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Sample records for arterial hypertension pah

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

    Science.gov (United States)

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  2. Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH).

    Science.gov (United States)

    Rashid, Jahidur; Patel, Brijeshkumar; Nozik-Grayck, Eva; McMurtry, Ivan F; Stenmark, Kurt R; Ahsan, Fakhrul

    2017-03-28

    The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH. Thus, we prepared porous PLGA particles of sildenafil using a water-in-oil-in-water double emulsion solvent evaporation method with polyethyleneimine (PEI) as a porosigen and characterized the formulations for surface morphology, respirability, in-vitro drug release, and evaluated for in vivo absorption, alveolar macrophage uptake, and safety. PEI increased the particle porosity, drug entrapment, and produced drug release for 36h. Fluorescent particles showed reduced uptake by alveolar macrophages. The polymeric particles were safe to rat pulmonary arterial smooth muscle cell and to the lungs, as evidenced by the cytotoxicity assay and analyses of the injury markers in the bronchoalveolar lavage fluid, respectively. Intratracheally administered sildenafil particles elicited more pulmonary specific and sustained vasodilation in SUGEN-5416/hypoxia-induced PAH rats than oral, intravenous, or intratracheal plain sildenafil did, when administered at the same dose. Overall, true to the hypothesis, this study shows that inhaled PLGA particles of sildenafil can be administered, as a substitute for oral form of sildenafil, at a reduced dose and longer dosing interval.

  3. Management of pulmonary arterial hypertension.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2013-02-01

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

  4. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

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

  5. Management of Pulmonary Arterial Hypertension in Children

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Treatment options for paediatric pulmonary arterial hypertension

    NARCIS (Netherlands)

    Berger, R M F; Bonnet, D

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a serious, progressive condition, which can present idiopathically or secondary to conditions such as systemic sclerosis or congenital heart disease. The condition exists in both adult and paediatric forms, which possess several similar characteristics. Adult

  8. The Relationship between Serum Pro‐Brain Natriuretic Peptide (Pro‐BNP Levels and Pulmonary Arterial Hypertension (PAH in Patients with Limited Scleroderma

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    Seyedeh Zahra Mirfeizi

    2014-08-01

    Full Text Available Introduction: Pulmonary arterial hypertension (PAH is a late progressive sclerodermarelated complication, which can lead to right heart failure and cor pulmonale. Given that cardiac catheterization is a diagnostic method of choice for PAH, and considering the high risks of this method, the purpose of this study was to evaluate the relationship between serum Pro‐Brain natriuretic peptide (Pro‐BNP Levels and PAH in patients with limited scleroderma. Materials and Methods: In this cross sectional study , during June 2011‐ Dec 2013, referring patients to two major educational hospitals, Mashhad‐ Iran, with scleroderma, who were afflicted with the disease for at least two years (or more, were enrolled in the study if they met the inclusion and exclusion criteria. All the patients underwent echocardiography to determine the pulmonary artery pressure (PAP. Afterwards, the subjects were referred to a lung center for performing body plethysmography, carbon monoxide diffusing capacity (DLCO, and 6‐ minute walk test (6MWT. Pro‐BNP Serum level was determined using flourescent immune assay method. Results: The present study included 20 patients (18 female subjects with the mean age of 43.28±9.56 yrs, and the mean pro‐BNP level of 138 pg/ml. The logarithmic correlation between PAP values, Forced Vital Capacity /DLCO ratio, and pro‐BNP level, which was measured using Pearson's correlation coefficient, showed a significant association among these variables( respectively, r=0.76, P0.001; r=0.677, P=0.011. Moreover, the DLCO decrease was associated with increasing pro‐BNP level, though this relationship was not significant. Conclusion: This study showed that there was a significant relationship between the serum levels of pro‐BNP marker and increased PAP in the echocardiography, DLCO reduction, and FVC/DLCO increase. In fact, this serum marker can be used in patients with systemic scleroderma (SSc to evaluate the status of PAH.

  9. Pulmonary Arterial Hypertension

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  11. Potassium channels in pulmonary arterial hypertension.

    Science.gov (United States)

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.

  12. Sildenafil in pediatric pulmonary arterial hypertension.

    Science.gov (United States)

    Dhariwal, A K; Bavdekar, S B

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. Management of pulmonary arterial hypertension.

    Science.gov (United States)

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

    2015-05-12

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

  15. Role of oxidized lipids in pulmonary arterial hypertension

    OpenAIRE

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

    2016-01-01

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

  16. Arterial hypertension and cancer.

    Science.gov (United States)

    Milan, Alberto; Puglisi, Elisabetta; Ferrari, Laura; Bruno, Giulia; Losano, Isabel; Veglio, Franco

    2014-05-15

    Arterial hypertension and cancer are two of the most important causes of mortality in the world; correlations between these two clinical entities are complex and various. Cancer therapy using old (e.g., mitotic spindle poisons) as well as new (e.g., monoclonal antibody) drugs may cause arterial hypertension through different mechanisms; sometimes the increase of blood pressure levels may be responsible for chemotherapy withdrawal. Among newer cancer therapies, drugs interacting with the VEGF (vascular endothelial growth factors) pathways are the most frequently involved in hypertension development. However, many retrospective studies have suggested a relationship between antihypertensive treatment and risk of cancer, raising vast public concern. The purposes of this brief review have then been to analyse the role of chemotherapy in the pathogenesis of hypertension, to summarize the general rules of arterial hypertension management in this field and finally to evaluate the effects of antihypertensive therapy on cancer disease.

  17. Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

    Science.gov (United States)

    Charalampopoulos, Athanasios; Howard, Luke S; Tzoulaki, Ioanna; Gin-Sing, Wendy; Grapsa, Julia; Wilkins, Martin R; Davies, Rachel J; Nihoyannopoulos, Petros; Connolly, Susan B; Gibbs, J Simon R

    2014-12-01

    The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH.

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

    Directory of Open Access Journals (Sweden)

    M. Humbert

    2010-03-01

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

  19. Fatal dissection of the pulmonary artery in pulmonary arterial hypertension

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    B. Degano

    2009-09-01

    Full Text Available A 41-yr-old patient with chronic stable idiopathic pulmonary arterial hypertension (PAH presented with sudden chest pain and unusual dyspnoea during physical exertion. The patient had been diagnosed with PAH at the age of 12 yrs and was in New York Heart Association functional class I/II. The patient was being treated with an anticoagulant regimen, low-dose diuretics and continuous intravenous epoprostenol therapy. A computed tomography scan showed ancient massive thrombi in dilated central pulmonary arteries, which were not haemodynamically significant (perfusion lung scans did not demonstrate segmental or larger defects, and extensive dissection of the right pulmonary artery starting from the intermediate branch. Due to the extensiveness of the dissection, the patient was immediately considered for heart–lung transplantation, but died 72 h after the onset of symptoms. Permission for post mortem examination was denied. Pulmonary artery dissection should be suspected in PAH patients presenting with chest pain and worsening dyspnoea. In the current case, the factors possibly associated with increased risk for dissection may include dilatation of the pulmonary artery, local inflammation favoured by in situ thrombosis, and acute increase of pulmonary pressure secondary to physical exertion. Extensive pulmonary artery dissection is a life-threatening complication of PAH, and urgent heart/lung transplantation might be the treatment of choice in eligible patients. In addition, better identification of the risk factors for pulmonary artery dissection may help in considering transplantation for selected patients at risk.

  20. Pulmonary arterial hypertension in pregnancy.

    Science.gov (United States)

    Običan, Sarah G; Cleary, Kirsten L

    2014-08-01

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

  1. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  2. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    OpenAIRE

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in ele...

  3. Pulmonary arterial hypertension: a current review of pharmacological management.

    Science.gov (United States)

    Sahni, Sonu; Ojrzanowski, Marcin; Majewski, Sebastian; Talwar, Arunabh

    2016-01-01

    Pulmonary hypertension (PHTN) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventricular failure and death. At present there is no cure for pulmonary arterial hypertension (PAH); however over the past decade targeted pharmaceutical options have become available for the treatment of PAH. Prior to evaluation for therapeutic options a definitive diagnosis of pulmonary arterial hypertension must be made via comprehensive physical exam and definitive diagnostic testing. Screening test of choice remains echocardiography and gold standard for definitive diagnosis is right heart catheterization. Once the establishment of a diagnosis of PAH is made therapeutic options may be a possibility based on a diagnostic algorithm and disease severity of the PAH patient. There are different classes of medications available with different mechanisms of actions which net a vasodilatory effect and improve exercise tolerance, quality of life as well and survival.

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

    NARCIS (Netherlands)

    Zijlstra, Willemijn

    2017-01-01

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

  5. The Warburg effect: A new story in pulmonary arterial hypertension.

    Science.gov (United States)

    Peng, Hongyan; Xiao, Yunbin; Deng, Xicheng; Luo, Jingfei; Hong, Chenliang; Qin, Xuping

    2016-10-01

    Pulmonary arterial hypertension (PAH) is a rare yet fatal condition that is characterized by a continuous and notable elevation of pulmonary arterial pressure (PAP), resulting in right heart failure and death. Pulmonary arterial remodelling does not result from abnormal proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) but from pulmonary arterial endothelial cell (PAEC) dysfunction. However, the pathological mechanism of these two types of vascular cells in pulmonary artery remodelling is unclear. The Warburg effect describes aerobic glycolysis wherein cells commonly reprogram their energy metabolism to preferentially utilize glycolysis over oxidative phosphorylation for ATP production. Recent research has demonstrated that the Warburg effect plays a significant role in the development of PAH, which involves the abnormal proliferation of PASMCs and endothelial dysfunction. This review attempts to illustrate the functions of the Warburg effect in PAH, which may provide a new therapeutic target for PAH treatment.

  6. Treatment options for paediatric pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    R.M.F. Berger

    2010-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a serious, progressive condition, which can present idiopathically or secondary to conditions such as systemic sclerosis or congenital heart disease. The condition exists in both adult and paediatric forms, which possess several similar characteristics. Adult and paediatric PAH can, however, be distinguished based on underlying pathology and the presence of age-specific conditions, some of which are related to poor lung development in children. Improved knowledge of vascular biology has led to the development of several PAH-specific therapies, which have demonstrated clinical benefits in adults, including improved exercise capacity and prolonged survival. Treatment data in paediatric PAH are scarce. Although limited, the existing data indicate that current treatments for paediatric PAH are well tolerated and effective, at least in the short- and medium-term. Nevertheless, the current guidelines for clinicians, which recommend use of the adult treatment algorithm in paediatric patients, appear justified when judged according to the available evidence. However, further randomised, controlled trials are necessary to increase the evidence base for treatment of paediatric PAH, especially in relation to age-specific conditions. At present, early initiation of treatment and combination pharmacological therapy may offer the most promising courses of action to improve outcomes in paediatric PAH.

  7. Iron deficiency in patients with idiopathic pulmonary arterial hypertension

    NARCIS (Netherlands)

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

    2014-01-01

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

  8. Genetics Home Reference: pulmonary arterial hypertension

    Science.gov (United States)

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

  9. The study of risk in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gerald Simonneau

    2012-09-01

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

  10. 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......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...

  11. 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...... likely includes the combination of vasodilatation and vasoconstriction in parallel. Arterial compliance; Central vascular filling; Chyperdynamic circulation; Kidney function, Nitric oxide; Blood pressure regulation; Renin–angiotensin–aldosterone system; Sympathetic nervous system; Vasodilatation...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  13. Genetics and genomics of pulmonary arterial hypertension.

    Science.gov (United States)

    Soubrier, Florent; Chung, Wendy K; Machado, Rajiv; Grünig, Ekkehard; Aldred, Micheala; Geraci, Mark; Loyd, James E; Elliott, C Gregory; Trembath, Richard C; Newman, John H; Humbert, Marc

    2013-12-24

    Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or

  14. Clinical classification in pediatric pulmonary arterial hypertension associated with congenital heart disease

    NARCIS (Netherlands)

    Zijlstra, Willemijn M H; Douwes, Johannes M; Ploegstra, Mark-Jan; Krishnan, Usha; Roofthooft, Marcel; Hillege, Hans L; Ivy, D Dunbar; Rosenzweig, Erika B; Berger, Rolf M F

    2016-01-01

    Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore

  15. Pathogenic Mechanisms of Pulmonary Arterial Hypertension

    Science.gov (United States)

    Chan, Stephen Y.; Loscalzo, Joseph

    2008-01-01

    Pulmonary arterial hypertension (PAH)1 is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease. PMID:17950310

  16. miR-223 reverses experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien

    2015-09-15

    Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.

  17. How Is Pulmonary Hypertension Treated?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Treated? Pulmonary hypertension (PH) has no cure. However, ... Types of Pulmonary Hypertension." ) Group 1 Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension (PAH) includes PH ...

  18. Update in pulmonary arterial hypertension.

    Science.gov (United States)

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

    2016-11-01

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

  19. Age, hypertension and arterial function.

    Science.gov (United States)

    McEniery, Carmel M; Wilkinson, Ian B; Avolio, Albert P

    2007-07-01

    1. Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross-sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age-related changes observed in peripheral arteries appear to be less marked. 2. The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3. Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4. Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end-product cross-links between proteins, such as collagen and elastin, hold substantial promise.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  1. Liver cirrhosis and arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Jens H Henriksen; Soren Moller

    2006-01-01

    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 vasopressin),and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators,and is most pronounced in the splanchnic area.This constitutes an effective (although relative)counterbalance to increased arterial 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 likely includes the combination of vasodilatation and vasoconstriction in parallel.

  2. Review of bosentan in the management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Eli Gabbay

    2008-01-01

    Full Text Available Eli Gabbay1, John Fraser2, Keith McNeil31Western Australian Lung Transplant Unit and Pulmonary Hypertension Service, Royal Perth Hospital, Western Australia, Australia; 2Critical Care Research Group, The Prince Charles Hospital, Rode Road, Chermside, Queensland, Australia; 3Transplant and Pulmonary Vascular Disease Unit, The Prince Charles Hospital, Rode Road, Chermside, Queensland, AustraliaAbstract: The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH. This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined.Keywords: bosentan, pulmonary arterial hypertension, review

  3. Role of oxidized lipids in pulmonary arterial hypertension

    Science.gov (United States)

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

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603

  4. Role of oxidized lipids in pulmonary arterial hypertension.

    Science.gov (United States)

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

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

  5. Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog.

    Science.gov (United States)

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

    2006-08-01

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

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

    Directory of Open Access Journals (Sweden)

    B.J.M. Mulder

    2010-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a serious complication of congenital heart disease (CHD. Without early surgical repair, around one-third of paediatric CHD patients develop significant PAH. Recent data from the Netherlands suggest that >4% of adult CHD patients have PAH, with higher rates in those with septal defects. A spectrum of cardiac defects is associated with PAH-CHD, although most cases develop as a consequence of large systemic-to-pulmonary shunts. Eisenmenger's syndrome, characterised by reversed pulmonary-to-systemic (right-to-left shunt, represents the most advanced form of PAH-CHD and affects as many as 50% of those with PAH and left-to-right shunts. It is associated with the poorest outcome among patients with PAH-CHD. 40 yrs ago, ∼50% of children with CHD requiring intervention died within the first year, and <15% survived to adulthood. Subsequent advances in paediatric cardiology have seen most patients with CHD survive to adulthood, with resulting shifts in the demographics of CHD and PAH-CHD. The number of adults presenting with CHD is increasing and, although mortality is decreasing, morbidity is increasing as older patients are at increased risk of arrhythmia, heart failure, valve regurgitation and PAH. Data show that probability of PAH increases with age in patients with cardiac defects.

  7. Drug-induced pulmonary arterial hypertension: a recent outbreak

    Directory of Open Access Journals (Sweden)

    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.

  8. Immune Mechanisms in Arterial Hypertension.

    Science.gov (United States)

    Wenzel, Ulrich; Turner, Jan Eric; Krebs, Christian; Kurts, Christian; Harrison, David G; Ehmke, Heimo

    2016-03-01

    Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

  9. Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir.

    Science.gov (United States)

    Renard, Sébastien; Borentain, Patrick; Salaun, Erwan; Benhaourech, Sanaa; Maille, Baptiste; Darque, Albert; Bregigeon, Sylvie; Colson, Philippe; Laugier, Delphine; Gaubert, Martine Reynaud; Habib, Gilbert

    2016-03-01

    Development of direct-acting antiviral agents against hepatitis C virus (HCV) has changed the management of chronic HCV infection. We report three cases of newly diagnosed or exacerbated pulmonary arterial hypertension (PAH) in patients treated with sofosbuvir. All patients had PAH-associated comorbidities (HIV coinfection in two, portal hypertension in one) and one was already being treated for PAH. At admission, all patients presented with syncope, World Health Organization functional class IV, right-sided heart failure, and extremely severe hemodynamic parameters. After specific PAH therapy, the clinical and hemodynamic properties for all patients were improved. Severity and acuteness of PAH, as well as chronology, could suggest a causal link between HCV treatment and PAH onset. We hypothesize that suppression of HCV replication promotes a decrease in vasodilatory inflammatory mediators leading to worsening of underlying PAH. The current report suggests that sofosbuvir-based therapy may be associated with severe PAH.

  10. Outcome of Pediatric Patients With Pulmonary Arterial Hypertension in the Era of New Medical Therapies

    NARCIS (Netherlands)

    van Loon, Rosa Laura E.; Roofthooft, Marcus T. R.; Delhaas, Tammo; van Osch-Gevers, Magdalena; ten Harkel, Arend D. J.; Strengers, Jan L. M.; Backx, Ad; Hillege, Hans L.; Berger, Rolf M. F.

    2010-01-01

    Little is known about the effects of "second-generation drugs" (prostanoids, endothelin receptor antagonists, 5-phosphodiesterase inhibitors) in children with pulmonary arterial hypertension (PAH). This study describes the outcome of a national cohort of children with PAH in an era when these drugs

  11. Growth in children with pulmonary arterial hypertension : a longitudinal retrospective multiregistry study

    NARCIS (Netherlands)

    Ploegstra, Mark-Jan; Ivy, D Dunbar; Wheeler, Jeremy G; Brand, Monika; Beghetti, Maurice; Rosenzweig, Erika B; Humpl, Tilman; Iriart, Xavier; Rouzic, Erwan Muros-Le; Bonnet, Damien; Berger, Rolf M F

    2016-01-01

    BACKGROUND: To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. METHODS: We did a retrospective longitudinal study of height and body-mass index in

  12. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study

    NARCIS (Netherlands)

    Coghlan, J.G.; Denton, C.P.; Grunig, E.; Bonderman, D.; Distler, O.; Khanna, D.; Muller-Ladner, U.; Pope, J.E.; Vonk, M.C.; Doelberg, M.; Chadha-Boreham, H.; Heinzl, H.; Rosenberg, D.M.; McLaughlin, V.V.; Seibold, J.R.

    2014-01-01

    OBJECTIVE: Earlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc), facilitates earlier treatment. The objective of this study was to develop the first evidence-based detection algorithm for PAH in SSc. METHODS: In this cross-sectional, intern

  13. Pulmonary arterial hypertension in congenital heart disease : An epidemiologic perspective from a Dutch registry

    NARCIS (Netherlands)

    Duffels, M. G. J.; Engelfriet, P. M.; Berger, R. M. F.; van Loon, R. L. E.; Hoendermis, E.; Vriend, J. W. J.; Bresser, P.; Mulder, B. J. M.; van der Velde, Enno T.

    2007-01-01

    Background: Pulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-topulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  15. The Molecular Genetics and Cellular Mechanisms Underlying Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Rajiv D. Machado

    2012-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards.

  16. Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Bonnet, Sebastien; Provencher, Steeve; Guignabert, Christophe; Perros, Frédéric; Boucherat, Olivier; Schermuly, Ralph Theo; Hassoun, Paul M; Rabinovitch, Marlene; Nicolls, Mark R; Humbert, Marc

    2016-09-20

    Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding. Although this is not unique to PAH, there is urgency for reducing the number of false positive signals in preclinical studies and optimizing the development of innovative therapeutic targets through performance of clinical trials based on more robust experimental data. The current review discusses the challenges and opportunities in preclinical research to foster drug development in PAH.

  17. Oral treprostinil for the treatment of pulmonary arterial hypertension.

    Science.gov (United States)

    de Lartigue, J

    2014-08-01

    Pulmonary arterial hypertension (PAH) is a rare yet progressive and life-threatening condition that, despite the availability of FDA-approved therapies, remains incurable. Prostacyclin analogues are a mainstay of therapy for patients with PAH, but in spite of demonstrated improvements in survival, exercise capacity and hemodynamics, these agents have been limited by poor pharmacokinetics and complex administration requirements. Treprostinil diolamine (Orenitram™; United Therapeutics) is a novel oral formulation that joins the approved parenteral and inhaled formulations (Remodulin® and Tyvaso®; United Therapeutics). It displays similar pharmacokinetic properties, while offering the potential for improved patient compliance through the convenience of oral dosing. Following the demonstration of improved exercise capacity as monotherapy in patients with de novo PAH (FREEDOM-M), treprostinil diolamine was recently approved by the FDA for the treatment of patients with WHO group 1 PAH and continues to be evaluated in a number of clinical trials in this patient population.

  18. Optimising the management of pulmonary arterial hypertension patients: emergency treatments

    Directory of Open Access Journals (Sweden)

    R. Naeije

    2010-09-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation.

  19. Capsaicin and arterial hypertensive crisis.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

    2010-10-08

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin.

  20. New therapies for arterial hypertension.

    Science.gov (United States)

    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.

  1. Comparison of clinical characteristics and survival on patients with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension during conventional therapy era and targeted therapy era

    Institute of Scientific and Technical Information of China (English)

    徐希奇

    2014-01-01

    Objective To compare the clinical characteristics and survival on Chinese patients with idiopathic pulmonary arterial hypertension(IPAH)and familiar pulmonary arterial hypertension(FPAH)during conventional therapy era and targeted therapy era.Methods IPAH and FPAH patients who were referred between Jan 1999and Oct 2004 in Fuwai Hospital were defined as conventional therapy era group(before 2005 no PAH-specific drug was available in China).All patients in this group

  2. Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?

    Science.gov (United States)

    Panagiotou, Marios; Peacock, Andrew J; Johnson, Martin K

    2015-09-01

    Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted.

  3. [Update arterial hypertension 2015].

    Science.gov (United States)

    Rickenbacher, Peter

    2015-04-22

    Hypertension, defined as office blood pressure of ≥140 mmHg systolic and/or ≥90 mmHg diastolic, is prevalent and one of the most important risk factors for disease and premature death. Diagnostic evaluation includes risk stratification regarding other cardiovascular risk factors, cardiovascular disease and asymptomatic organ damage. Currently, treatment is generally recommended with blood pressure ≥140/90 mmHg with the goal of reducing values below these limits also in high risk patients. Exceptions concern patients with advanced age or diabetes. Treatment involves lifestyle changes, anthypertensive drugs and in the future probably interventional techniques. This mini-review summarizes selected and practically relevant diagnostic and therapeutic aspects from recent international guidelines.

  4. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

    OpenAIRE

    Tselios K; Gladman DD; Urowitz MB

    2016-01-01

    Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, ON, Canada Abstract: Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (&...

  5. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

    Science.gov (United States)

    Laveneziana, Pierantonio; Garcia, Gilles; Joureau, Barbara; Nicolas-Jilwan, Fadia; Brahimi, Toufik; Laviolette, Louis; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Similowski, Thomas

    2013-03-01

    Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.

  6. Apoptosis-based therapy to treat pulmonary arterial hypertension

    Science.gov (United States)

    Suzuki, Yuichiro J.; Ibrahim, Yasmine F.; Shults, Nataliia V.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is rare, but patients who are diagnosed with this disease still suffer from a lack of satisfactory treatment strategies to prolong survival. While currently approved drugs for PAH have some benefits, these vasodilators only have limited efficacy for eliminating pulmonary vascular remodeling and reducing mortality. Thus, our laboratory has been exploring the use of aggressive drugs, which are capable of causing apoptotic cell death, to treat PAH. We have so far found that three classes of anti-tumor agents, including anthracyclines, taxanes, and proteasome inhibitors, are capable of reducing pulmonary vascular thickness in rats with PAH. These drugs kill cells in remodeled pulmonary vessels without affecting the normal, healthy pulmonary vasculature, revealing that proliferating vascular cells in PAH patients are more sensitive to drug-induced apoptosis compared to the differentiated phenotype that is physiologically important for smooth muscle contraction. Since many apoptosis-inducing drugs cause cardiotoxicity in cancer patients, and because PAH patients already have a weakened heart, we focus on finding biological mechanisms that may reverse pulmonary vascular remodeling without promoting cardiotoxicity. We found two agents, dexrazoxane and pifithrin-α, that selectively inhibit cardiac muscle apoptosis without affecting the drug-induced apoptosis of the proliferating pulmonary vascular cells. Thus, we propose that the addition of apoptosis-inducing drugs and cardioprotectants to PAH therapies may be effective in treating patients and preventing right heart failure.

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

    NARCIS (Netherlands)

    V.J.M. Baggen (Vivan J. M.); I. Leiner; M.C. Post (Martijn); A.P.J. van Dijk (Arie); J.W. Roos-Hesselink (Jolien); H. Boersma (Eric); J. Habets; G.T. Sieswerda (Gertjan)

    2016-01-01

    textabstractObjectives: To provide a comprehensive overview of all reported cardiac magnetic resonance (CMR) findings that predict clinical deterioration in pulmonary arterial hypertension (PAH). Methods: MEDLINE and EMBASE electronic databases were systematically searched for longitudinal studies p

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 pat

  9. Gender-related differences in pulmonary arterial hypertension targeted drugs administration.

    Science.gov (United States)

    Marra, Alberto M; Benjamin, Nicola; Eichstaedt, Christina; Salzano, Andrea; Arcopinto, Michele; Gargani, Luna; D Alto, Michele; Argiento, Paola; Falsetti, Lorenzo; Di Giosia, Paolo; Isidori, Andrea M; Ferrara, Francesco; Bossone, Eduardo; Cittadini, Antonio; Grünig, Ekkehard

    2016-12-01

    During the last 15 years, a real "paradigm-shift" occurred, due to the development of PAH-targeted drugs, leading to crucial improvements in symptoms, exercise capacity, hemodynamics and outcome of PAH patients. In order to describe differences regarding epidemiology and therapy in PAH according to gender, we performed a review of the available literature in "PubMed" and "Web of Science" databases. In order to find relevant articles, we combined each of the following the keywords "pulmonary arterial hypertension", "gender", "sex", "men", "woman", "male", "female", "phosphodiesterase inhibitors", "endothelin receptor antagonists", "prostanoids". While there is a substantial agreement among epidemiological studies in reporting an increased prevalence of pulmonary arterial hypertension (PAH) among women, male PAH patients are affected by a higher impairment of the right ventricular function and consequently experience poorer outcomes. With regards to PAH-targeted drug administration, endothelin receptor antagonists (ERAs) and prostacyclin analogues (PC) show better treatment results in female PAH patients, while phosphodiesterase-5 inhibitors (PD5-I) seem to exert a more beneficial effect on male patients. However, to date no clear consensus could be formed by the available literature, which is constituted mainly by retrospective studies. Females with PAH are more prone to develop PAH, while males experience poorer outcomes. Females PAH might benefit more from ERAs and PC, while males seem to have more beneficial effects from PD5-I administration. However, more research is warranted in order to assess the most effective treatment for PAH patients according to gender.

  10. Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Sakao, Seiichiro; Voelkel, Norbert F; Tanabe, Nobuhiro; Tatsumi, Koichiro

    2015-01-01

    Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

  11. Renal sympathetic denervation prevents the development of pulmonary arterial hypertension and cardiac dysfunction in dogs.

    Science.gov (United States)

    Hu, Wei; Yu, Sheng-Bo; Chen, Liao; Guo, Rui-Qiang; Zhao, Qing-Yan

    2015-08-01

    The renin-angiotensin-aldosterone system is activated in pulmonary arterial hypertension (PAH) patients, and this activation may have long-term negative effects on the progression of PAH. The purpose of this study was to evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the development of pulmonary arterial hypertension and cardiac dysfunction in dogs using two-dimensional speckle tracking imaging. Twenty-two dogs were randomly divided into three groups: control group (n = 7), PAH group (n = 8), and PAH + RSD group (n = 7). All dogs were assessed using two-dimensional speckle tracking imaging. The ventricular strain, ventricular synchrony, left ventricular (LV) twist, and torsion rate were analyzed to evaluate cardiac function. After 8 weeks, the right ventricular lateral longitudinal strain and the septum longitudinal strain were reduced in the PAH group compared with the control group (p dogs.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Federici, Chiara; Drake, Kylie M.; Rigelsky, Christina M.; McNelly, Lauren N.; Meade, Sirena L.; Comhair, Suzy A. A.; Erzurum, Serpil C.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a serious lung condition characterized by vascular remodeling in the precapillary pulmonary arterioles. We and others have demonstrated chromosomal abnormalities and increased DNA damage in PAH lung vascular cells, but their timing and role in disease pathogenesis is unknown. Objectives: We hypothesized that if DNA damage predates PAH, it might be an intrinsic cell property that is present outside the diseased lung. Methods: We measured DNA damage, mutagen sensitivity, and reactive oxygen species (ROS) in lung and blood cells from patients with Group 1 PAH, their relatives, and unrelated control subjects. Measurements and Main Results: Baseline DNA damage was significantly elevated in PAH, both in pulmonary artery endothelial cells (P < 0.05) and peripheral blood mononuclear cells (PBMC) (P < 0.001). Remarkably, PBMC from unaffected relatives showed similar increases, indicating this is not related to PAH treatments. ROS levels were also higher (P < 0.01). DNA damage correlated with ROS production and was suppressed by antioxidants (P < 0.001). PBMC from patients and relatives also showed markedly increased sensitivity to two chemotherapeutic drugs, bleomycin and etoposide (P < 0.001). Results were consistent across idiopathic, heritable, and associated PAH groups. Conclusions: Levels of baseline and mutagen-induced DNA damage are intrinsically higher in PAH cells. Similar results in PBMC from unaffected relatives suggest this may be a genetically determined trait that predates disease onset and may act as a risk factor contributing to lung vascular remodeling following endothelial cell injury. Further studies are required to fully characterize mutagen sensitivity, which could have important implications for clinical management. PMID:25918951

  14. Pulmonary arterial hypertension associated with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Michele D'Alto

    2012-12-01

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

  15. 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.

  16. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    Science.gov (United States)

    Papathanasiou, Athanasios; Nakos, George

    2015-11-04

    Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of increased endothelin-1 activity and impaired nitric oxide-dependent vasodilation

  17. Pulmonary arterial hypertension: the burden of disease and impact on quality of life.

    Science.gov (United States)

    Delcroix, Marion; Howard, Luke

    2015-12-01

    Pulmonary arterial hypertension (PAH) is a debilitating disease that pervades all aspects of a patient's daily life. It is also increasingly acknowledged that the burden of PAH extends to older patients and carers. Until recently, the adverse effect of disease symptoms on the physical, emotional and social factors governing patient health-related quality of life (HRQoL) remained largely unrecognised. With a shift in therapeutic objectives to longer term improvements and HRQoL benefits, clinical trials now frequently include HRQoL measures as study end-points. Most HRQoL instruments used in patients with PAH are generic or non-disease-specific questionnaires and therefore may not accurately capture PAH disease burden. New PAH-specific HRQoL instruments currently undergoing validation include emPHasis-10 and Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Using various HRQoL measures, pharmacological therapies have been shown to improve HRQoL in patients with PAH. Patients also derive HRQoL benefits from nonpharmacological strategies, which include the emotional support provided by multidisciplinary care and support groups that is fundamental to patient wellbeing. Looking to the future, validated PAH-specific HRQoL instruments together with dedicated guidelines and procedures are essential to support the translation of HRQoL scores to the clinic, thus enabling a holistic treatment approach to the management of patients with PAH.

  18. Screening for pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2009-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Francisca Gavilanes

    2014-12-01

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

  20. Early detection and management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Marc Humbert

    2012-12-01

    Full Text Available The long-term prognosis for patients with pulmonary arterial hypertension (PAH remains poor, despite advances in treatment options that have been made in the past few decades. Recent evidence suggests that World Health Organization functional class I or II patients have significantly better long-term survival rates than patients in higher functional classes, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programmes play an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH (i.e. those with systemic sclerosis or sickle cell disease, although current guidelines only recommend annual echocardiographic screening in symptomatic patients. This article reviews the currently available screening programmes, including their limitations, and describes alternative screening approaches that may identify more effectively those patients who require right heart catheterisation for a definitive PAH diagnosis.

  1. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    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...... the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those 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...

  2. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    Science.gov (United States)

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

    2016-10-01

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

  3. Evaluating health-related quality of life, work ability, and disability in pulmonary arterial hypertension: an unmet need.

    Science.gov (United States)

    Rubenfire, Melvyn; Lippo, Giuseppina; Bodini, Bruno D; Blasi, Francesco; Allegra, Luigi; Bossone, Eduardo

    2009-08-01

    To our knowledge, there are no specific and validated measures of quality of life (QoL) or degree of disability for pulmonary arterial hypertension (PAH). A review of the literature shows that, with the exception of one recently designed specifically for pulmonary hypertension, QoL questionnaires used in PAH studies are generic measures. These are selected because of shared symptoms that do not necessarily correlate well with functional or physiologic measures and have not been validated for applicability in PAH. In this review, we present the available QoL tools for pulmonary artery hypertension and describe the need for more specific instruments that consider the physical and emotional implications of the diseases associated with PAH and the impact of various treatment options. We also discuss the impact of PAH on work ability and the need for provisions to address medical disability status and Social Security benefit status.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Epistatic interactions in idiopathic pulmonary arterial hypertension

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    Shivani Vadapalli

    2012-01-01

    Full Text Available Background : Idiopathic pulmonary arterial hypertension (IPAH is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR analysis is a statistical method used to identify gene-gene interaction or epistasis and gene-environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. Aim: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. Materials and Methods: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2. MDR method was adopted to determine gene-gene interactions that increase the risk of IPAH. Results : With MDR method, the single-locus model of 5HTT (L/S polymorphism and the combination of 5HTT(L/S, EDN1(K198N, and NOS3(G894T polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. Conclusion: MDR method can be useful in understanding the role of epistatic and gene-environmental interactions in pathogenesis of IPAH.

  6. Endothelial GATA-6 Deficiency Promotes Pulmonary Arterial Hypertension

    Science.gov (United States)

    Ghatnekar, Angela; Chrobak, Izabela; Reese, Charlie; Stawski, Lukasz; Seta, Francesca; Wirrig, Elaine; Paez-Cortez, Jesus; Markiewicz, Margaret; Asano, Yoshihide; Harley, Russell; Silver, Richard; Feghali-Bostwick, Carol; Trojanowska, Maria

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by pulmonary vasculopathy with elevation of pulmonary artery pressure, often culminating in right ventricular failure. GATA-6, a member of the GATA family of zinc-finger transcription factors, is highly expressed in quiescent vasculature and is frequently lost during vascular injury. We hypothesized that endothelial GATA-6 may play a critical role in the molecular mechanisms underlying endothelial cell (EC) dysfunction in PAH. Here we report that GATA-6 is markedly reduced in pulmonary ECs lining both occluded and nonoccluded vessels in patients with idiopathic and systemic sclerosis-associated PAH. GATA-6 transcripts are also rapidly decreased in rodent PAH models. Endothelial GATA-6 is a direct transcriptional regulator of genes controlling vascular tone [endothelin-1, endothelin-1 receptor type A, and endothelial nitric oxide synthase (eNOS)], pro-inflammatory genes, CX3CL1 (fractalkine), 5-lipoxygenease-activating protein, and markers of vascular remodeling, including PAI-1 and RhoB. Mice with the genetic deletion of GATA-6 in ECs (Gata6-KO) spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, and these features are further exacerbated in response to hypoxia. Furthermore, innate immune cells including macrophages (CD11b+/F4/80+), granulocytes (Ly6G+/CD45+), and dendritic cells (CD11b+/CD11c+) are significantly increased in normoxic Gata6-KO mice. Together, our findings suggest a critical role of endothelial GATA-6 deficiency in development and disease progression in PAH. PMID:23583651

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

    Directory of Open Access Journals (Sweden)

    Jeremy A Falk

    2010-04-01

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

  8. [Arterial hypertension secondary to endocrine disorders].

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Macitentan: An important addition to the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Anjan Khadka

    2015-01-01

    Full Text Available Macitentan is an orphan drug for the treatment of pulmonary arterial hypertension (PAH. Endothelin-1 (ET-1 plays a critical role of pathophysiology of PAH. Macitentan, a new dual endothelin receptor antagonist, has reportedly improved prognosis of PAH patients by delaying the progression of disease. It prevents the binding of ET-1 to both endothelin A (ET A and endothelin B (ET B receptors. Macitentan displays higher efficacy, lesser adverse effects and drug interactions. It has completed phase III trials in 2012 for treatment of PAH and has been tried for ischemic digital ulcers in systemic sclerosis, recurrent glioblastoma and combination with chemotherapeutic agents against various cancers. Safety data for macitentan were obtained primarily from a placebo-controlled clinical study in 742 patients with PAH. The Food and Drug Administration (FDA approved the drug on 13 October 2013. It is an important addition to long-term treatment of PAH.

  11. Treatment of Vasodilator-resistant Mixed Connective Tissue Disease-associated Pulmonary Arterial Hypertension with Glucocorticoid and Cyclophosphamide.

    Science.gov (United States)

    Sugawara, Eri; Kato, Masaru; Hisada, Ryo; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-01-01

    Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present case was a 34-year-old woman with MCTD-associated PAH (WHO functional class IV) who was resistant to a combination of three vasodilators. Afterwards, she was treated with glucocorticoid and cyclophosphamide. This case suggested the potential benefit of immunosuppressants in patients with severe MCTD-associated PAH.

  12. Tinnitus and arterial hypertension: a systematic review.

    Science.gov (United States)

    Figueiredo, Ricardo Rodrigues; de Azevedo, Andréia Aparecida; Penido, Norma de Oliveira

    2015-11-01

    Tinnitus is considered a multi-factorial symptom. Arterial hypertension has been cited as a tinnitus etiological factor. To assess the scientific evidence on the associations between arterial hypertension and tinnitus. A systematic review was performed using PubMed, ISI Web, Lilacs and SciELO scientific databases. This review included articles published in Portuguese, Spanish, French and English correlating tinnitus with hypertension. Letters to editors and case reports were excluded. A total of 424 articles were identified, of which only 20 met the inclusion criteria. Studies that analyzed the incidence of hypertension in tinnitus patients tended to show an association, while those that evaluated the incidence of tinnitus in hypertensive patients did not. There is evidence of an association between tinnitus and hypertension, although a cause and effect relationship is uncertain. Changes in the cochlear microcirculation, resulting in hearing loss, may be an adjuvant factor in tinnitus pathophysiology.

  13. New trial designs and potential therapies for pulmonary artery hypertension.

    Science.gov (United States)

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2013-12-24

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.

  14. 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

  15. Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood

    NARCIS (Netherlands)

    Harrison, RE; Berger, R; Haworth, SG; Tulloh, R; Mache, CJ; Morrell, NW; Aldred, MA; Trembath, RC

    2005-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a potentially fatal vasculopathy that can develop at any age. Adult-onset disease has previously been associated with mutations in BMPR2 and ALK-1. Presentation in early life may be associated with congenital heart disease but frequently is idiopa

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

    NARCIS (Netherlands)

    Riel, A.C. van; Schuuring, M.J.; Hessen, I.D. van; Zwinderman, A.H.; Cozijnsen, L.; Reichert, C.L.; Hoorntje, J.C.A.; Wagenaar, L.J.; Post, M.C.; Dijk, A.P.J. van; Hoendermis, E.S.; Mulder, B.J.; Bouma, B.J.

    2014-01-01

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

  17. Epoprostenol sodium for treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Saito Y

    2015-05-01

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

  18. Hemodynamic response to treatment of iron deficiency anemia in pulmonary arterial hypertension: longitudinal insights from an implantable hemodynamic monitor

    OpenAIRE

    Mehmood, Muddassir; Agarwal, Richa; Raina, Amresh; Correa-Jaque, Priscilla; Benza, Raymond L.

    2016-01-01

    Despite new therapeutic options, pulmonary arterial hypertension (PAH) remains a progressive disease associated with substantial morbidity and mortality. As such, additional strategies for monitoring and adjunctive management of this disease are important. A 59-year-old woman with scleroderma-associated PAH received an implantable hemodynamic monitor (IHM) as part of a research protocol at our institution. Pulmonary artery pressures, heart rate, and cardiac output (sensor-based algorithm) wer...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-15

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

  20. Initial experience with tadalafil in pediatric pulmonary arterial hypertension.

    Science.gov (United States)

    Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar

    2012-06-01

    This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-18

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

  2. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Henrie AM

    2015-11-01

    Full Text Available Adam M Henrie, James J Nawarskas, Joe R Anderson College of Pharmacy, University of New Mexico, Albuquerque, NM, USA Abstract: Pulmonary arterial hypertension (PAH is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phosphodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH. Keywords: tadalafil, phosphodiesterase-5 inhibitor, pulmonary arterial hypertension

  3. Secondary Headaches Attributed to Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Farhad Assarzadegan

    2013-07-01

    Full Text Available Mild (140 to 159/90 to 99 mmHg or moderate (160 to 179/100 to 109 mmHg chronic arterial hypertension does not appear to cause headache. Whether moderate hypertension predisposes patients to headache at all remains controversial, but there is little evidence that it does. Ambulatory blood pressure monitoring in patients with mild and moderate hypertension has shown no convincing relationship between blood pressure fluctuations over a 24-hour period and presence or absence of headache. However, headaches are associated to various disorders that lead to abrupt, severe, and paroxysmal elevations in blood pressure. In this paper, the secondary headaches attributed to acute crises of hypertension and the criteria for diagnosing each of them have been reviewed. These are headaches attributed to pheochromocytoma, hypertensive crisis without encephalopathy, hypertensive encephalopathy, pre-eclampsia, eclampsia, and acute pressure response to exogenous agents.

  4. Diffuse Pulmonary Arteriovenous Fistulas With Pulmonary Arterial Hypertension: Case Report and Review.

    Science.gov (United States)

    Jiang, Rong; Gong, Su-Gang; Pudasaini, Bigyan; Zhao, Qin-Hua; Wang, Lan; He, Jing; Liu, Jin-Ming

    2016-04-01

    Pulmonary arteriovenous fistulas (PAVFs) are rare. Diffuse type PAVFs with pulmonary arterial hypertension (PAH) are even rarer and can elude anatomy imaging like a plain chest film or a computed tomography. The rapid blood flow that ensues due to lack of a capillary bed leads to various degrees of ischemia depending on the number and size of the PAVF. This is a case report of diffuse PAVF in a patient with PAH.This case report describes a patient with recurrent hemoptysis and chest pain. Systemic examination was unremarkable except for P2 attenuation on auscultation. Echocardiograghy showed confirmed pulmonary hypertension with mild dilation of right atrium and ventricle and a tricuspid regurgitation pressure gradient of 40 mm Hg and ruled out congenital heart diseases. Right heart catheterization revealed precapillary PAH with mean pulmonary arterial pressure of 88 mm Hg. Pulmonary angiography showed enlarged pulmonary arterial trunk and diffuse spiral tortuous pulmonary arterial branches indicting diffuse PAVFs. The patient was diagnosed as PAH and began treatment of 25 mg tid of sildenafil.The case highlights a rare and unique presentation of PAH.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Integrated care and optimal management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    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

  7. Medical treatment update on pulmonary arterial hypertension.

    Science.gov (United States)

    Enderby, Cher Y; Burger, Charles

    2015-09-01

    Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.

  8. Anesthetic Management of Pediatric Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Mediha Turktan

    2015-06-01

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

  9. Recent trends in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Rajagopalan Natarajan

    2011-01-01

    Full Text Available Pulmonary hypertension is a serious and unrelenting pulmonary vascular disorder that affects the functional quality of patients and significantly decreases their life span. If diagnosed early, with the number of new therapeutic options that are available, a better quality of life can be provided for a protracted length of time. It is likely that the available treatment will change the natural course of the disease and perhaps prolong survival. As symptoms are often subtle in the early stages of the disease it is imperative that physicians are aware of the manifestations of this condition. A thorough investigation of patients suspected of this condition is essential so that appropriate treatment can be initiated promptly. The routine workup of a patient suspected to have pulmonary hypertension could easily be carried out in any well-equipped peripheral hospital in many affluent and advanced countries. However, it must be mentioned that in some less advanced countries the necessary work up can only be done in major teaching hospitals. Both pulmonologists and cardiologists should be aware of the pathophysiology of pulmonary arterial hypertension, the workup and the treatment options that are available. Patients with refractory pulmonary hypertension should be referred to these research centers for enrolment into any ongoing drug trials as well as for evaluation for heart−lung, single lung, or double lung transplantation. This paper is primarily aimed at pulmonologists and cardiologists taking care of these patients. Unless indicated otherwise this paper mainly deals with WHO group 1 pulmonary hypertension which is designated pulmonary arterial hypertension. Extensive review of the literature spanning the last 30 years was made through Medline using titles such as primary pulmonary hypertension, pulmonary arterial hypertension, secondary pulmonary hypertension, and pulmonary vascular diseases.

  10. 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.

  11. 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...

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

    Science.gov (United States)

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

    2010-04-01

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

  13. Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

    Science.gov (United States)

    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.

  14. Pulmonary arterial hypertension in idiopathic inflammatory myopathies: Data from the French pulmonary hypertension registry and review of the literature.

    Science.gov (United States)

    Sanges, Sébastien; Yelnik, Cécile M; Sitbon, Olivier; Benveniste, Olivier; Mariampillai, Kuberaka; Phillips-Houlbracq, Mathilde; Pison, Christophe; Deligny, Christophe; Inamo, Jocelyn; Cottin, Vincent; Mouthon, Luc; Launay, David; Lambert, Marc; Hatron, Pierre-Yves; Rottat, Laurence; Humbert, Marc; Hachulla, Eric

    2016-09-01

    Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients.All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH.Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment.By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06).Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone.Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement, peripheral

  15. 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.

  16. Non-congenital heart disease associated pediatric pulmonary arterial hypertension

    OpenAIRE

    Ivy, D D; Feinstein, J. A.; Humpl, T; Rosenzweig, E. B.

    2009-01-01

    Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, he...

  17. [Drugs: an underestimated cause of arterial hypertension].

    Science.gov (United States)

    Serveaux, Marianne; Burnier, Michel; Pruijm, Menno

    2014-09-10

    In Switzerland, as in other Occidental countries, the prevalence of arterial hypertension (AHT) in the adult population is around 30-40%. Among the causes of secondary AHT, drug induced hypertension is sometimes omitted. Many molecules can induce AHT or worsen it due to an interaction with anti hypertensive drugs. Among these, NSAIDs and anti depressants, widely prescribed, should be used with caution, particularly in patients at risk, namely: those with preexisting AHT, the elderly, or patients suffering from kidney disease, diabetes, and/or heart failure. Increases in blood pressure have also been described with anti-vascular endothelial growth factor (VEGF) drugs, used in the treatment of (metastatic) cancer. A thorough anamnesis of drugs, including over the counter ones, should be performed in every hypertensive patient, and can avoid cumbersome and unnecessary investigations and therapy.

  18. Survey of polycyclic aromatic hydrocarbons (PAHs) in arterial street air of Hangzhou

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The presence of particulate and vapor PAHs, SO2 and Nox and other interrelated conditions (temperature, traffic intensity and wind velocity) were investigated in the arterial street air of Hangzhou. The concentration of the nine PAHs in the air was mean to 11.7 μg/m3, and the content of benzo(a)pyrene was up to 0.108 μg/m3. The contents of PAHs in the sampling sites were in good relation to the traffic intensity, and would be also affected by the terrain and meteorological conditions. The occurrences of PAHs in ambient air were mainly affected by their physical, chemical characters and temperature. The three- and four-ring PAHs (MW>228) mainly existed in the vapor phase and the five-ring PAHs (MW>228) existed predominately in the particulate phase. The fraction of vapor PAHs in the total nine PAHs was 84.2% in the air of the sampling sites. In the morning and evening, the concentrations of PAHs in the arterial street air were higher than that on the noon and the diurnal variation of PAHs was similar to that of the traffic gas NOx. A conclusion would be drawn that the major source of PAHs in the arterial street air was the traffic. And the results indicated that 75% of BaP would come from traffic source and remaining 25% of BaP would come from non-traffic source.

  19. Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension.

    Science.gov (United States)

    de Raaf, Michiel Alexander; Beekhuijzen, Manon; Guignabert, Christophe; Vonk Noordegraaf, Anton; Bogaard, Harm Jan

    2015-08-15

    The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). This review describes the effects of ERA's in PAH pathobiology and cardiopulmonary fetal development. While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient.

  20. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    Science.gov (United States)

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Pugliese SC

    2016-01-01

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

  3. Long-term effects with ambrisentan monotherapy in patients with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    文莉

    2014-01-01

    Objective To investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension(PAH).Methods Patients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10,2011 and August 30,2012for at least 6 months were enrolled.The efficacy endpoints were changes in exercise capacity,World Health Organization(WHO)functional class and N-terminal probrain natriuretic peptide(NT-pro BNP)level,echocardiographic parameters.The safety endpoint was the safety of long-term ambrisentan administration,as defined by

  4. A review of sitaxsentan sodium in patients with pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Aaron B Waxman

    2007-03-01

    Full Text Available Aaron B WaxmanDepartment of Internal Medicine, Pulmonary Critical Care Unit, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USAAbstract: Pulmonary arterial hypertension (PAH is a life threatening, progressive condition which eventually leads to fatal right heart failure. Endothelin-1 (ET-1, a potent vasoconstrictor peptide, is increased in the pulmonary arteries of patients with pulmonary hypertension. Endothelin-1 acts through the stimulation of 2 subtypes of receptors (endothelin receptor subtypes A [ETA] and B [ETB]. In PAH patients, ETRAs block the deleterious vasoconstrictor effects of ET-1, and ETRA treatment in PAH patients has been shown to be safe and efficacious. Sitaxsentan is an orally active, highly ETA selective ETRA that, in clinical trials, has demonstrated improvements in exercise capacity, functional class and hemodynamics in PAH patients. Sitaxsentan has been shown to be safe, well tolerated, and associated with a lower incidence of liver toxicity than other approved ETRAs.Keywords: endothelin receptor antagonist, endothelin receptor inhibitor, endothelin A, sitaxsentan, pulmonary hypertension, endothelin

  5. 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...

  6. Immunity in arterial hypertension: associations or causalities?

    Science.gov (United States)

    Anders, Hans-Joachim; Baumann, Marcus; Tripepi, Giovanni; Mallamaci, Francesca

    2015-12-01

    Numerous studies describe associations between markers of inflammation and arterial hypertension (aHT), but does that imply causality? Interventional studies that reduce blood pressure reduced also markers of inflammation, but does immunosuppression improve hypertension? Here, we review the available mechanistic data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever the primary cause of aHT. Innate and adaptive immunity get involved once hypertension has caused vascular wall injury as immunity is a modifier of endothelial dysfunction and vascular wall remodelling. As vascular remodelling progresses, immunity-related mechanisms can become significant cofactors for cardiovascular (CV) disease progression; vice versa, suppressing immunity can improve hypertension and CV outcomes. Innate and adaptive immunity both contribute to vascular wall remodelling. Innate immunity is driven by danger signals that activate Toll-like receptors and other pattern-recognition receptors. Adaptive immunity is based on loss of tolerance against vascular autoantigens and includes autoreactive T-cell immunity as well as non-HLA angiotensin II type 1 receptor-activating autoantibodies. Such processes involve numerous other modulators such as regulatory T cells. Together, immunity is not causal for hypertension but rather an important secondary pathomechanism and a potential therapeutic target in hypertension.

  7. Early Diagnosis of Rare Diseases with a Focus on Pulmonary Arterial Hypertension: A Narrative Review

    OpenAIRE

    Bonaguro, Russell

    2015-01-01

    Health outcomes for rare diseases can be greatly affected by timely diagnosis.This paper presents a narrative review of current literature on rare diseases, with a focuson Pulmonary Arterial Hypertension (PAH), to identify needs for early diagnosisinitiatives. The review assessed: what needs to be done, what is currently being done,and what are the approaches or change theories that underlie these initiatives.Literature from online key-word searches included academic articles pertaining todia...

  8. Safety and tolerability considerations in the use of sildenafil for children with pulmonary arterial hypertension

    OpenAIRE

    Dodgen AL; Hill KD

    2015-01-01

    Andrew L Dodgen,1 Kevin D Hill1,2 1Department of Pediatrics, Duke University Medical Center, 2Duke Clinical Research Institute, Durham, NC, USA Abstract: Sildenafil is a phosphodiesterase type-5 inhibitor approved for treatment of pulmonary arterial hypertension (PAH) in adults. Data from pediatric trials demonstrate a similar acute safety profile to the adult population but have raised concerns regarding the safety of long-term use in children. Interpretation of these trials remains controve...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Peptide-micelle Hybrids Containing Fasudil for Targeted Delivery to the Pulmonary Arteries and Arterioles to Treat PAH

    Science.gov (United States)

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

    2017-01-01

    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 DSPE-PEG 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, respectively. CAR-micelles containing fasudil had an entrapment efficiency of ∼58%, showed controlled release of the drug, and were monodispersed with an average size of ∼14nm. NMR 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 ∼1.7-fold and extended the drug half-life by ∼5-fold. 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. PMID:25266507

  12. Evidence for the Involvement of Type I Interferon in Pulmonary Arterial Hypertension

    Science.gov (United States)

    George, Peter M.; Oliver, Eduardo; Dorfmuller, Peter; Dubois, Olivier D.; Reed, Daniel M.; Kirkby, Nicholas S.; Mohamed, Nura A.; Perros, Frederic; Antigny, Fabrice; Fadel, Elie; Schreiber, Benjamin E.; Holmes, Alan M.; Southwood, Mark; Hagan, Guy; Wort, Stephen J.; Bartlett, Nathan; Morrell, Nicholas W.; Coghlan, John G.; Humbert, Marc; Zhao, Lan; Mitchell, Jane A.

    2014-01-01

    Rationale Evidence is increasing of a link between interferon (IFN) and pulmonary arterial hypertension (PAH). Conditions with chronically elevated endogenous IFNs such as systemic sclerosis are strongly associated with PAH. Furthermore, therapeutic use of type I IFN is associated with PAH. This was recognized at the 2013 World Symposium on Pulmonary Hypertension where the urgent need for research into this was highlighted. Objective To explore the role of type I IFN in PAH. Methods and Results Cells were cultured using standard approaches. Cytokines were measured by ELISA. Gene and protein expression were measured using reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemistry. The role of type I IFN in PAH in vivo was determined using type I IFN receptor knockout (IFNAR1−/−) mice. Human lung cells responded to types I and II but not III IFN correlating with relevant receptor expression. Type I, II, and III IFN levels were elevated in serum of patients with systemic sclerosis associated PAH. Serum interferon γ inducible protein 10 (IP10; CXCL10) and endothelin 1 were raised and strongly correlated together. IP10 correlated positively with pulmonary hemodynamics and serum brain natriuretic peptide and negatively with 6-minute walk test and cardiac index. Endothelial cells grown out of the blood of PAH patients were more sensitive to the effects of type I IFN than cells from healthy donors. PAH lung demonstrated increased IFNAR1 protein levels. IFNAR1−/− mice were protected from the effects of hypoxia on the right heart, vascular remodeling, and raised serum endothelin 1 levels. Conclusions These data indicate that type I IFN, via an action of IFNAR1, mediates PAH. PMID:24334027

  13. Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

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    Yuhei eNishimura

    2016-06-01

    Full Text Available Pulmonary arterial hypertension (PAH is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80 and anterior gradient 2 genes was significantly increased in the five datasets, whereas expression of SMAD family member 6 and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1 expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin-1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we

  14. 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

  15. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension.

    Science.gov (United States)

    Lang, Irene M; Gaine, Sean P

    2015-12-01

    Pulmonary arterial hypertension (PAH) is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.

  16. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Irene M. Lang

    2015-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.

  17. 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.

  18. [New trial designs and potential therapies for pulmonary artery hypertension].

    Science.gov (United States)

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2014-10-01

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial I concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH. (J Am Coil Cardiol 2013;62:D82-91) ©2013 by the American College of Cardiology Foundation.

  19. Hemodynamic variables and clinical features correlated with serum uric acid in patients with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Serum uric acid (UA), the final product of purine degradation, has been proposed to be a marker for the severity and a possible predictor of mortality in patients with pulmonary arterial hypertension (PAH). The objectives of this study were to elucidate whether serum UA level correlates with the clinical features and the hemodynamic variables in Chinese patients with PAH and to compare the difference of the correlates in patients associated with different etiologies. Methods Serum UA was assessed in 228 patients with three types of PAH (idiopathic PAH (IPAH), congenital heart disease related PAH (CHD-PAH) and connective tissue disease related PAH (CTD-PAH)) together with other clinical features. After the individualized treatment for at least 6 months, the UA levels and clinical features were re-evaluated in 88 patients. Results Serum UA was significantly elevated in patients with PAH compared with age-matched control subjects ((350.40±108.73) μmol/L vs (266.91±81.38) μmol/L), P<0.001). Serum UA negatively correlated with cardiac output and mixed venous saturation (SvO) in all three types of PAH (all P<0.05), positively correlated with the size of right ventricle in IPAH (P=0.002) and CTD-PAH (P=0.013) patients and with pulmonary vascular resistance just in CTD-PAH patients (P=0.001). Serum UA significantly decreased from (365.80±120.46) μmol/L to (333.67±117.56) μmol/L in 88 patients (P=0.006) with vasodilator therapy for at least 6 months, accompanied with a reduction in pulmonary vascular resistance from (15.13±6.96) Woods unit to (12.00±5.04) Woods unit (P=0.001) and an increase in cardiac output from (2.63±0.98) L/min to (3.08±1.04) L/min (P=0.005). Conclusions Serum UA increases in proportion to the clinical severity of all the three types of PAH, especially the CTD-PAH had a stronger correlations compared with IPAH and CHD-PAH. The serum UA levels also could partly reflect the response to the treatment in patients with PAH.

  20. Radioimmunoassay in the diagnosis of arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Olejnik, V.A.; Yakovlev, A.A.; Yugrinov, O.G.; Markov, V.V. (Kievskij Nauchno-Issledovatel' skij Inst. Ehndokrinologii i Obmena Veshchestv (Ukrainian SSR))

    1984-11-01

    The paper is concerned with the results of a study of the aldosterone concentration and renin activity, the general level of catecholamines and their fractions in the peripheral blood and blood taken at selective venography from the vena cava inferior, renal and adrenal veins of 108 patients with hypertension, aldosteroma and idiopathic hyperaldosteronism, adrenal and extraadrenal pheochromocytoma, renovascular and renoparenchymatous arterial hypertension. The aldosterone concentration and renin activity were determined with radioimmunoassay, and the general content of catecholamines and their fractions with a radioenzymatic method using standard kits. It has been shown that the radioimmunoassay to determine the aldosterone concentration and renin activity makes possible differential diagnosis of hypertension, aldosteroma, idiopathic and secondary hyperaldosteronism. A considerable increase in the blood plasma renin activity on the affected side was revealed in the patients with renovascular hypertension, and in renoparenchymatous hypertension it was equal in both renal veins. The study of the total content of catecholamines and their fractions in the blood from different parts of the venous system can be used for topical diagnosis of adrenal and extraadrenal pheochromocytoma.

  1. Early teatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression

    Institute of Scientific and Technical Information of China (English)

    王晓林

    2014-01-01

    Objective To investigate the effect of early treatment with hepatocyte growth factor(HGF)on the cytokine expression and pulmonary artery,right ventricular(RV)remodeling in the rat model of pulmonary artery hypertension(PAH).Methods The rat model of PAH was produced by injecting monocrotaline,and the model rats were randomly divided into empty adenovirus transfection group(MCT group,n=10)and HGF gene transfection group(HGF group,n=10).Another group of rats served as the Sham operation group(Sham group n=10).After 4 weeks of HGF gene transfection,the histological sections of the lungs and right ventricular(RV)

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

    Directory of Open Access Journals (Sweden)

    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.

  3. [Resistant arterial hypertension and coarctation of the aorta].

    Science.gov (United States)

    Martínez-Quintana, Efrén; Rossique-Delmas, Pilar; Rodríguez-González, Fayna

    2014-01-01

    Coarctation of the aorta accounts for around 5 percent of all congenital heart defects. Many of these patients develop arterial hypertension, and occasionally resistant arterial hypertension, despite adequate correction. This may lead to potentially fatal complications such as heart failure, aortic dissection, cerebrovascular events, or myocardial infarction. Therefore, a correct diagnosis must be made and an appropriate treatment started to reduce arterial hypertension, arteriosclerotic vascular disease, as well as the increased risk of cardiovascular morbidity and mortality.

  4. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

    Directory of Open Access Journals (Sweden)

    Brian Casserly

    2009-11-01

    Full Text Available Brian Casserly, James R KlingerDivision of Pulmonary and Critical Care Medicine, The Memorial Hospital of Rhode Island, Pawtucket, RI, Rhode Island Hospital, Providence, RI, Alpert Medical School of Brown University, Providence, RI, USAAbstract: B-type natriuretic peptide (BNP is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP and pulmonary vascular resistance (PVR in patients with pulmonary arterial hypertension (PAH. Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease.Keywords: brain natriuretic peptide, pulmonary artery hypertension

  5. Lung Transplantation for Pulmonary Hypertension

    Science.gov (United States)

    ... the page. Answers about Lung Transplantation for PULMONARY HYPERTENSION Part One: Overview From the development of epoprostenol ... decades, expansion of medical treatment of pulmonary arterial hypertension (PAH) has improved survival and quality of life ...

  6. Right heart function during simulated altitude in patients with pulmonary arterial hypertension

    Science.gov (United States)

    Seccombe, Leigh M; Chow, Vincent; Zhao, Wei; Lau, Edmund M T; Rogers, Peter G; Ng, Austin C C; Veitch, Elizabeth M; Peters, Matthew J; Kritharides, Leonard

    2017-01-01

    Objective Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Methods Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. Results The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Conclusions Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function. PMID:28123765

  7. [Novel immunopathological approaches to pulmonary arterial hypertension].

    Science.gov (United States)

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.

  8. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

    Directory of Open Access Journals (Sweden)

    M. L. Handoko

    2010-03-01

    Full Text Available Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH. At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article. Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that "left" and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF therapies for PAH, based on currently available literature. As in LHF, the sympathetic nervous system and the renin–angiotension–aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensin-converting enzyme inhibition or β-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well. In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials.

  9. Riociguat as a treatment regime for pulmonary arterial hypertension: a review.

    Science.gov (United States)

    Narang, Bawneet K; Roy, Subhajit; Sharma, Rajiv; Singh, Virender; Rawal, Ravindra K

    2015-01-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition distinguished by elevated pressure of pulmonary arteries and increased vascular resistance. The management of patients with PAH and CTEPH has advanced rapidly over last decade but despite the progress in the treatment, the survival of suffering patients remain unsatisfactory and there is no cure for the diseases. However, surgery is not a first choice for patients. Furthermore, some patients who undergo surgery have persistent pulmonary hypertension (HTN) as a side effect after surgery. Therefore, the search for an "ideal" therapy still goes on and it lead to the approval of riociguat as a potential agent for the treatment. It acts directly on soluble guanylate cyclase, exciting the enzyme, and elevating sensitivity to lower levels of NO. Riociguat, therefore, has potential as a novel therapy for PAH and CTEPH. This review is focused on various aspects of the recently approved "riociguat" including its efficacy and safety profiles with the clinical data highlighting its importance in the present scenario.

  10. Compound BMPR2 gene mutations in a malignant variant of idiopathic pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Walter Serra

    2014-12-01

    Full Text Available Pulmonary arterial hypertension (PAH; MIM 600799 is frequently associated with concomitant diseases, including congenital heart disease. 6% of patients with PAH show a family history of the disease [hereditary PAH (HPAH], with the major genetic determinants of HPAH being heterozygous germline mutations in the bone morphogenetic protein type II receptor (BMPR2. We present the case of a 38-year-old woman of Indian descent; initially admitted with progressive dyspnea [New York Heart Association (NYHA class III]. The results of the proband’s clinical assessments are presented here. Cardiac catheterization confirmed idiopathic PAH with severe right ventricular hypertrophy associated with pulmonary arteriopathy. Initial treatment comprised the dual endothelin receptor antagonist, bosentan, furosemide, warfarin and intravenous infusion of prostaglandin I2 (PGI2 for 3 days. Despite this, the patient died of pulmonary hemorrhagic edema and cardiogenic shock after 6 days of intensive care. After relatives’ consent, post mortem assessments confirmed a diagnosis of PAH; the heart displayed significant right ventricular hypertrophy and it was particularly noted that the right atrial appendage had undergone extreme dilation. Pulmonary arteriopathy was characterized by medial hypertrophy, arterialization of muscular arteries and muscularization of non-muscularized distal arteries. Molecular genetic analyses revealed the presence of cis-mutations in the BMPR2 gene (p.Cys123Arg and p.Arg332X. Cosegregation studies were not available. Our findings suggest that mutations of the BMPR2 gene gave rise to the onset of PAH in this patient and that the severity of the onset and progression could be attributed to the presence of multiple mutations in a genedosage manner.

  11. "Nocturnal seizures" in idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V

    2013-10-15

    The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children.

  12. Relation between arterial hypertension and hearing loss

    Directory of Open Access Journals (Sweden)

    Mondelli, Maria Fernanda Capoani Garcia

    2009-03-01

    Full Text Available Objective: To verify the relationship between systemic arterial hypertension (SAH and hearing loss in middle-aged patient. Method: This study was carried out in the period from January to December 2007. The research was composed by 392 patients of both genders, aged from 45 to 60 years old. Anamnesis and threshold tonal audiometry data were analyzed. Results: There was a significant association between SAH and hearing loss. Conclusion: The results showed an evident association between SAH and hearing loss, which requires the disclosure of a preventive process.

  13. Interleukin-6 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Yoshiaki Furuya

    2010-01-01

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine with a wide range of biologic activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Recent accumulating evidence indicates a pathologic role for IL-6 in promoting proliferation of both smooth muscle and endothelial cells in the pulmonary arterioles, resulting in development of pulmonary arterial hypertension (PAH. Here, we describe a patient with mixed connective tissue disease and severe, refractory PAH. Her functional activity and hemodynamic parameters dramatically responded to tocilizumab, a humanized monoclonal antibody to human IL-6 receptor, which was aimed at treating multicentric Castleman's disease. It appears that IL-6 blockade may hold promise as an adjunct drug in treatment of PAH in idiopathic form as well as in association with connective tissue disease.

  14. Survival in an incident cohort of patients with pulmonary arterial hypertension in Denmark

    DEFF Research Database (Denmark)

    Korsholm, Kasper Krohn; Andersen, Asger; Kirkfeldt, Rikke E

    2015-01-01

    We aimed to characterize and estimate survival rates in patients diagnosed with pulmonary arterial hypertension (PAH) in western Denmark in the modern management era. All incident cases of PAH were consecutively enrolled in our single-center prospective cohort study between January 2000 and March...... 2012. A total of 134 patients fulfilling the inclusion criteria were followed up from first diagnostic right heart catheterization to either death or the end of the study. Kaplan-Meier survival analysis was used to estimate 1-, 3-, and 5-year survival rates with 95% confidence intervals (CIs). Survival...... in the total cohort was 86.4% (95% CI, 79.3%-91.2%) after 1 year, 72.9% (95% CI, 64.1%-79.9%) after 3 years, and 65.4% (95% CI, 55.8%-73.4%) after 5 years. Significantly better survival was seen in the group of patients with PAH associated with congenital heart disease than in the group of patients...

  15. Safety and tolerability considerations in the use of sildenafil for children with pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Dodgen AL

    2015-12-01

    Full Text Available Andrew L Dodgen,1 Kevin D Hill1,2 1Department of Pediatrics, Duke University Medical Center, 2Duke Clinical Research Institute, Durham, NC, USA Abstract: Sildenafil is a phosphodiesterase type-5 inhibitor approved for treatment of pulmonary arterial hypertension (PAH in adults. Data from pediatric trials demonstrate a similar acute safety profile to the adult population but have raised concerns regarding the safety of long-term use in children. Interpretation of these trials remains controversial with major regulatory agencies differing in their recommendations – the US Food and Drug Administration recommends against the use of sildenafil for treatment of PAH in children, while the European Medicines Agency supports its use at “low doses”. Here, we review the available pediatric data regarding dosing, acute, and long-term safety and efficacy of sildenafil for the treatment of PAH in children. Keywords: phosphodiesterase inhibitor, pulmonary vasodilator, STARTS trials

  16. Safety and tolerability considerations in the use of sildenafil for children with pulmonary arterial hypertension

    Science.gov (United States)

    Dodgen, Andrew L; Hill, Kevin D

    2015-01-01

    Sildenafil is a phosphodiesterase type-5 inhibitor approved for treatment of pulmonary arterial hypertension (PAH) in adults. Data from pediatric trials demonstrate a similar acute safety profile to the adult population but have raised concerns regarding the safety of long-term use in children. Interpretation of these trials remains controversial with major regulatory agencies differing in their recommendations – the US Food and Drug Administration recommends against the use of sildenafil for treatment of PAH in children, while the European Medicines Agency supports its use at “low doses”. Here, we review the available pediatric data regarding dosing, acute, and long-term safety and efficacy of sildenafil for the treatment of PAH in children. PMID:26719728

  17. Safety and tolerability considerations in the use of sildenafil for children with pulmonary arterial hypertension.

    Science.gov (United States)

    Dodgen, Andrew L; Hill, Kevin D

    2015-01-01

    Sildenafil is a phosphodiesterase type-5 inhibitor approved for treatment of pulmonary arterial hypertension (PAH) in adults. Data from pediatric trials demonstrate a similar acute safety profile to the adult population but have raised concerns regarding the safety of long-term use in children. Interpretation of these trials remains controversial with major regulatory agencies differing in their recommendations - the US Food and Drug Administration recommends against the use of sildenafil for treatment of PAH in children, while the European Medicines Agency supports its use at "low doses". Here, we review the available pediatric data regarding dosing, acute, and long-term safety and efficacy of sildenafil for the treatment of PAH in children.

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

    Science.gov (United States)

    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.

  19. Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in Experimental Pulmonary Artery Hypertension.

    Science.gov (United States)

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

    2015-11-01

    Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter (AFL), is common in patients with pulmonary arterial hypertension (PAH), who often have increased sympathetic nerve activity. Here, we tested the hypothesis that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The atrial effective refractory period and AF/AFL inducibility at baseline and after anterior right ganglionated plexi ablation were determined during left stellate ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs with or without PAH. Then, sympathetic nerve, β-adrenergic receptor densities and connexin 43 expression in atrial tissues were assessed. The sum of the window of vulnerability to AF/AFL was increased in the right atrium compared with the left atrium at baseline in the PAH dogs but not in the controls. The atrial effective refractory period dispersion was increased in the control dogs, but not in the PAH dogs, during left stellate ganglion stimulation. The voltage thresholds for inducing AF/AFL during anterior right ganglionated plexi stimulation were lower in the PAH dogs than in the controls. The AF/AFL inducibility was suppressed after ablation of the anterior right ganglionated plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and β1-adrenergic receptor densities, increased levels of nonphosphorylated connexin 43, and heterogeneous connexin 43 expression in the right atrium when compared with the control dogs. The anterior right ganglionated plexi play important roles in the induction of AF/AFL. AF/AFL induction was associated with right atrium substrate remodeling in dogs with PAH.

  20. Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery.

    Science.gov (United States)

    Vaidya, Bhuvaneshwar; Gupta, Vivek

    2015-08-10

    Pulmonary arterial hypertension (PAH) is a cardiopulmonary disorder characterized by increased blood pressure in the small arterioles supplying blood to lungs for oxygenation. Advances in understanding of molecular and cellular biology techniques have led to the findings that PAH is indeed a cascade of diseases exploiting multi-faceted complex pathophysiology, with cellular proliferation and vascular remodeling being the key pathogenic events along with several cellular pathways involved. While current therapies for PAH do provide for amelioration of disease symptoms and acute survival benefits, their full therapeutic potential is hindered by patient incompliance and off-target side effects. To overcome the issues related with current therapy and to devise a more selective therapy, various novel pathways are being investigated for PAH treatment. In addition, inability to deliver anti-PAH drugs to the disease site i.e., distal pulmonary arterioles has been one of the major challenges in achieving improved patient outcomes and improved therapeutic efficacy. Several novel carriers have been explored to increase the selectivity of currently approved anti-PAH drugs and to act as suitable carriers for the delivery of investigational drugs. In the present review, we have discussed potential of various novel molecular pathways/targets including RhoA/Rho kinase, tyrosine kinase, endothelial progenitor cells, vasoactive intestinal peptide, and miRNA in PAH therapeutics. We have also discussed various techniques for site-specific drug delivery of anti-PAH therapeutics so as to improve the efficacy of approved and investigational drugs. This review will provide gainful insights into current advances in PAH therapeutics with an emphasis on site-specific drug payload delivery.

  1. Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.

    Science.gov (United States)

    Umar, Soban; Nadadur, Rangarajan D; Li, Jingyuan; Maltese, Federica; Partownavid, Parisa; van der Laarse, Arnoud; Eghbali, Mansoureh

    2011-09-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid (ILP), a source of parenteral nutrition for patients, contains γ-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We, therefore, investigated the therapeutic potential of ILP in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (60 mg/kg). Rats then received daily ILP (1 mL of 20% ILP per day IP) from day 1 to day 30 for prevention protocol or from day 21 to day 30 for rescue protocol. Other monocrotaline-injected rats were left untreated to develop severe PAH by day 21 or RV failure by approximately day 30. Saline or ILP-treated rats served as controls. Significant increase in RV pressure and decrease in RV ejection fraction in the RV failure group resulted in high mortality. Therapy with ILP resulted in 100% survival and prevented PAH-induced RV failure by preserving RV pressure and RV ejection fraction and preventing RV hypertrophy and lung remodeling. In preexisting severe PAH, ILP attenuated most lung and RV abnormalities. The beneficial effects of ILP in PAH seem to result from the interplay of various factors, among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy, in both lung and RV, appear to be major contributors. In conclusion, ILP not only prevents the development of PAH and RV failure but also rescues preexisting severe PAH.

  2. Risk factors associated with pulmonary arterial hypertension in patients with systemic sclerosis and implications for screening

    Directory of Open Access Journals (Sweden)

    C.P. Denton

    2011-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a relatively common complication of systemic sclerosis (SSc affecting 5–12% of patients, and its development is associated with significant morbidity and a particularly poor prognosis. Deaths associated with other complications of SSc, such as renal crisis, have fallen significantly in recent years in line with improvements in their treatment and management. However, mortality due to PAH in this population, although improved, has shown a less dramatic decline. The early diagnosis of PAH in SSc would allow for earlier treatment, before functional and haemodynamic impairment becomes severe; this may further improve outcome, and evidence suggests that screening of SSc patients for PAH is associated with improved survival. In addition, patients with PAH associated with SSc are not a homogeneous population and they differ in terms of disease haemodynamic severity, functional capacity and rate of disease progression. Likewise, management strategies may differ, and the ability to stratify patients may help optimise screening and treatment. A number of patient-, clinical- and disease-specific risk factors associated with the development and prognosis of PAH in SSc have been identified, but their optimal use, alone or in combination, in screening and stratification of patients remains to be established.

  3. Role for Functional SOD2 Polymorphism in Pulmonary Arterial Hypertension in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Ming Xu

    2017-03-01

    Full Text Available The superoxide dismutase 2 (SOD2 gene is a pivotal part of oxidative stress system, which could induce the onset of pulmonary arterial hypertension (PAH. In this study, we quantified the influence of a SOD2exonic polymorphism (rs4880 on PAH susceptibility. We genotyped this single nucleotide polymorphism (SNP by TaqMan, and evaluated its association with PAH susceptibility in a case-control study of 460 patients and 530 controls in China. There were significant differences between PAH cases and controls in both CC and TC+CC genotypes (p = 0.013 and p = 0.010, respectively. Furthermore, the number of variant alleles followed a dose-response manner (p trend was 0.023. Besides, the mRNA level and protein expression also indicated that the C allele of this variant decreased the expression of SOD2 gene (p = 0.004 in mRNA level and p = 0.012 in protein level after the transfection of plasmids containing the different genotype of rs4480. There is significant association between SOD rs4880 polymorphism and the PAH susceptibility, and this polymorphism influenced PAH susceptibility by altering the expression of SOD2.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. [Arterial hypertension in females engaged into penal system work].

    Science.gov (United States)

    Tagirova, M M; El'garov, A A; Shogenova, A B; Murtazov, A M

    2010-01-01

    The authors proved significant prevalence of arterial hypertension and atherosclerosis risk factors in women engaged into penal system work--so these values form cardiovascular risk caused by environmental parameters. Teveten and Nebilet were proved effective in the examinees with arterial hypertension.

  6. 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.)

  7. Apelin and pulmonary hypertension

    DEFF Research Database (Denmark)

    Andersen, Charlotte Uggerhøj; Hilberg, Ole; Mellemkjær, Søren;

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin...... vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting...

  8. The structural factor of hypertension: large and small artery alterations.

    Science.gov (United States)

    Laurent, Stéphane; Boutouyrie, Pierre

    2015-03-13

    Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.

  9. Treatment of idiopathic/hereditary pulmonary arterial hypertension.

    Science.gov (United States)

    Matsubara, Hiromi; Ogawa, Aiko

    2014-10-01

    Treatment of pulmonary hypertension has progressed by recently developed pulmonary arterial hypertension-targeted drugs. However, long-term survival of the patients with idiopathic/heritable pulmonary arterial hypertension is still suboptimal. To improve the outcomes, treatment goals of pulmonary hypertension were proposed at the 5th World Symposium on Pulmonary Hypertension held at Nice, France in 2013; parameters were obtained from cardiopulmonary exercise test, blood tests, echocardiography, and magnetic resonance imaging. In particular, parameters evaluating right ventricular function have been highlighted because survival of the patients with pulmonary arterial hypertension is closely related to right ventricular function. However, treatment specifically targeted to improve right ventricular function in pulmonary hypertension is not yet established. In this setting, we need to maintain or improve right ventricular function with available vasodilators. In this review, we focus on the following two points: (1) Why can pulmonary arterial hypertension-targeted drugs improve right ventricular function without an apparent decrease in pulmonary artery pressure? (2) Are proposed goals sufficient to improve long-term prognosis of the patients? Further, we will discuss what would be the appropriate goal in treating patients with pulmonary arterial hypertension.

  10. A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy

    OpenAIRE

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-01-01

    Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertensi...

  11. Arterial hypertension in chronic glomerulonephritis. An analysis of 310 cases.

    Science.gov (United States)

    Danielsen, H; Kornerup, H J; Olsen, S; Posborg, V

    1983-06-01

    310 cases of glomerulonephritis classified morphologically according to the criteria of the WHO were analyzed retrospectively in order to determine the frequency of arterial hypertension. The overall prevalence of arterial hypertension was 61%. Hypertension was most frequent and severe in membranoproliferative and sclerotic glomerulonephritis, but often mild and transient in extracapillary glomerulonephritis. Hypertension usually developed during the early stages of the disease when kidney function was well preserved and in only 16% was hypertension first seen during the uremic stage. No correlation was found between hypertension and the presence of the nephrotic syndrome. During dialysis, hypertension was present in 78%; in 90% of these patients hypertension was "controllable" and in 10% it was "uncontrollable".

  12. Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Saigal, Aparna; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

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

    Science.gov (United States)

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

    2016-10-01

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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    M. Rizzo

    2011-09-01

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

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

    Science.gov (United States)

    Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi

    2012-01-01

    Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.

  17. Renin and aldosterone measurements in the management of arterial hypertension.

    Science.gov (United States)

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy.

  18. The assessment of breathlessness in pulmonary arterial hypertension: reliability and validity of the Dyspnoea-12.

    Science.gov (United States)

    Yorke, Janelle; Armstrong, Iain

    2014-12-01

    Breathlessness is a cardinal symptom of pulmonary arterial hypertension (PAH); yet no breathlessness instrument has been previously tested for reliability and validity for this population. Using a cross-sectional design, we tested the psychometric properties of the Dyspnoea-12 (D-12), for the assessment of breathlessness in PAH. Pearson's correlations with World Health Organization functional class (WHO FC), Minnesota Living with Heart failure - pulmonary hypertension modified version (MLHF-PH), Hospital Anxiety and Depression scale (HADS) and 6-minute walk distance test (6MWD) were conducted. Participants (n = 176) were mostly female (70.5%), mean age 54.3±14 years; diagnosed with idiopathic PAH (48.9%), congenital heart disease (27.8%) and connective tissue disease (23.3%); and most were WHO FC II (32.4%) and III (52.3%). The D-12 showed excellent internal consistency for the total and two-component scores for physical and emotional (Cronbach's α 0.95, 0.93 and 0.94, respectively). D-12 total score was significantly associated with MLHF-PH (r = 0.70), HADS (anxiety r = 0.54 and depression r = 0.68), WHO FC (r = 0.49), and 6MWD (r = -0.26). In patients with PAH, the D-12 - a short patient reported measure of breathlessness severity that taps the physical and emotional components, is a reliable and valid instrument.

  19. 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

    were 130 normotensive cirrhotic patients, 19 controls with normal arterial blood pressure and without liver disease, and 16 patients with essential arterial hypertension. All groups underwent haemodynamic investigation with determination of cardiac output (CO), plasma volume (PV), central blood volume...

  20. Clinical utility of treprostinil in the treatment of pulmonary arterial hypertension: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Buckley MS

    2014-06-01

    Full Text Available Mitchell S Buckley,1 Andrew J Berry,1 Nadine H Kazem,2 Shardool A Patel,3 Paul A Librodo41Department of Pharmacy, Banner Good Samaritan Medical Center, Phoenix, AZ, USA; 2Department of Pharmacy, St Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; 3Department of Pharmacy, Banner Estrella Medical Center, Phoenix, AZ, USA; 4Department of Pharmacy, San Francisco VA Medical Center, San Francisco, CA, USAAbstract: Pulmonary arterial hypertension (PAH remains a progressive disease without a cure, despite the development of several treatment options over the past several decades. Its management strategy consists of the endothelin receptor antagonists (ambrisentan, bosentan, macitentan, phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil, and prostacyclin analogs (epoprostenol, treprostinil, iloprost. Treprostinil, a stable prostacyclin analog, displays vasodilatory effects in the pulmonary vasculature, as well as antiplatelet aggregation properties. Clinical practice guidelines recommend oral endothelin receptor antagonist or phosphodiesterase inhibitor therapy in mild to moderate PAH. Epoprostenol is specifically suggested as first-line therapy in moderate to severe PAH patients (ie, World Health Organization/New York Heart Association functional class III–IV. However, treprostinil may be an alternative option in these severe PAH patients. The longer half-life and stability at room temperature with treprostinil may be associated with lower risk of pulmonary hemodynamic worsening as a result of abrupt infusion discontinuation and less frequent drug preparation. These characteristics make treprostinil an attractive alternative to continuous infusion of epoprostenol, due to convenience and patient safety. The purpose of this review is to evaluate the safety and efficacy of continuous infusion of treprostinil as well as the inhaled and oral routes of administration in PAH.Keywords: treprostinil, prostacyclin, pulmonary arterial

  1. In situ expression of Bcl-2 in pulmonary artery endothelial cells associates with pulmonary arterial hypertension relative to heart failure with preserved ejection fraction

    Science.gov (United States)

    Benza, Raymond L.; Williams, Gretchen; Wu, Changgong; Shields, Kelly J.; Raina, Amresh; Murali, Srinivas

    2016-01-01

    Abstract We have previously reported that pulmonary artery endothelial cells (PAECs) can be harvested from the tips of discarded Swan-Ganz catheters after right heart catheterization (RHC). In this study, we tested the hypothesis that the existence of an antiapoptotic phenotype in PAECs obtained during RHC is a distinctive feature of pulmonary arterial hypertension (PAH; World Health Organization group 1) and might be used to differentiate PAH from other etiologies of pulmonary hypertension. Specifically, we developed a flow cytometry-based measure of Bcl-2 activity, referred to as the normalized endothelial Bcl-2 index (NEBI). We report that higher NEBI values are associated with PAH to the exclusion of heart failure with preserved ejection fraction (HFpEF) and that this simple diagnostic measurement is capable of differentiating PAH from HFpEF without presenting addition risk to the patient. If validated in a larger, multicenter study, the NEBI has the potential to assist physicians in the selection of appropriate therapeutic interventions in the common and dangerous scenario wherein patients present a clinical and hemodynamic phenotype that makes it difficult to confidently differentiate between PAH and HFpEF. PMID:28090298

  2. Exhaled and arterial levels of endothelin-1 are increased and correlate with pulmonary systolic pressure in COPD with pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Dragonieri Silvano

    2008-09-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 and Nitric Oxide (NO are crucial mediators for establishing pulmonary artery hypertension (PAH. We tested the hypothesis that their imbalance might also occur in COPD patients with PAH. Methods The aims of the study were to measure exhaled breath condensate (EBC and circulating levels of ET-1, as well as exhaled NO (FENO levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12, COPD only (36, and healthy individuals (15. In order to evaluate pulmonary-artery systolic pressure (PaPs, all COPD patients underwent Echo-Doppler assessment. Results Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p 1%, (r = -0.59, p = 0.043, and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032. Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 ± 11.38 vs.35.07 ± 17.53 ppb; p = 0.03. Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations.

  3. 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.

  4. Exhaled nitric oxide in pulmonary arterial hypertension associated with systemic sclerosis

    Science.gov (United States)

    Mathai, Stephen C.; Hummers, Laura K.; Shah, Ami A.; Wigley, Fredrick M.; Lechtzin, Noah; Hassoun, Paul M.; Girgis, Reda E.

    2016-01-01

    Abstract The fractional exhaled concentration of nitric oxide (FENO) has been shown to be reduced in idiopathic pulmonary arterial hypertension (PAH) but has not been adequately studied in PAH associated with systemic sclerosis (SSc). We measured FENO at an expiratory flow rate of 50 mL/s in 21 treatment-naive patients with SSc-associated PAH (SSc-PAH), 94 subjects with SSc without pulmonary involvement, and 84 healthy volunteers. Measurements of FENO at additional flow rates of 100, 150, and 250 mL/s were obtained to derive the flow-independent nitric oxide exchange parameters of maximal airway flux (J′awNO) and steady-state alveolar concentration (CANO). FENO at 50 mL/s was similar (P = 0.22) in the SSc-PAH group (19 ± 12 parts per billion [ppb]) compared with the SSc group (17 ± 12 ppb) and healthy control group (21 ± 11 ppb). No change was observed after 4 months of targeted PAH therapy in 14 SSc-PAH group patients (P = 0.9). J′awNO was modestly reduced in SSc group subjects without lung disease (1.2 ± 0.5 nl/s) compared with healthy controls (1.64 ± 0.9; P < 0.05) but was similar to that in the SSc-PAH group. CANO was elevated in individuals with SSc-PAH (4.8 ± 2.6 ppb) compared with controls with SSc (3.3 ± 1.4 ppb) and healthy subjects (2.6 ± 1.5 ppb; P < 0.001 for both). However, after adjustment for the diffusing capacity of CO, there was no significant difference in CANO between individuals with SSc-PAH and controls with SSc. We conclude that FENO is not useful for the diagnosis of PAH in SSc. Increased alveolar nitric oxide in SSc-PAH likely represents impaired diffusion into pulmonary capillary blood. PMID:28090297

  5. Computational modeling of hypertensive growth in the human carotid artery

    Science.gov (United States)

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-06-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.

  6. Quercetin reverses experimental pulmonary arterial hypertension by modulating the TrkA pathway.

    Science.gov (United States)

    He, Yuanzhou; Cao, Xiaopei; Liu, Xiansheng; Li, Xiaochen; Xu, Yongjian; Liu, Jin; Shi, Jing

    2015-11-15

    Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation, resistance to apoptosis, and increased migration of pulmonary artery smooth muscle cells (PASMCs). We hypothesized that quercetin exerts protective effects against this disease; thus, a chronic hypoxia model of PAH was generated using male Sprague-Dawley rats, which were treated with quercetin. In this model, quercetin prevented the development of PAH, right ventricular hypertrophy, and vascular remodeling after exposure to hypoxia. Quercetin inhibited PASMC proliferation and increased the apoptosis of PASMCs in vivo. In vitro, quercetin significantly inhibited hypoxia-induced PASMC proliferation, arrested cells in G1/G0 and inhibited cell migration in a dose-dependent manner. Moreover, our results showed that quercetin increased cyclin D1 protein levels and decreased the protein expression of cyclin B1 and Cdc2. Additionally, quercetin altered the Bax/Bcl-2 ratio and reduced MMP2, MMP9, CXCR4, integrin β1, and integrin α5 expression. Using genome-wide microarray analysis, we found that factors regulating proliferation, apoptosis, cell cycle, and migration were related to the tyrosine receptor kinase A (TrkA) pathway. In addition, activation of the TrkA/AKT signaling cascade during hypoxia was inhibited by quercetin in a dose-dependent manner. Moreover, quercetin alone inhibited the TrkA/AKT signaling pathway, resulting in decreased PASMC migration, cell cycle arrest and the induction of apoptosis. Our data suggest that quercetin is a potential candidate for the treatment of hypoxia-induced PAH.

  7. Left Ventricular Diastolic Function Assessment of a Heterogeneous Cohort of Pulmonary Arterial Hypertension Patients

    Science.gov (United States)

    Hernandez-Suarez, Dagmar F.; Lopez Menendez, Francisco R.; Palm, Denada; Lopez-Candales, Angel

    2017-01-01

    Background Pulmonary arterial hypertension (PAH) is known to trigger right ventricular (RV) remodeling that might compromise left ventricular (LV) filling due to inter-ventricular interdependence. In this study, we aimed to examine standard echocardiographic measurements of LV diastolic function in PAH patients. Methods In this retrospective study, we identified clinical as well as complete echocardiographic data from 128 chronic PAH patients to fully assess LV diastolic dysfunction (LVDD) using standard recommended Doppler guidelines. Accordingly, patients were divided into three groups: LVDD 0, LVDD 1 and LVDD 2. Results The mean age of the studied population was 57 ± 14 years with a mean pulmonary artery systolic pressure (PASP) of 55 ± 21 mm Hg. A total of 36% of the study patients had normal LV diastolic function. However, 64% had LVDD with LVDD stage 1 being the most common (48%). In terms of echocardiographic data, significant differences were found among the three LVDD groups in regards to PASP, LV end systolic and diastolic volumes, tricuspid annular plane systolic excursion, right ventricular fractional area change as well as many other tissue Doppler imaging parameters. Finally, just age and PASP were predictors of abnormal LV diastolic function (P < 0.05). Conclusions Impaired relaxation is a common abnormality in PAH patients. Additional studies are warranted to determine whether LVDD alters prognosis or is related to changes in the symptomatic profile of this group of patients. PMID:28270896

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian [German Cancer Research Center DKFZ, Department of Radiology (E010), Heidelberg (Germany); University Heidelberg, Department of Pediatric Radiology, Heidelberg (Germany); Mereles, Derliz; Gruenig, Ekkehard [University Heidelberg, Department of Internal Medicine III, Heidelberg (Germany); Puderbach, Michael; Schoeck, Helena; Eichinger, Monika; Ley-Zaporozhan, Julia; Fink, Christian; Kauczor, Hans-Ulrich [German Cancer Research Center DKFZ, Department of Radiology (E010), Heidelberg (Germany)

    2007-07-15

    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{sup 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.)

  10. Prognostic markers for idiopathic pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Guo Xiaomin; Jin Hongfang; Du Junbao

    2014-01-01

    Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension (IPAH).Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.

  11. A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy.

    Science.gov (United States)

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-12-06

    Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.

  12. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    Science.gov (United States)

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

  13. Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Abdul Q. Sheikh

    2014-03-01

    Full Text Available Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.

  14. Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

    Science.gov (United States)

    2013-01-01

    Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Results Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. Conclusions The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion. PMID:23339456

  15. [FEATURES OF ARTERIAL HYPERTENSION IN THE WORKING POPULATION].

    Science.gov (United States)

    Mershenova, G; Kossybayeva, M; Chancharov, B; Mirzayeva, B; Amangeldiyeva, K

    2017-01-01

    Purpose of the research was to study clinical features of arterial hypertension in the working population in Karaganda. The number of participants (500 patients): base group (250 patients) and control group (250 patients). The criteria for inclusion (age and gender characteristics, diseases/conditions and etc): age from 18 to 63 years; presence of arterial hypertension 1, 2 and 3 grades; possibility to measure the arterial pressure in dynamic; patients, who agreed to participate in the research work (the existence of informed consent). The criteria for an exception: children under 18 years, pregnant, the patient's refusal to participate in the research work. Methods of research - retrospective analysis of patients card in base and control groups at the working population of the city of Karaganda; physical examinations (anthropometrical indicators) in base and control groups. The processing and analysis of materials was conducted by using the average values and their standard errors. Significance of differences of independent sets of were estimated with parametric and nonparametric methods. In the study group compared with control were more common all the risk factors of hypertension, especially hypercholesterolemia and dyslipidemia in half of the cases in patients with arterial hypertension working age. We believe that the main factors of risk in arterial hypertension are hypercholesterolemia and dyslipidemia with combination in other factors, affecting mainly on the course and outcome of hypertension. Degrees of hypertension was dependent from age of patients and duration of illness, there was a trend more pronounced degree of hypertension in men than in women. In men with slavic nationality was more pronounced hypertension 1,2 and 3 degree, while in Kazakh nationality men often was observed hypertension 1, 2 degree. The degree of hypertension in the study group depending on the mental and physical labor did not observed. Hypertension 2-3 degrees was observed at

  16. A CASE OF IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION IN MALE

    Directory of Open Access Journals (Sweden)

    Poongavanam Paranthaman

    2016-08-01

    Full Text Available 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 case of middle-aged male who presented with dyspnoea and on further evaluation found to have primary pulmonary hypertension, which is uncommon in male

  17. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension

    OpenAIRE

    Doran, A. K.; Ivy, D. D.; Barst, R.J.; Hill, N.; Murali, S; Benza, R. L.

    2008-01-01

    Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life. Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin). Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care ...

  18. Adult patients with pulmonary arterial hypertension due to congenital heart disease: a review on advanced medical treatment with bosentan

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    Mark J Schuuring

    2010-08-01

    Full Text Available Mark J Schuuring1,2, Jeroen C Vis1,2, Marielle G Duffels1, Berto J Bouma1, Barbara JM Mulder1,21Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands; 2Interuniversity Cardiology Institute of The Netherlands, Utrecht, The NetherlandsAbstract: Pulmonary arterial hypertension (PAH is a progressive disease with poor survival outcome. PAH is classified by the 2009 updated clinical classification of pulmonary hypertension and a major subgroup is PAH due to congenital heart disease (CHD with systemic-to-pulmonary shunt. CHD-PAH is a result of systemic-to-pulmonary shunting and chronic increased flow that ultimately results in adaptations of pulmonary vasculature and endothelial dysfunction. The advanced stage is called Eisenmenger syndrome which forms a small percentage (1% of all CHD patients. Therapies targeted on PAH symptoms are called primary therapy for PAH, but most CHD-PAH patients progress to advanced therapy which is directed at the PAH itself. In CHD-PAH, advanced therapies are extensively investigated for all three major pathways: endothelin-1 receptor antagonists such as bosentan, prostanoids such as epoprostenol and phosphodiesterase 5 inhibitors such as sildenafil. Endpoints in most trials were catheterization hemodynamics, World Health Organization functional class, six-minute walking distance and patient-focused outcomes, based on quality of life questionnaires and Borg dyspnea index. The BREATHE-5 and EARLY study were two important randomized controlled trials showing efficacy of bosentan at short follow-up. Moreover in patients with Eisenmenger syndrome, one recent survival retrospective study with majority of patients on bosentan showed strong survival benefit over conservative therapy. A diversity of prospective cohort and retrospective studies were performed but all with limited data, due to small numbers and heterogeneity of underlying CHD diagnoses. Further larger studies are needed to determine optimal

  19. Progress in anti-endothelin therapy in the treatment of pulmonary arterial hypertension and heart failure

    Institute of Scientific and Technical Information of China (English)

    MAYANJA Patrick; MA Gen-shan

    2014-01-01

    Endothelin-1 ( ET-1 ) is not only a potent vasoconstrictor , but causes proliferation of many of the vascular cells involved in vascular remodelling .ETA receptors mediate vasoconstriction and cell proliferation , whereas ETB receptors are important for the clearance of ET-1, endothelial cell survival , the release of nitric oxide and prostacyclin , and the inhibition of endothelin-converting enzyme ( ECE )-1.ET is activated in pulmonary arterial hypertension ( PAH) , heart failure ( HF) and many other cardiovascular diseases .The most efficient way to antagonize the ET-1 system is the use of ET-1 receptor antagonists that can block either ETA-or ETA-and ETB-receptors, or ECE inhibition which blocks the conversion of big ET-1 to ET-1.In this brief review , we will try to summarize the progress of anti-endothelin therapy in the treatment of PAH and HF treatment therapies .

  20. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

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    Mehdi Peighambari

    2012-09-01

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

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

    Science.gov (United States)

    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.

  2. Arterial pulmonary hypertension in noncardiac intensive care unit

    Directory of Open Access Journals (Sweden)

    Mykola V Tsapenko

    2008-10-01

    Full Text Available Mykola V Tsapenko1,5, Arseniy V Tsapenko2, Thomas BO Comfere3,5, Girish K Mour1,5, Sunil V Mankad4, Ognjen Gajic1,51Division of Pulmonary and Critical Care Medicine; 3Division of Critical Care Medicine; 4Division of Cardiovascular Diseases, Mayo Epidemiology and Translational Research in Intensive Care (M.E.T.R.I.C, Mayo Clinic, Rochester, MN, USA; 2Division of Pulmonary and Critical Care Medicine, Brown University, Miriam Hospital, Providence, RI, USAAbstract: Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in

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

    NARCIS (Netherlands)

    G.M. 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

  4. Quantitative Indexes of Leukocytes in Spontaneously Hypertensive Rats During Various Periods of Arterial Hypertension Development.

    Science.gov (United States)

    Aliev, O I; Anishchenko, A M; Sidekhmenova, A V; Shamanaev, A Yu; Fedorova, E P; Plotnikov, M B

    2015-10-01

    SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.

  5. 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.

  6. Effect of Th17 and Treg Axis Disorder on Outcomes of Pulmonary Arterial Hypertension in Connective Tissue Diseases

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    Saren Gaowa

    2014-01-01

    Full Text Available This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD, 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

  7. Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension.

    Science.gov (United States)

    West, James D; Austin, Eric D; Gaskill, Christa; Marriott, Shennea; Baskir, Rubin; Bilousova, Ganna; Jean, Jyh-Chang; Hemnes, Anna R; Menon, Swapna; Bloodworth, Nathaniel C; Fessel, Joshua P; Kropski, Johnathan A; Irwin, David; Ware, Lorraine B; Wheeler, Lisa; Hong, Charles C; Meyrick, Barbara; Loyd, James E; Bowman, Aaron B; Ess, Kevin C; Klemm, Dwight J; Young, Pampee P; Merryman, W David; Kotton, Darrell; Majka, Susan M

    2014-09-01

    Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis for disease. Previous studies on patient samples were limited by end-stage disease effects or by use of nonadherent cells, which are not ideal to model vascular cells in vivo. These studies addressed the hypothesis that pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments were initially conducted to analyze cell types at different stages of vascular differentiation (mesenchymal stromal and endothelial) derived from PAH patient-specific induced pluripotent stem (iPS) cells. Molecular pathways that were altered in the PAH cell lines were then compared with those in fibroblasts from 21 patients, including those with idiopathic and heritable PAH. Wnt was identified as a target pathway and was validated in vitro using primary patient mesenchymal and endothelial cells. Taken together, our data suggest that the molecular lesions that cause PAH are present in all cell types evaluated, regardless of origin, and that stimulation of the Wnt signaling pathway was a common molecular defect in both heritable and idiopathic PAH.

  8. Therapeutic approaches of uncomplicated arterial hypertension in patients with COPD.

    Science.gov (United States)

    Di Daniele, Nicola

    2015-12-01

    The concomitant presence of systemic arterial hypertension and chronic obstructive pulmonary disease (COPD) is frequent. Indeed, arterial hypertension is the most common comorbid disease in COPD patients. Since many antihypertensive drugs can act on airway function the treatment of arterial hypertension in COPD patients appears complex. Moreover, in these patients, a combined therapy is required for the adequate control of blood pressure. Currently, available data are inconsistent and not always comparable. Therefore the aim of this review is to analyze how antihypertensive drugs can affect airway function in order to improve the clinical management of hypertensive patients with COPD. Thiazide diuretics and calcium channel blockers appear the first-choice pharmacological treatment for these patients.

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

    Science.gov (United States)

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

    2016-07-01

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

  10. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

    Directory of Open Access Journals (Sweden)

    Tselios K

    2016-12-01

    Full Text Available Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, ON, Canada Abstract: Systemic lupus erythematosus (SLE is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH, after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg with normal pulmonary capillary wedge pressure (≤15 mmHg and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan, phosphodiesterase type 5 inhibitors (sildenafil, and vasodilators (epoprostenol. Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively. Keywords: systemic lupus erythematosus, pulmonary arterial hypertension, immunosuppressive, transthoracic echocardiogram, endothelin receptor antagonists

  11. Pulmonary Arterial Hypertension in Connective Tissue Diseases

    Directory of Open Access Journals (Sweden)

    Shunji Yoshida

    2011-01-01

    Most CTD-PH are PAH, and since idiopathic PAH (IPAH patients sometimes have immune disorders, treatment for IPAH may be applicable to CTD-PH. The greatest difference between the treatment strategy for CTD- PH and IPAH is the usage of corticosteroids and other immunosuppressants. The MCTD Research Committee updated its therapeutic guidelines for MCTD-PH in 2011. Validation of these guidelines is also needed.

  12. Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals

    Directory of Open Access Journals (Sweden)

    N. Galiè

    2010-12-01

    Full Text Available Major advances have occurred in the treatment of pulmonary arterial hypertension (PAH over the past decade. The advent of PAH-specific pharmacological treatments has offered hope to patients with a debilitating, progressive disease and a poor prognosis. Combined drug treatment offers improved benefits over monotherapy, and current treatment guidelines for PAH recommend a sequential add-on approach to combination therapy for patients in New York Heart Association (NYHA/World Health Organization functional class (WHO FC II–IV. Goal-oriented therapy determines the timing of treatment escalation by inadequate response to known prognostic indicators. Close monitoring of patients aids the early identification of inadequate response, so that treatment can be escalated promptly and before the patient's condition deteriorates further. Existing treatment goals are based on baseline values of prognostic indicators, but it is vital to identify risk factors that are both relevant during treatment and that can be assessed during follow-up appointments. Data from different PAH aetiologies indicate that NYHA/WHO FC is the most appropriate prognostic marker, with 6-min walk distance and several haemodynamic parameters representing alternatives. Future refinement of goal-oriented therapy could include the use of multiple prognostic markers, while additional, large clinical trials will answer questions concerning choice and combination of treatment goals.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

    Science.gov (United States)

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

    Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

  16. Diet and arterial hypertension: is the sodium ion alone important?

    Science.gov (United States)

    Buemi, Michele; Senatore, Massimino; Corica, Francesco; Aloisi, Carmela; Romeo, Adolfo; Tramontana, Domenico; Frisina, Nicola

    2002-07-01

    Hypertension is a widespread phenomenon whose ultimate cause is still unknown. Many factors contribute to this disease, and partially for this reason, hypertension responds to different treatments in different individuals. It is difficult to generalize about therapies for general populations. In particular, the role of electrolytes in hypertension varies widely across individuals. This review focuses its attention on sodium, potassium, calcium, and magnesium ions in order to investigate whether these electrolytes play a role in the pathogenesis of arterial hypertension and its treatment. Some individuals are especially sensitive to sodium, and changing their intake of dietary sodium may lead to variations in the levels of the other electrolytes. These changes in electrolyte levels can complicate treatments for arterial hypertension in some patients.

  17. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies.

    Science.gov (United States)

    Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B

    2017-01-01

    Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud's phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively.

  18. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

    Science.gov (United States)

    Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B

    2017-01-01

    Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively. PMID:28053559

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

    Directory of Open Access Journals (Sweden)

    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.

  20. The Contribution of Osteoprogenitor Cells to Arterial Stiffness and Hypertension.

    Science.gov (United States)

    Pikilidou, Maria; Yavropoulou, Maria; Antoniou, Maria; Yovos, John

    2015-01-01

    Hypertension, the major cause of cardiovascular disease, is bidirectionally linked to arterial stiffness. Evidence shows that vascular calcification, either medial or intimal, induces arterial stiffening further worsening hypertension parallel to substantially increasing cardiovascular risk. The disturbance in the bone-vascular axis that leads to the increase of calcium deposition in the arterial wall may be the result of a shift in the functionality of bone marrow-derived circulating stem cells with a calcifying potential, namely osteoprogenitor cells. These cells deposit bone matrix proteins in the vascular wall that can subsequently become mineralized. The current notion is that these cells derive from diverse cell lines. The present review summarizes the current knowledge on the role of progenitor cells with a calcifying potential on arterial calcification, stiffness and hypertension.

  1. Pulmonary arterial hypertension among HIV-infected children: results of a national survey and review of the literature

    Directory of Open Access Journals (Sweden)

    Arnaud Grégoire L'huillier

    2015-04-01

    Full Text Available Since the advent of highly active anti-retroviral therapy, HIV-related mortality has decreased dramatically. As a consequence, patients are living longer, and HIV infection is becoming a chronic disease. Patients and caretakers have to deal with chronic complications of infection and treatment, such as cardiovascular diseases, which now represent an important health issue, even in the pediatric population. Prevalence of pulmonary arterial hypertension (PAH in the adult HIV population is around 0.4-0.6%, which is around 1000 to 2500-fold more prevalent than in the general population. In recent adult PAH registries, HIV has been identified as the fourth cause of PAH, accounting for approximately 6-7% of cases. Therefore, regular screening is recommended in HIV-infected adults by many experts.If HIV-associated PAH is mainly reported in HIV-infected adults, pediatric cases have also been, albeit rarely, described. This scarcity may be due to a very low PAH prevalence, or due to the lack of systematic cardiovascular screening in pediatric patients. As PAH may manifest only years or decades after infection, a systematic screening should perhaps also be recommended to HIV-infected children. In this context, we retrospectively looked for PAH screening in children included in our national Swiss Mother and Child HIV (MoCHIV cohort study. A questionnaire was sent to all pediatric infectious disease specialists taking care of HIV-infected children in the cohort. The questions tried to identify symptoms suggestive of cardiovascular risk factors and asked which screening test was performed. In the 71 HIV-infected children for which we obtained an answer, no child was known for PAH. However, only two had been screened for PAH, and the diagnosis not confirmed.In conclusion, PAH in HIV-infected children is possibly underestimated due to lack of screening. Systematic echocardiographic evaluation should be performed in HIV-infected children.

  2. Pulmonary Arterial Hypertension among HIV-Infected Children: Results of a National Survey and Review of the Literature.

    Science.gov (United States)

    L'Huillier, Arnaud Grégoire; Posfay-Barbe, Klara Maria; Pictet, Hiba; Beghetti, Maurice

    2015-01-01

    Since the advent of highly active anti-retroviral therapy, HIV-related mortality has decreased dramatically. As a consequence, patients are living longer, and HIV infection is becoming a chronic disease. Patients and caretakers have to deal with chronic complications of infection and treatment, such as cardiovascular diseases, which now represent an important health issue, even in the pediatric population. Prevalence of pulmonary arterial hypertension (PAH) in the adult HIV population is around 0.4-0.6%, which is around 1000- to 2500-fold more prevalent than in the general population. In recent adult PAH registries, HIV has been identified as the fourth cause of PAH, accounting for approximately 6-7% of cases. Therefore, regular screening is recommended in HIV-infected adults by many experts. If HIV-associated PAH is mainly reported in HIV-infected adults, pediatric cases have also been, albeit rarely, described. This scarcity may be due to a very low PAH prevalence, or due to the lack of systematic cardiovascular screening in pediatric patients. As PAH may manifest only years or decades after infection, a systematic screening should perhaps also be recommended to HIV-infected children. In this context, we retrospectively looked for PAH screening in children included in our national Swiss Mother and Child HIV cohort study. A questionnaire was sent to all pediatric infectious disease specialists taking care of HIV-infected children in the cohort. The questions tried to identify symptoms suggestive of cardiovascular risk factors and asked which screening test was performed. In the 71 HIV-infected children for which we obtained an answer, no child was known for PAH. However, only two had been screened for PAH, and the diagnosis was not confirmed. In conclusion, PAH in HIV-infected children is possibly underestimated due to lack of screening. Systematic echocardiographic evaluation should be performed in HIV-infected children.

  3. The clinical characteristics of systemic sclerosis-related pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    王辉

    2014-01-01

    Objective To study the clinical,cardiopulmonary functional and hemodynamic profiles of systemic sclerosis patients with pulmonary hypertension(SSc-PAH)compared with those of idiopathic pulmonary hypertension(IPAH).Methods Patients diagnosed with SSc-PAH or IPAH by right heart catheterization were consecutively enrolled into the study between 2011 and 2013 in Peking

  4. [Treatment of arterial hypertension in children].

    Science.gov (United States)

    Bensman, A

    1988-01-01

    Hypertension in children is divided in 2 groups: primary hypertension and the secondary forms which are more severe and mostly due to kidney diseases. The medical management of hypertension includes non pharmacological intervention (diet, exercise, life-style) and pharmacological agents. The children with primary and mild hypertension may need only non pharmacological strategies. The main pharmacological agents used are: diuretics, vasodilators, sympathetic blockers, centrally acting agents, converting enzyme inhibitors. Except for hypertensive emergencies, the management of children with hypertension is facilitated by a stepped-care titration approach. Step 1: beta adrenergic blockers or vaso-dilators; step 2: combine beta adrenergic blockers with vaso-dilators or with diuretics or converting enzyme inhibitors alone; step 3: combine converting enzyme inhibitors with vaso-dilators and/or diuretics and/or beta adrenergic blockers; step 4: drugs include minoxidil, prazosin, labetalol.

  5. Structural abnormalities of small resistance arteries in essential hypertension.

    Science.gov (United States)

    Rizzoni, Damiano; Agabiti-Rosei, Enrico

    2012-06-01

    Regardless of the mechanisms that initiate the increase in blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, the small arteries smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, while in some secondary forms of hypertension, a hypertrophic remodeling may be detected. Also, in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling of subcutaneous small arteries is present. The results from our own group have suggested that indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Therefore, the regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure, both in human and in animal models of genetic and experimental hypertension. A complete normalization of small resistance artery structure is demonstrated in hypertensive patients, after long-term and effective therapy with ACE inhibitors, angiotensin II receptor blockers and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard. In conclusion, there are several pieces of evidence that suggest that small resistance artery structure may be considered an intermediate endpoint in the evaluation of the effects of antihypertensive therapy; however, there are presently no data available about the prognostic impact of the regression of vascular structural alterations in hypertension and diabetes.

  6. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    Science.gov (United States)

    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.

  7. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. (Univ. of Southern California School of Medicine, Los Angeles (USA))

    1990-06-01

    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.

  8. Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension

    Science.gov (United States)

    Kopeć, Grzegorz; Waligóra, Marcin; Tyrka, Anna; Jonas, Kamil; Pencina, Michael J.; Zdrojewski, Tomasz; Moertl, Deddo; Stokwiszewski, Jakub; Zagożdżon, Paweł; Podolec, Piotr

    2017-01-01

    Low-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26–0.74, p = 0.002) after a median follow-up time of 33(21–36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1–3.2] to 4.0[2.8–4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2–2.7] vs 2.3[2.1–2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels. PMID:28198422

  9. Differences of cardiac output measurements by open-circuit acetylene uptake in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a cohort study

    Directory of Open Access Journals (Sweden)

    Schwaiblmair Martin

    2012-03-01

    Full Text Available Abstract Background As differences in gas exchange between pulmonary arterial hypertension (PAH and chronic thromboembolic pulmonary hypertension (CTEPH have been demonstrated, we asked if cardiac output measurements determined by acetylene (C2H2 uptake significantly differed in these diseases when compared to the thermodilution technique. Method Single-breath open-circuit C2H2 uptake, thermodilution, and cardiopulmonary exercise testing were performed in 72 PAH and 32 CTEPH patients. Results In PAH patients the results for cardiac output obtained by the two methods showed an acceptable agreement with a mean difference of -0.16 L/min (95% CI -2.64 to 2.32 L/min. In contrast, the agreement was poorer in the CTEPH group with the difference being -0.56 L/min (95% CI -4.96 to 3.84 L/min. Functional dead space ventilation (44.5 ± 1.6 vs. 32.2 ± 1.4%, p 2 gradient (9.9 ± 0.8 vs. 4.1 ± 0.5 mmHg, p Conclusion Cardiac output evaluation by the C2H2 technique should be interpreted with caution in CTEPH, as ventilation to perfusion mismatching might be more relevant than in PAH.

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

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    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.

  11. The value of tools to assess pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    H. Gupta

    2011-12-01

    Full Text Available Pulmonary hypertension is a common but complex clinical problem. When suspected in an appropriate clinical setting or detected incidetally, an array of investigative tools are employed with an intent to confirm the diagnosis, define aetiology, evaluate the functional and haemodynamic impairment, define treatment options, monitor the therapy, and establish long-term prognosis. However, no single tool provides comprehensive information that encompasses the aforementioned aims. Therefore, judicious use of these tools is of paramount importance, in order to maximise outcome and cost-effectiveness, while minimising risks and redundancies. Furthermore, a number of promising tools and techniques are emerging rapidly in the arena of pulmonary hypertension. These tools augment our understanding of pathophysiology and natural history of pulmonary hypertension. There is, therefore, increasing need for validating these emerging paradigms in multicentre trials. In this review, we focus on the tools commonly used to evaluate pulmonary arterial hyertension and also define some of the new approaches to pulmonary arterial hypertension.

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

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    Rosa L.E. Loon

    2015-08-01

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

  13. Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Hadinnapola, Charaka; Pepke-Zaba, Joanna

    2015-10-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.

  14. Arterial hypertension in nursing personnel of an emergency hospital.

    Science.gov (United States)

    Urbanetto, Janete de Souza; Prado Lima Figueiredo, Ana Elizabeth; da Silva Gustavo, Andreia; Bosi de Souza Magnago, Tânia Solange; Pinheiro da Costa, Bartira Ercilia; Poli-de-Figueiredo, Carlos Eduardo

    2015-08-01

    Risk factors related to the workplace environment are being studied to identify positive associations with hypertension disorders. Hypertension is considered as one of the main modifiable risk factors and most important public health issues. The study aims to describe the prevalence of hypertension and associate it with sociodemographic, labour and health aspects, in the health-care nursing staff of an emergency hospital.Cross-sectional study enrolled 606 nursing workers. The data were collected from February to June, and the analysis was conducted in November 2010. Arterial blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) were assessed, and sociodemographic and labour variables were investigated by means of a questionnaire. The data were analysed by descriptive statistics, univariate and multivariate analysis. The prevalence of hypertension was 32% (n = 388), with positive associations with age > 49 years (OR = 2.55 (CI: 1.19 to 5.43)), ethnicity (non-white) (odds ratio (OR) = 2.22, confidence interval (CI) 1.16 to 1.24), BMI (OR = 2.24 (CI: 1.25 to 4.01)) and WHR (OR = 2.65 (CI: 1.95 to 7.763)). Arterial hypertension was frequent in the nursing staff of this emergency hospital. Further studies are needed to better understand the relationship between occupational aspects and arterial hypertension.

  15. Pulmonale arteriële hypertensie bij kinderen in Nederland

    NARCIS (Netherlands)

    Douwes, Johannes M; van Loon, Rosa L E; Roofthooft, Marcus T R; Berger, Rolf M F

    2011-01-01

    Progressive pulmonary arterial hypertension (PAH) is a rare condition with high morbidity and mortality. Paediatric PAH distinguishes itself from PAH in adults, but is still poorly characterized. Paediatric PAH presents itself with non-specific symptoms which often results in later diagnosis. Determ

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

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    Szema Anthony M

    2011-10-01

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

  17. Current insights on the pathogenesis of pulmonary arterial hypertension.

    Science.gov (United States)

    Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc

    2005-08-01

    Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.

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

    Science.gov (United States)

    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.

  19. Non-dipping status in arterial hypertension: an overview.

    Science.gov (United States)

    Sarigianni, Maria; Dimitrakopoulos, Konstantinos; Tsapas, Apostolos

    2014-05-01

    Non-dipping is a common pattern of arterial hypertension and it is associated with increased cardiovascular risk. Use of ambulatory blood pressure monitoring, as suggested in recent guidelines, could further increase its prevalence among subjects with hypertension. In this review we discuss assessment, relevance and associated factors. Non-dipping could be addressed through chronotherapy, the use of specific classes of anti-hypertensives, such as renin-angiotensin blockers, or modification of associated factors. However, more data are needed in order to comprehensively estimate factors associated with non-dipping and how they could be modified.

  20. How to manage hypertension with atherosclerotic renal artery stenosis?

    Science.gov (United States)

    Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

    2017-04-01

    The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

  1. Hypertension following Therapeutic Arterial Embolization: A Rare Complication

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    Ghansham Biyani

    2014-05-01

    Full Text Available Accelerated hypertension following therapeutic arterial embolization is a rare phenomenon. A patient of left upper limb chronic lymphedema was posted for shoulder disarticulation under general anaesthesia. Coil embolization of the left subclavian artery was done prior to surgery. Following the intervention, patient’s blood pressure increased by more than 30% of the base line value and was managed with antihypertensives for the next 3 hours to get the blood pressure optimised prior to taking the patient for surgery.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. A pathogenic role of complement in arterial hypertension and hypertensive end organ damage.

    Science.gov (United States)

    Wenzel, Ulrich O; Bode, Marlies; Köhl, Jörg; Ehmke, Heimo

    2017-03-01

    The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important roles in the regulation of adaptive immunity. Innate and adaptive immune responses have been identified as crucial players in the pathogenesis of arterial hypertension and hypertensive end organ damage. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.

  4. The use of combination therapy in pulmonary arterial hypertension: new developments

    Directory of Open Access Journals (Sweden)

    N. Galiè

    2009-09-01

    Full Text Available There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH, as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value.

  5. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course

    Science.gov (United States)

    Baldi, Fabiana; Fuso, Leonello; Arrighi, Eugenio; Valente, Salvatore

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers) have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. PMID:25328398

  6. Screening patients with scleroderma for pulmonary arterial hypertension and implications for other at-risk populations

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    Johannes P. Schwaiger

    2013-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a progressive vasculopathy that is advanced by the time symptoms develop. As symptoms are nonspecific and the condition uncommon, continued progression toward end-stage disease occurs for an average of 2 years between symptom onset and diagnosis. There is need for earlier diagnosis and treatment, as most patients are severely symptomatic when diagnosed and their mortality is high despite therapy. Screening can help; however, it is not straightforward due to the diversity of patient profiles and lack of sufficiently accurate tools. Echocardiography, currently the best available screening tool, lacks both sensitivity and specificity. The low prevalence of PAH renders many screening tools unfit for purpose. However, this may be overcome, in some instances, by using enrichment tools to preselect screening populations. The majority of data are available for systemic sclerosis. A recent study has demonstrated how lung function can be used to enrich PAH prevalence in a systemic sclerosis population. A screening bundle then selects patients for right heart catheterisation with improved rates of sensitivity compared to current guidelines.

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

    Science.gov (United States)

    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.

  8. 肺动脉高压分类、发病机制及治疗%Classification and pathogensis and treatment of pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    肖谊; 邢西迁; 张红艳; 吴绪伟

    2011-01-01

    肺动脉高压(pulmonary arterial hypertension,PAH)是由多种病因引起并有复杂发病机制的疾病.表现为肺循环的压力和阻力的增加,最终导致右心衰竭,治疗棘手.近年来,PAH的诊断、分类不断更新、完善;发病机制、病理生理、分子生物学的研究不断深入;临床治疗药物也在不断探索.为PAH的诊治开拓了广阔的前景.本文复习文献,对目前PAH研究现状及进展进行阐述.%Pulmonary arterial hypertension (PAH) is a disease by variety of causes,and its pathogensis is complex.In which pulmonary arterial obstruction increases pulmonary vascular resistance,which leads to right ventricular failure,the therapy troublesome.In recent years,The diagnosis and classification of PAH was updated,with deeply researching on the pathogensis,pathophysiology and molecular biology,The treatment is researching constantly.To provide a wide prospect for PAH and diagnosis.This article reviews literature,to explain the recent advances on PAH.

  9. Reproducibility of the ambulatory arterial stiffness index in hypertensive patients

    DEFF Research Database (Denmark)

    Dechering, D.G.; Steen, M.S. van der; Adiyaman, A.;

    2008-01-01

    BACKGROUND: We studied the repeatability of the ambulatory arterial stiffness index (AASI), which can be computed from 24-h blood pressure (BP) recordings as unity minus the regression slope of diastolic on systolic BP. METHODS: One hundred and fifty-two hypertensive outpatients recruited...

  10. [General systems theory, analog models and essential arterial hypertension].

    Science.gov (United States)

    Indovina, I; Bonelli, M

    1991-02-15

    The application of the General System Theory to the fields of biology and particularly of medicine is fraught with many difficulties deriving from the mathematical complexities of application. The authors suggest that these difficulties can be overcome by applying analogical models, thus opening new prospects for the resolution of the manifold problems involved in connection with the study of arterial hypertension.

  11. PHARMACOTHERAPY OF ARTERIAL HYPERTENSION IN ELDERLY PATIENTS: FOCUS ON OCTOGENARIANS

    Directory of Open Access Journals (Sweden)

    E. A. Ushkalova

    2016-01-01

    Full Text Available Pharmacotherapy of arterial hypertension in the elderly is discussed. Russian and international guidelines are presented with a focus on target levels of blood pressure and drugs of choice in these patients. Issues of efficacy and safety of antihypertensive therapy in patients aged 80 years and older are considered.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. SOME ASPECTS OF THE LISINOPRIL USAGE IN ARTERIAL HYPERTENSION TREATMENT

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    N. A. Jaiani

    2010-01-01

    Full Text Available The evidence basis and advantages of the lisinopril usage in a clinical practice as antihypertensive drug are presented. Special attention is paid to organoprotective lisinopril effects and lisinopril implementation at special clinical conditions (chronic obstructive pulmonary disease comorbidity, elderly patients, and concomitant liver diseases. Pharmacoeconomic aspects of lisinopril usage in arterial hypertension are also considered.

  14. Pulmonary arterial hypertension as a manifestation of lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Stark, P.; Sargent, E.N.; Boylen, T.; Jaramillo, D.

    1987-08-01

    We present five patients with systemic lupus erythematosus (SLE) who developed pulmonary arterial hypertension and cor pulmonale in the course of their disease. The clinical features, as well as, the radiological manifestations of this rare manifestation of SLE are discussed. A vasculitic process is the most likely cause of this complication. Therapy is ineffective and the prognosis is poor.

  15. Effect of PAH Specific Therapy on Pulmonary Hemodynamics and Six-Minute Walk Distance in Portopulmonary Hypertension: A Systematic Review and Meta-Analysis

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    Muhammad Faisal

    2014-01-01

    Full Text Available Background. Little is known about the effect of pulmonary arterial hypertension (PAH specific therapy on pulmonary hemodynamics and exercise capacity in patients with portopulmonary hypertension (PoPH because such patients are usually excluded from randomized clinical trials (RCT of such therapy. Methods. We searched PUBMED using the terms “(Therapy/Broad (filter AND (portopulmonary hypertension.” We included studies that met the following criteria: ≥5 patients, AND PoPH confirmed by right heart catheterization (RHC, AND follow-up RHC data, AND/OR baseline and follow-up 6MWD available. Results. 12 studies met our inclusion criteria. None was a RCT. The baseline mPAP was 48.6 ± 4.4 mmHg, cardiac output (CO 5.6 ± 0.9 L/min, and pulmonary vascular resistance (PVR 668.6 ± 219.1 dynes.sec/cm5. The baseline 6MWD was 348.2 ± 35.6 meters. The use of PAH specific therapy improved mPAP by 7.54 mmHg (95% CI 10.2 to 4.9, CO by 1.77 L/min (95% CI 1.1 to 2.4, and PVR by 253 dynes.sec/cm5 (95% CI 291.4 to 214.6 (n=135 and 6MWD by 61.8 meters (95% CI 47.5 to 76 (n=122. Conclusions. The use of PAH specific therapy in PoPH results in significant improvement in both pulmonary hemodynamics and 6MWD.

  16. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: Role of membrane versus nuclear receptors.

    Science.gov (United States)

    Clapp, Lucie H; Gurung, Rijan

    2015-07-01

    Pulmonary arterial hypertension (PAH) is a progressive disease of distal pulmonary arteries in which patients suffer from elevated pulmonary arterial pressure, extensive vascular remodelling and right ventricular failure. To date prostacyclin (PGI2) therapy remains the most efficacious treatment for PAH and is the only approved monotherapy to have a positive impact on long-term survival. A key thing to note is that improvement exceeds that predicted from vasodilator testing strongly suggesting that additional mechanisms contribute to the therapeutic benefit of prostacyclins in PAH. Given these agents have potent antiproliferative, anti-inflammatory and endothelial regenerating properties suggests therapeutic benefit might result from a slowing, stabilization or even some reversal of vascular remodelling in vivo. This review discusses evidence that the pharmacology of each prostacyclin (IP) receptor agonist so far developed is distinct, with non-IP receptor targets clearly contributing to the therapeutic and side effect profile of PGI2 (EP3), iloprost (EP1), treprostinil (EP2, DP1) along with a family of nuclear receptors known as peroxisome proliferator-activated receptors (PPARs), to which PGI2 and some analogues directly bind. These targets are functionally expressed to varying degrees in arteries, veins, platelets, fibroblasts and inflammatory cells and are likely to be involved in the biological actions of prostacylins. Recently, a highly selective IP agonist, selexipag has been developed for PAH. This agent should prove useful in distinguishing IP from other prostanoid receptors or PPAR binding effects in human tissue. It remains to be determined whether selectivity for the IP receptor gives rise to a superior or inferior clinical benefit in PAH.

  17. [Chronobiology of blood pressure and chronopharmacotherapy of arterial hypertension].

    Science.gov (United States)

    Schmieder, R E; Bramlage, P; Schunkert, H

    2012-02-01

    Arterial blood pressure is subject to a circadian rhythm that results in a fall of blood pressure during the night. In patients with diabetes, renal insufficiency, left-ventricular hypertrophy, sleep apnea, hypertension of pregnancy, and different forms of secondary hypertension a nocturnal fall of blood pressure is even abandoned or reverted. Diagnosis is made using 24-h blood pressure measurement, which is however used not frequently enough for a clinical assessment or adjustment of therapy. An adaption of the selection or the time of administration of antihypertensive drugs with respect to the circadian rhythm is beneficial to control blood pressure and reduce cardiovascular morbidity. This is particularly true for patients with an a non- or inverted dipping blood pressure pattern, in which the bedtime dosing may result in a normalization of blood pressure and restoration of a normal circadian rhythm. The present manuscript reviews the chronopharmacotherapy of arterial hypertension and grant practical recommendations for their translation into clinical practice.

  18. The arterial load in pulmonary hypertension

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    A. Vonk-Noordegraaf

    2010-09-01

    Full Text Available The anatomical differences between the pulmonary and systemic arterial system are the main cause of the difference in distribution of compliance. In the pulmonary arterial system compliance is distributed over the entire arterial system, and stands at the basis of the constancy of the RC-time. This distribution depends on the number of peripheral vessels, which is ∼8–10 times more in the pulmonary system than the systemic tree. In the systemic arterial tree the compliance is mainly located in the aorta (80% of total compliance in thoracic-abdominal aorta. The constant RC-time in the pulmonary bed results in proportionality of systolic and diastolic pressure with mean pressure and, in turn, in the constant ratio of oscillatory and mean power.

  19. Lineage Analysis in Pulmonary Arterial Hypertension

    Science.gov (United States)

    2013-06-01

    endothelial cells 12, 13. At the level of small pulmonary arteries, the occlusion by neointimal formation significantly exceeds muscularization of the...pyrrole. A, B) Normal muscular pulmonary artery (PA) adjacent to bronchiole (Br) A) hematoxylin and eosin stain (H&E), B) elastin-van Gieson stain (EVG...Iyer NV, Huso DL, Sun X, McWilliams R, Beaty T, Sham JS, Wiener CM, Sylvester JT, Semenza GL. Impaired physiological responses to chronic hypoxia in

  20. Pathophysiological Mechanisms on Treating Pulmonary Arterial Hypertension with Artemisinine%青蒿素治疗肺动脉高压的病理生理机制

    Institute of Scientific and Technical Information of China (English)

    文宏

    2011-01-01

    肺动脉高压(PAH)是以肺动脉压力升高和肺动脉重构为特征的病理生理综合征.由于其发病机制较为复杂,目前尚无有效的治愈措施,预后差.如何有效降低PAH的肺动脉压力,减轻或逆转肺动脉重构,改善患者的预后已成为PAH治疗领域的研究热点.现就青蒿素在PAH治疗中可能的保护性病理生理机制予以综述,旨在探讨青蒿素防治PAH的理论基础.%Pulmonary arterial hypertension is a pathophysiological syndrome characterized by high pulmonary arterial pressure and pulmonary arterial remodeling. Due to its complex pathogenesis, at present , there is no effective healing treatment and the prognosis is poor. How to effectively decrease the pulmonary arterial pressure, alleviating or reversing the pulmonary arterial remodeling and improving the prognosis is becoming the hot topics in the field of PAH treatment. The protective pathophysiological mechanisms on treating pulmonary arterial hypertension with artemisinine is reviewed,in aiming to study its pharmacological foundation of the prevention with PAH.

  1. Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension

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    Bianca Marasini

    2005-01-01

    Full Text Available Fractalkine (FKN and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc and pulmonary arterial hypertension (PAH. Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively. The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively. In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.

  2. An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

    Science.gov (United States)

    Navas Tejedor, P; Tenorio Castaño, J; Palomino Doza, J; Arias Lajara, P; Gordo Trujillo, G; López Meseguer, M; Román Broto, A; Lapunzina Abadía, P; Escribano Subía, P

    2017-03-01

    Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.

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

    Science.gov (United States)

    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.

  4. Existing drugs and agents under investigation for pulmonary arterial hypertension.

    Science.gov (United States)

    Sharma, Mala; Pinnamaneni, Sowmya; Aronow, Wilbert S; Jozwik, Bartosz; Frishman, William H

    2014-01-01

    Pulmonary arterial hypertension is a progressive and debilitating disorder with an associated high morbidity and mