, N F; Tereshchenko, S N; Baratashvili, V L; Abdurakhmanov, V R; Komissarenko, I A; Filippov, D V; Podkopaev, D V

2011-01-01

Clinicostatistical analysis of arterial hypertension complicated with hypertensive crisis using data of Moscow A.S.Puchkov Station of Urgent and Emergent Medical Aid revealed 14% rise in number of hypertensive crises during the period from 2005 to 2009. Number of hypertensive crises increased among persons of young age (18-35 years). Frequency of cerebrovascular complications of hypertensive crises was age dependent with maximal values among men aged 36-74 years and women older than 75 years.

Gender-related difference in arterial elastance during exercise in patients with hypertension.

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Park, Sungha; Ha, Jong-Won; Shim, Chi Young; Choi, Eui-Young; Kim, Jin-Mi; Ahn, Jeong-Ah; Lee, Se-Wha; Rim, Se-Joong; Chung, Namsik

2008-04-01

Exercise intolerance and heart failure with preserved ejection fraction are common in females. Recently, arterial stiffness has been suggested to be a significant contributor in the development of heart failure. How gender difference affects arterial stiffening and its response to exercise is not well known. We hypothesized that arterial elastance index during exercise would be more abnormal in females with hypertension than males. Arterial elastance index was estimated as arterial end systolic pressure/stroke volume controlled for body surface area and was measured at rest and during graded supine bicycle exercise (25 watts, 3-minute increments) in 298 patients with hypertension (149 males; 149 females; mean age, 59). The subjects were divided into 2 groups by gender. Exercise duration was significantly shorter in females compared to males (692+/-222 versus 483+/-128 seconds, Pexercise being significantly higher in females compared to males (0.69+/-0.83 versus 0.43+/-0.69, P=0.018). Arterial elastance index at each stage of exercise up to 75 W was independently associated with decreased exercise duration. In conclusion, despite lower arterial elastance index at rest, the increase during exercise was steeper in women with hypertension, suggesting a gender-related difference in dynamic arterial stiffness. The arterial elastance index during exercise was significantly associated with exercise duration in patients with hypertension.

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol.

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Suen, Colin M; Zhai, Alex; Lalu, Manoj M; Welsh, Christopher; Levac, Brendan M; Fergusson, Dean; McIntyre, Lauralyn; Stewart, Duncan J

2016-05-25

Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies. We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and

Effects of diabetes mellitus and systemic arterial hypertension on elderly patients' hearing.

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Rolim, Laurie Penha; Samelli, Alessandra Giannella; Moreira, Renata Rodrigues; Matas, Carla Gentile; Santos, Itamar de Souza; Bensenor, Isabela Martins; Lotufo, Paulo Andrade

2017-09-21

Chronic diseases can act as an accelerating factor in the auditory system degeneration. Studies on the association between presbycusis and diabetes mellitus and systemic arterial hypertension have shown controversial conclusions. To compare the initial audiometry (A1) with a subsequent audiometry (A2) performed after a 3 to 4-year interval in a population of elderly patients with diabetes mellitus and/or systemic arterial hypertension, to verify whether hearing loss in these groups is more accelerated when compared to controls without these clinical conditions. 100 elderly individuals participated in this study. For the auditory threshold assessment, a previous complete audiological evaluation (A1) and a new audiological evaluation (A2) performed 3-4 years after the first one was utilized. The participants were divided into four groups: 20 individuals in the diabetes mellitus group, 20 individuals in the systemic arterial hypertension group, 20 individuals in the diabetes mellitus/systemic arterial hypertension group and 40 individuals in the control group, matching them with each study group, according to age and gender. ANOVA and Kruskal-Wallis statistical tests were used, with a significance level set at 0.05. When comparing the mean annual increase in the auditory thresholds of the A1 with the A2 assessment, considering each study group and its respective control, it can be observed that there was no statistically significant difference for any of the frequencies for the diabetes mellitus group; for the systemic arterial hypertension group, significant differences were observed after 4kHz. For the diabetes mellitus and systemic arterial hypertension group, significant differences were observed at the frequencies of 500, 2kHz, 3kHz and 8kHz. It was observed that the systemic arterial hypertension group showed the greatest decrease in auditory thresholds in the studied segment when compared to the other groups, suggesting that among the three studied conditions

Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension.

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Weinstein, Ali A; Chin, Lisa M K; Keyser, Randall E; Kennedy, Michelle; Nathan, Steven D; Woolstenhulme, Joshua G; Connors, Gerilynn; Chan, Leighton

2013-05-01

To investigate the effectiveness of an exercise intervention for decreasing fatigue severity and increasing physical activity in individuals with pulmonary arterial hypertension (PAH). A small, phase 2 randomized clinical trial of the effect of aerobic exercise training on fatigue severity and physical activity in patients with idiopathic or PAH associated with other conditions was conducted. Twenty-four patients with PAH (24 female; age: 54.4 ± 10.4 years; BMI: 30.8 ± 7.2 kg/m(2)) participated in the study. A convenience sample was recruited in which 9% (28 of 303) of screened patients were enrolled. The project was carried out in a clinical pulmonary rehabilitation clinic during existing pulmonary rehabilitation program sessions. Patients with PH were randomized into a 10-week program that consisted of patient education only or patient education plus an aerobic exercise-training regimen. Both groups received 20 lectures, two per week over the 10-weeks, on topics related to PAH and its management. The aerobic exercise training consisted of 24-30 sessions of treadmill walking for 30-45 min per session at an intensity of 70-80% of heart rate reserve, three days per week over the 10 weeks. After 10-weeks of intervention, patients receiving aerobic exercise training plus education reported routinely engaging in higher levels of physical activity (p decrease in fatigue severity (p = 0.03). Patients in the education only group did not report changes in fatigue severity or participation in physical activity. The 10-week aerobic exercise training intervention resulted in increased physical activity and decreased fatigue in individuals with PAH. ClinicalTrials.gov Identifier: NCT00678821. Copyright © 2013 Elsevier Ltd. All rights reserved.

Therapeutic strategies in pulmonary hypertension

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Leonello eFuso

2011-04-01

Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

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Ying-Ju Lai

Full Text Available Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH. In addition, Propylthiouracil (PTU, beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2 subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2 subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

Inverse relationship between physical activity and arterial stiffness in adults with hypertension.

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O'Donovan, Cuisle; Lithander, Fiona E; Raftery, Tara; Gormley, John; Mahmud, Azra; Hussey, Juliette

2014-02-01

Physical activity has beneficial effects on arterial stiffness among healthy adults. There is a lack of data on this relationship in adults with hypertension. The majority of studies which have examined physical activity and arterial stiffness have used subjective measures of activity. The aim of this study was to investigate the relationship between objectively measured habitual physical activity and arterial stiffness in individuals with newly diagnosed essential hypertension. Adults attending an outpatient hypertension clinic were recruited into this cross sectional study. Physical activity was measured using a triaxial accelerometer. Pulse wave velocity (PWV) and augmentation index (AIx) were measured using applanation tonometry. Participant's full lipid profile and glucose were determined through the collection of a fasting blood sample. Fifty-three adults [51(14) years, 26 male] participated, 16 of whom had the metabolic syndrome. Inactivity was positively correlated with PWV (r = .53, P arterial stiffness among adults with hypertension.

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

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

2018-06-01

Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

A CASE OF IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION IN MALE

OpenAIRE

Poongavanam Paranthaman; Ramani Bala Subra Manian; Thenrajan Balaji; Jayakrishnan Jayakumar; Govindaraj Ranjani

2016-01-01

Primary Pulmonary Hypertension is a rare disease occurring in 1-2 per million population. It is 2-4 times more common in female. Idiopathic or primary pulmonary hypertension is defined as a disorder with no identifiable cause in which resting mean pulmonary artery pressure in adults is above 25 mmHg and 30 mmHg with exercise. Idiopathic or primary pulmonary hypertension is diagnosed after ruling out all the possible secondary causes of pulmonary hypertension. We are presenting a ...

Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension

International Nuclear Information System (INIS)

Lim, Jisun; Kim, YongHwan; Heo, Jinbeom; Kim, Kang-Hyun; Lee, Seungun; Lee, Sei Won; Kim, Kyunggon; Kim, In-Gyu; Shin, Dong-Myung

2016-01-01

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called “priming” factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK p42/44 and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. - Highlights: • Human BM-derived MSCs primed with C1P have enhanced migratory activity. • C1P primed MSCs increase proliferation, self-renewal, and anti-inflammatory capacity. • C1P priming enhances the therapeutic capacity of MSCs in a PAH animal model.

Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension

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Lim, Jisun [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505 (Korea, Republic of); Kim, YongHwan; Heo, Jinbeom; Kim, Kang-Hyun; Lee, Seungun [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Sei Won [Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Kyunggon [Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, In-Gyu, E-mail: igkim@plaza.snu.ac.kr [Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505 (Korea, Republic of); Shin, Dong-Myung, E-mail: d0shin03@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-04-22

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called “priming” factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK{sup p42/44} and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. - Highlights: • Human BM-derived MSCs primed with C1P have enhanced migratory activity. • C1P primed MSCs increase proliferation, self-renewal, and anti-inflammatory capacity. • C1P priming enhances the therapeutic capacity of MSCs in a PAH animal model.

Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension.

Science.gov (United States)

Walas, Dawid; Nowicki-Osuch, Karol; Alibhai, Dominic; von Linstow Roloff, Eva; Coghill, Jane; Waterfall, Christy; Paton, Julian Fr

2018-01-01

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.

Cerebral lesions in acute arterial hypertension: the characteristic MRI in hypertensive encephalopathy

International Nuclear Information System (INIS)

Schneider, J.P.; Krohmer, S.; Guenther, A.; Zimmer, C.

2006-01-01

Purpose: in the nine years since the posterior reversible (leuc) encephalopathy syndrome (PRES) was first described, a number of causes have been under discussion. These not only include arterial hypertension, i. e. hypertensive crises, but also various toxic substances, i. e. immunosuppressive or chemotherapeutic agents, that are responsible for the formation of the symptoms and characteristic MR tomographic brain findings. Materials and methods: initial and follow-up MRI examinations of 8 patients were analyzed. All patients had acute neurological symptoms (headaches, seizures, visual disorders and vigilance disturbances) together with a detectable hypertensive crisis. Results: MRI disclosed increased signal intensity in subcortical and some cortical lesions in all patient FLAIR sequences. These changes were particularly extensive in the posterior circulation (occipital, cerebellum and brain stem) although they were also detected in brain areas supplied by the carotid artery. However, a cytotoxic genesis of the changes was ruled out in each patient by means of a normal DWI. Furthermore, when the blood pressure was normalized, reversibility of the lesions as proof of the diagnosis was detectable. (orig.)

Secondary arterial hypertension: when, who, and how to screen?

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Rimoldi, Stefano F; Scherrer, Urs; Messerli, Franz H

2014-05-14

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.

A CLINICAL CASE: DIAGNOSTICS OF SHERESHEVSKY TERNER SYNDROME WITH MULTIPLE CONGENITAL ANOMALIES IN MAIN ARTERIES OF A 4 YEAR OLD CHILD, SUFFERING FROM ARTERIAL HYPERTENSION

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A.N. Tsygin

2007-01-01

Full Text Available The article provides a substantiation for the differential diagnostics of the symptomatic arterial hypertension of a 4 year old child, suffering from the arterial hypertension of the presumably renoparenchymal origin. In the course of the clinical examination, the researchers found out coarctation of aorta and hypoplasia of the right renal artery as a part of Shereshevsky-Terner syndrome.Key words: arterial hypertension, Shereshevsky-Terner syndrome, coarctation of aorta, renovascular hypertension.

Relation of epicardial adipose tissue with arterial compliance and stiffness in patients with hypertension.

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Korkmaz, Levent; Cirakoglu, Omer Faruk; Ağaç, Mustafa Tarik; Erkan, Hakan; Korkmaz, Ayca Ata; Acar, Zeydin; Kul, Selim; Hatem, Engin; Çelik, Şükrü

2014-09-01

The main aim of the present study was to investigate the association between epicardial adipose tissue (EAT) and arterial function in patients with asymptomatic hypertension. Patients with hypertension (n = 155) were enrolled consecutively. Patients with decreased arterial compliance (AC) and increased cardioankle vascular index (CAVI) had higher EAT values compared with those with normal AC and CAVI (6.23 ± 1.67 vs 4.91 ± 1.40, P arterial function in patients with asymptomatic hypertension. The link between EAT and arterial stiffness deserves further investigation. © The Author(s) 2013.

[Vascular aging, arterial hypertension and physical activity].

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Schmidt-Trucksäss, A; Weisser, B

2011-11-01

The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. © Georg Thieme Verlag KG Stuttgart · New York.

Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping.

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Morgan, R Garrett; Ives, Stephen J; Walker, Ashley E; Cawthon, Richard M; Andtbacka, Robert H I; Noyes, Dirk; Lesniewski, Lisa A; Richardson, Russell S; Donato, Anthony J

2014-06-01

Telomere shortening in arteries could lead to telomere uncapping and cellular senescence, which in turn could promote the development of hypertension. To assess the novel role of arterial telomere dysfunction in hypertension, we compared mean telomere length (qPCR), telomere uncapping (serine 139 phosphorylated histone γ-H2A.X (γ-H2) localized to telomeres: ChIP), and tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence (P53 bound to P21 gene promoter: ChIP) in arteries from 55 age-matched hypertensive and nonhypertensive individuals. Arterial mean telomere length was not different in hypertensive patients compared with nonhypertensive individuals (P = 0.29). Arterial telomere uncapping and P53/P21-induced senescence were two-fold greater in hypertensive patients compared with nonhypertensive individuals (P = 0.04 and P = 0.02, respectively). Arterial mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence (r = -0.02, P = 0.44 and r = 0.01, P = 0.50, respectively), but telomere uncapping was a highly influential covariate for the hypertension group difference in P53/P21-induced senescence (r = 0.62, P hypertension status (P = 0.03), whereas mean telomere length was not (P = 0.68). Collectively, these findings demonstrate that arterial telomere uncapping and P53/P21-induced senescence are linked to hypertension independently of mean telomere length, and telomere uncapping influences hypertension status more than mean telomere length.

Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension.

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Brandie D Wagner

Full Text Available Although many predictors have been evaluated, a set of strong independent prognostic mortality indicators has not been established in children with pediatric pulmonary arterial hypertension (PAH. The aim of this study was to identify a combination of clinical and molecular predictors of survival in PAH.This single-center, retrospective cohort study was performed from children with PAH between 2001 and 2008 at Children's Hospital Colorado. Blood samples from 83 patients (median age of 8.3 years-old were obtained. We retrospectively analyzed 46 variables, which included 27 circulating proteins, 7 demographic variables and 12 hemodynamic and echocardiographic variables for establishing the best predictors of mortality. A data mining approach was utilized to evaluate predictor variables and to uncover complex data structures while performing variable selection in high dimensional problems.Thirteen children (16% died during follow-up (median; 3.1 years and survival rates from time of sample collection at 1 year, 3 years and 5 years were 95%, 85% and 79%, respectively. A subset of potentially informative predictors were identified, the top four are listed here in order of importance: Tissue inhibitors of metalloproteinases-1 (TIMP-1, apolipoprotein-AI, RV/LV diastolic dimension ratio and age at diagnosis. In univariate analysis, TIMP-1 and apolipoprotein-AI had significant association with survival time (hazard ratio [95% confidence interval]: 1.25 [1.03, 1.51] and 0.70 [0.54-0.90], respectively. Patients grouped by TIMP-1 and apolipoprotein-AI values had significantly different survival risks (p<0.01.Important predictors of mortality were identified from a large number of circulating proteins and clinical markers in this cohort. If confirmed in other populations, measurement of a subset of these predictors could aid in management of pediatric PAH by identifying patients at risk for death. These findings also further support a role for the clinical

Screening of Chronic Obstructive Pulmonary Disease Patients for Pulmonary Arterial Hypertension Using Two-Dimensional Transthoracic Doppler Echocardiography in Tertiary Care Hospital in India

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Vinay Mahishale

2015-01-01

Full Text Available Background: Chronic obstructive pulmonary disease (COPD and pulmonary arterial hypertension (PAH are common and underdiagnosed medical conditions in India. Prevalence of these chronic diseases is high both in rural and urban areas. However, the exact prevalence of PAH in Indian COPD patients is unclear. Comorbid conditions like PAH have a great impact on the outcome of COPD in the form of severity, exacerbations, morbidity, and mortality. Right heart catheterization remains the gold standard test for diagnosis of PAH, but it is invasive and practically not feasible. Aims and objectives: The present study objective was to screen COPD patients for PAH using two-dimensional transthoracic Doppler echocardiography (ECHO in Tertiary Care Hospital. Results: A total of 2040 patients with a confirmed diagnosis of COPD were enrolled in the study. Among these patients, 1509 were males (73.9%, 531 were females (23.06%, and 1428 were known or ex-smokers (70%. None of the females were smokers, but there was a history of biomass fuel exposure for >10 years. As per global initiative for chronic obstructive lung disease criteria, mild, moderate, severe, and very severe COPD was noted in 525,629,511, and 375 patients, respectively. When they were screened using ECHO, prevalence of PAH was 41.96% as 856 subjects had PAH. Prevalence of PAH among mild, moderate, severe, and very severe COPD was 23.8%, 34.81%, 48.53%, and 70.4%, respectively. There was a linear relationship between PAH and severity of COPD. Conclusion: PAH is very common in COPD patients in India. As the severity of COPD increased, the frequency and degree of PAH also increased. ECHO is an excellent tool for detection of PAH in COPD patients. All patients with severe to very severe COPD should be routinely screened by ECHO for PAH and with mild to moderate COPD, who have dyspnea out of proportion to their clinical condition should also be screened for PAH.

[Ultrasonographic study of blood flow in the renal arteries of patients with arterial hypertension].

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Makarenko, E S; Dombrovskiĭ, V I; Nelasov, N Iu

2012-01-01

Vascular duplex ultrasound duplex with simultaneous ECG registration was made to estimate the quantitative and time parameters of blood flow in the renal arteries with grade 1-2 arterial hypertension. There were increases in vascular resistance indices and acceleration phase index and a reduction in systolic phase index. There were correlations of the time parameters of blood flow in the renal arteries with age and lipidogram values.

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

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Hardin EA

2016-11-01

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

Venous digital subtraction angiography of the renal arteries in hypertensive patients

International Nuclear Information System (INIS)

Brecht, G.; Harder, T.; Franken, T.

1984-01-01

We carried out 1890 venous digital subtraction angiograms; this included 113 patients with hypertension in order to exclude renal artery stenosis. On four occasions it was used following surgery on a renal artery. Renal artery stenosis or occlusion was demonstrated in twelve patients, and other vascular diseases or anomalies were found in 24. Two abnormal renal arteries were found following renal artery surgery. The results are compared with smaller groups of patients examined by DSA, and with the results of conventional subtraction methods reported in the literature. In only eight patients (6.8%) DSA provided insufficient information and had to be supplemented by aortography. The method has proved to be a valuable and simple screening method for the investigation of hypertension. (orig.) [de

Precision medicine and personalising therapy in pulmonary hypertension: seeing the light from the dawn of a new era.

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Savale, Laurent; Guignabert, Christophe; Weatherald, Jason; Humbert, Marc

2018-06-30

Pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) include different cardiopulmonary disorders in which the interaction of multiple genes with environmental and behavioural factors modulates the onset and the progression of these severe conditions. Although the development of therapeutic agents that modulate abnormalities in three major pathobiological pathways for PAH has revolutionised our approach to the treatment of PAH, the long-term survival rate remains unsatisfactory. Accumulating evidence has underlined that clinical outcomes and responses to therapy in PAH are modified by multiple factors, including genetic variations, which will be different for each individual. Since precision medicine, also known as stratified medicine or personalised medicine, aims to better target intervention to the individual while maximising benefit and minimising harm, it has significant potential advantages. This article aims to assemble and discuss the different initiatives that are currently underway in the PH/PAH fields together with the opportunities and prospects for their use in the near future. Copyright ©ERS 2018.

Severe hypertension due to renal polar artery stenosis in an adolescent treated with coil embolization

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Docx, Martine K. [Koningin Paola Kinderziekenhuis, Department of Paediatrics, Chronic Diseases and Hypertension, Antwerp (Belgium); Vandenberghe, Philippe [Koningin Paola Kinderziekenhuis, Department of Paediatric Cardiology, Antwerp (Belgium); Maleux, Geert [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Gewillig, Marc [University Hospitals Leuven, Department of Paediatric Cardiology, Leuven (Belgium); Mertens, Luc [Hospital for Sick Children, Paediatric Cardiology, Toronto (Canada)

2009-11-15

A 12-year-old boy presented with severe arterial hypertension due to a severe subsegmental renal artery stenosis. Treatment consisted of selective embolization of the stenosed polar artery, which resulted in near normalization of the arterial pressures. Renal artery stenosis should always be considered, even in young adolescents, as a cause for arterial hypertension. Only selective angiography was able to demonstrate the subsegmental artery stenosis in this patient. (orig.)

Severe hypertension due to renal polar artery stenosis in an adolescent treated with coil embolization

International Nuclear Information System (INIS)

Docx, Martine K.; Vandenberghe, Philippe; Maleux, Geert; Gewillig, Marc; Mertens, Luc

2009-01-01

A 12-year-old boy presented with severe arterial hypertension due to a severe subsegmental renal artery stenosis. Treatment consisted of selective embolization of the stenosed polar artery, which resulted in near normalization of the arterial pressures. Renal artery stenosis should always be considered, even in young adolescents, as a cause for arterial hypertension. Only selective angiography was able to demonstrate the subsegmental artery stenosis in this patient. (orig.)

Fibrinogen plasma concentration is an independent marker of haemodynamic impairment in chronic thromboembolic pulmonary hypertension

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Hennigs, Jan K.; Baumann, Hans Jörg; Lüneburg, Nicole; Quast, Gesine; Harbaum, Lars; Heyckendorf, Jan; Sydow, Karsten; Schulte-Hubbert, Bernhard; Halank, Michael; Klose, Hans

2014-01-01

Fibrinogen has a crucial role in both inflammation and coagulation, two processes pivotal for the pathogenesis of pulmonary hypertension. We therefore aimed to investigate whether fibrinogen plasma concentrations a) are elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and b) may serve as a novel biomarker for haemodynamic impairment. In a dual-centre, retrospective analysis including 112 patients with PAH (n = 52), CTEPH (n = 49) and a control cohort of patients with suspected PAH ruled out by right heart catheterisation (n = 11), we found fibrinogen plasma concentrations to be increased in patients with PAH (4.1 ± 1.4 g/l) and CTEPH (4.3 ± 1.2 g/l) compared to control patients (3.4 ± 0.5 g/l, p = 0.0035 and p = 0.0004, respectively). In CTEPH patients but not in PAH patients fibrinogen was associated with haemodynamics (p < 0.036) and functional parameters (p < 0.041). Furthermore, fibrinogen was linked to disease severity (WHO functional class, p = 0.017) and independently predicted haemodynamic impairment specifically in CTEPH (p < 0.016). Therefore, fibrinogen seems to represent an important factor in CTEPH pathophysiology and may have the potential to guide clinical diagnosis and therapy. PMID:24770447

Radioimmunological thromboxane concentrations in arterial blood of cigarette smokers and hypertensive subjects

International Nuclear Information System (INIS)

Krause, F.J.

1987-01-01

Thromboxane concentrations were investigated in the arterial plasma of 79 patients (24 smokers, 23 nonsmokers, 16 hypertensives, 16 normotensives) with periphered obstructive arterial disease. The thromboxane investigation was made by radioimmunoassay, whose realization was modified. The results indicate that nonsmokers have significantly lower thromboxane levels than smokers, whereas there is no statistically significant difference between hypertensives and normotensives. The findings coincide with the increased risk for arteriosclerosis of smokers, that doesn't work for hypertensives. (orig.) [de

Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation.

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Ribichini, Flavio; Pighi, Michele; Zivelonghi, Carlo; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

2013-01-01

Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The presence of a renal artery stenosis may be both a cause of secondary hypertension and a contraindication to RSD if a renal artery stent is implanted; therefore, the definition of the functional importance of a renal artery stenosis in a patient with refractory hypertension is crucial. We describe the imaging and functional intravascular assessment of an angiographically severe stenosis of the renal artery in a patient with severe refractory hypertension, by means of intravascular ultrasound (IVUS), and measurement of the translesional pressure gradient with a pressure wire. Pressure wire examination excluded any severity of the stenosis, and IVUS showed the presence of a dissected plaque that resolved spontaneously after 3 months of intensive medical therapy and high-dose statin. Subsequently the patient was treated with RSD, achieving a significant effect on blood pressure control. Intravascular imaging and functional assessment of renal artery anatomy in patients with atherosclerotic disease may prove particularly suited to patients with refractory hypertension and multilevel vascular disease who are considered for endovascular therapies, either renal artery stenting or RSD.

Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations

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Tiede Henning

2011-07-01

Full Text Available Abstract Background Mutations in the bone morphogenetic protein receptor 2 (BMPR2 gene can lead to idiopathic pulmonary arterial hypertension (IPAH. This study prospectively screened for BMPR2 mutations in a large cohort of PAH-patients and compared clinical features between BMPR2 mutation carriers and non-carriers. Methods Patients have been assessed by right heart catheterization and genetic testing. In all patients a detailed family history and pedigree analysis have been obtained. We compared age at diagnosis and hemodynamic parameters between carriers and non-carriers of BMPR2 mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the BMPR2 promoter region, the ACVRL1, Endoglin, and SMAD8 genes have been analysed. Results Of the 231 index patients 22 revealed a confirmed familial aggregation of the disease (HPAH, 209 patients had sporadic IPAH. In 49 patients (86.3% of patients with familial aggregation and 14.3% of sporadic IPAH mutations of the BMPR2 gene have been identified. Twelve BMPR2 mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than non-carriers (38.53 ± 12.38 vs. 45.78 ± 11.32 years, p Conclusion This study identified in a large prospectively assessed cohort of PAH- patients new BMPR2 mutations, which have not been described before and confirmed previous findings that mutation carriers are younger at diagnosis with a more severe hemodynamic compromise. Thus, screening for BMPR2 mutations may be clinically useful.

Upfront triple combination therapy-induced pulmonary edema in a case of pulmonary arterial hypertension associated with Sjogren's syndrome

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Kimikazu Takeuchi

Full Text Available Clinical efficacy of combination therapy using vasodilators for pulmonary arterial hypertension (PAH is well established. However, information on its safety are limited. We experienced a case of primary Sjogren's syndrome associated with PAH where the patient developed pulmonary edema immediately after the introduction of upfront triple combination therapy. Although the combination therapy successfully stabilized her pre-shock state, multiple ground glass opacities (GGO emerged. We aborted the dose escalation of epoprostenol and initiated continuous furosemide infusion and noninvasive positive pressure ventilation (NPPV, but this did not prevent an exacerbation of pulmonary edema. Chest computed tomography showing diffuse alveolar infiltrates without inter-lobular septal thickening suggests the pulmonary edema was unlikely due to cardiogenic pulmonary edema and pulmonary venous occlusive disease. Acute respiratory distress syndrome was also denied from no remarkable inflammatory sign and negative results of drug-induced lymphocyte stimulation tests (DLST. We diagnosed the etiological mechanism as pulmonary vasodilator-induced trans-capillary fluid leakage. Following steroid pulse therapy dramatically improved GGO. We realized that overmuch dose escalation of epoprostenol on the top of dual upfront combination poses the risk of pulmonary edema. Steroid pulse therapy might be effective in cases of vasodilator-induced pulmonary edema in Sjogren's syndrome associated with PAH. Keywords: Steroid therapy, Ground glass opacity, Inter-lobular septal thickening, Epoprostenol, Acute respiratory distress syndrome, Trans-capillary fluid leakage

Macitentan for the treatment of pulmonary arterial hypertension

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Kholdani CA

2014-11-01

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

Renal Artery Stenosis in Patients with Resistant Hypertension: Stent It or Not?

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Van der Niepen, Patricia; Rossignol, Patrick; Lengelé, Jean-Philippe; Berra, Elena; Sarafidis, Pantelis; Persu, Alexandre

2017-01-01

After three large neutral trials in which renal artery revascularization failed to reduce cardiovascular and renal morbidity and mortality, renal artery stenting became a therapeutic taboo. However, this is probably unjustified as these trials have important limitations and excluded patients most likely to benefit from revascularization. In particular, patients with severe hypertension were often excluded and resistant hypertension was either poorly described or not conform to the current definition. Effective pharmacological combination treatment can control blood pressure in most patients with renovascular hypertension. However, it may also induce further renal hypoperfusion and thus accelerate progressive loss of renal tissue. Furthermore, case reports of patients with resistant hypertension showing substantial blood pressure improvement after successful revascularization are published over again. To identify those patients who would definitely respond to renal artery stenting, properly designed randomized clinical trials are definitely needed.

Low Complication Rates With Totally Implantable Access Port Use in Epoprostenol Treatment of Pulmonary Hypertension

NARCIS (Netherlands)

Dickinson, Michael G.; Scholvinck, Elisabeth H.; Boonstra, Anco; Vonk-Noordegraaf, Anton; Snijder, Repke J.; Berger, Rolf M. F.

Background: Among patients with advanced pulmonary arterial hypertension (PAH) who are receiving epoprostenol treatment, complications due to the delivery system are known to be a cause of serious morbidity and mortality. In this study, we aimed to outline the complications associated with the use

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

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Shilpa Shah

2017-10-01

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

Urinoma and arterial hypertension complicating neonatal renal candidiasis

International Nuclear Information System (INIS)

Sirinelli, D.; Schmit, P.; Biriotti, V.; Bensman, A.; Lupold, M.

1987-01-01

During antibiotic treatment for E.coli urinary tract infection and meningitis, a male new born developed a Candida albicans urinary tract infection with a mycotic kidney abcess and pelvicalyceal fungus balls diagnosed by US investigations and confirmed by radiology. Three weeks later a perirenal urinoma with arterial hypertension developed. After surgical treatment of the urinoma the arterial pressure returned to normal. (orig.)

Urinoma and arterial hypertension complicating neonatal renal candidiasis

Energy Technology Data Exchange (ETDEWEB)

Sirinelli, D; Schmit, P; Biriotti, V; Bensman, A; Lupold, M

1987-02-01

During antibiotic treatment for E.coli urinary tract infection and meningitis, a male new born developed a Candida albicans urinary tract infection with a mycotic kidney abcess and pelvicalyceal fungus balls diagnosed by US investigations and confirmed by radiology. Three weeks later a perirenal urinoma with arterial hypertension developed. After surgical treatment of the urinoma the arterial pressure returned to normal.

Pharmacoeconomic analysis of ischemic stroke therapy in patients with arterial hypertension

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Mashin V.V.

2010-09-01

Full Text Available Pharmacoeconomic parameters have been examined in patients with ischemic stroke who have suffered from arterial hypertension, depending on use of antihypertensive therapy. The role of antihypertensive therapy as a factor that significantly reduces the treatment costs and improves stroke outcome has been proved. The research results show the importance of integrated analysis of clinical and economical factors in the treatment of patients with arterial hypertension

The evaluation of arterial stiffness of essential hypertension and white coat hypertension in children: a case-control study.

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Tokgöz, Semiha Terlemez; Yılmaz, Dilek; Tokgöz, Yavuz; Çelik, Bülent; Bulut, Yasin

2018-03-01

The aim of this study was to determine and compare cardiovascular risks by assessing arterial stiffness in children with essential hypertension and white coat hypertension. Paediatric patients followed up with essential hypertension and white coat hypertension diagnoses and with no established end organ damage were involved in the study. Arterial stiffness in children included in the study was evaluated and compared by using the oscillometric device (Mobil-O-Graph) method. A total of 62 essential hypertension (34 male, 28 female), 38 white coat hypertension (21 male, 17 female), and 60 healthy controls (33 male, 27 female) were assessed in the present study. Pulse wave velocity of the essential hypertension, white coat hypertension, and control group was, respectively, as follows: 5.3±0.6 (m/s), 5.1±0.4 (m/s), 4.3±0.4 (m/s) (pcoat hypertension were found to be higher compared with the control group. This level was identified as correlated with the duration of hypertension in both patient groups (pcoat hypertension was impaired compared with healthy children. This finding has made us think that white coat hypertension is not an innocent clinical situation. This information should be taken into consideration in the follow-up and treatment approaches of the patients.

[Effect of disease severity on upper extremity muscle strength, exercise capacity, and activities of daily living in individuals with pulmonary arterial hypertension].

Science.gov (United States)

Özcan Kahraman, Buse; Özsoy, İsmail; Acar, Serap; Özpelit, Ebru; Akdeniz, Bahri; Sevinç, Can; Savcı, Sema

2017-07-01

Pulmonary arterial hypertension (PAH) is a rare disease. Although muscle strength, exercise capacity, quality of life, and activities of daily living of patients with PAH are affected, it is not known how they are affected by disease severity. The purpose of the present study was to investigate effects of disease severity on upper extremity muscle strength, exercise capacity, and performance of activities of daily living in patients with PAH. Twenty-five patients with disease severity classified according to the New York Heart Association (NYHA) as functional class II (n=14) or class III (n=11) were included in the study. Upper-extremity exercise capacity and limitations in performing activities of daily living were assessed with 6-minute pegboard and ring test (6PBRT) and the Milliken activities of daily living scale (MAS), respectively. Shoulder flexion, elbow extension, elbow flexion muscle strength, and handgrip strength were measured with dynamometer. There were no significant differences in age, gender, body mass index, or mean pulmonary artery pressure between groups (p>0.05). The 6PBRT, MAS, and elbow flexion (right) and grip strength (right and left) results were significantly lower in NYHA III group than in NYHA II group (p=0.004, p=0.002, p=0.043, p=0.002 and p=0.003, respectively). There was no significant difference in shoulder flexion, elbow flexion (left), or elbow extension between groups (p>0.05). Results suggest that upper extremity exercise capacity, elbow flexion muscle strength (right), and handgrip strength decrease and that limitations in activities of daily living grow as disease severity increases in patients with PAH. When planning rehabilitation programs, disease severity should be considered and evaluations and treatments for the upper extremities should be included.

Denervation (ablation) of nerve terminalis in renal arteries: early results of interventional treatment of arterial hypertension in Poland.

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Bartuś, Krzysztof; Sadowski, Jerzy; Kapelak, Bogusław; Zajdel, Wojciech; Godlewski, Jacek; Bartuś, Stanisław; Bochenek, Maciej; Bartuś, Magdalena; Żmudka, Krzysztof; Sobotka, Paul A

2013-01-01

Arterial hypertension is one of the main causes of cardiovascular disease morbidity and overall mortality. To report the single centre experiences with changes in arterial blood pressure (BP) in patients after intra-arterial application of radiofrequency (RF) energy to cause renal sympathetic efferent and somatic afferent nerve and report vascular and kidney safety in a six month follow up. Twenty-eight patients, with hypertension despite medical therapy (median age 52.02 years, range 42-72 years) consented to therapeutic renal nerve ablation. SIMPLICITY RF catheters and generator provided by Ardian (currently Medtronic Inc., USA) were used to perform renal artery angiography and ablation. The mean BP at baseline, and after one month, three months and six months were measured [mm Hg]: systolic 176.6; 162.3 (p = 0.004); 150.6 (p arterial renal nerve denervation was not associated with either vascular or renal complications out to six months. Nerve ablation of renal arteries led to significant reduction of mean values of arterial systolic, diastolic BP and significant reduction of pulse pressure. The Polish experience is not significantly different compared to that reported in the Symplicity I and Symplicity II international cohorts. The long term durability of this therapy and its application to earlier stages of hypertension or other disease states will require further investigation.

INSTRUMENTAL AND DIAGNOSTIC CRITERIA OF HEMODYNAMIC DISORDERS AND ENDOTHELIAL DYSFUNCTION CORRECTION IN PREGNANTS WITH ARTERIAL HYPERTENSION

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S. M. Heryak

2014-12-01

Conclusions. It was found that the brachial artery ultrasound measuring and occlusive plethysmography procedure by Dietz is an early and safe method of endothelial dysfunction diagnostic in pregnants with hypertension. Doppler ultrasound of blood flow in uterine, umbilical arteries, and middle cerebral arteries of the fetus allows timely diagnosis of the side effect of antihypertensive drugs on the fetus. The therapy of choice for pregnants with Stage II Arterial Hypertension should be based on methyldopa and calcium channel antagonists or selective beta-blockers combination. Highly selective beta-blockers with vasodilative effect (nebivolol hydrochloride and L-arginine (Tivortin allow to prevent perinatal adverse effects of antihypertensive therapy, to correct hemodynamic disorders and endothelial dysfunction in pregnants with arterial hypertension. KEY WORDS: arterial hypertension, uterine-placental hemodynamics, endothelial dysfunction

Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.

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Hasler, Elisabeth D; Müller-Mottet, Séverine; Furian, Michael; Saxer, Stéphanie; Huber, Lars C; Maggiorini, Marco; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

2016-07-01

Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Small artery structure is an independent predictor of cardiovascular events in essential hypertension

DEFF Research Database (Denmark)

Mathiassen, Ole Norling; Buus, Niels Henril; Sihm, Inger

2007-01-01

Objective Structural abnormality of resistance arteries is a characteristic pathophysiological phenomenon in essential hypertension and can be assessed in vitro as an increase in the media : lumen ratio (M : L) of isolated small arteries. We have investigated whether M: L is a risk predictor......). Conclusion Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk. J Hypertens 25:1021-1026 Q 2007 Lippincott Williams & Wilkins. Journal of Hypertension 2007, 25:1021-1026...... in uncomplicated essential hypertensive patients. Recently, high M: L was demonstrated as a prognostic marker in patients at high cardiovascular risk, including normotensive type 2 diabetic patients. Since diabetes is associated with pressure-independent changes in M: L, the relevance of this finding to essential...

Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.

Science.gov (United States)

Li, Fangwei; Shi, Wenhua; Wan, Yixin; Wang, Qingting; Feng, Wei; Yan, Xin; Wang, Jian; Chai, Limin; Zhang, Qianqian; Li, Manxiang

2017-12-01

The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro .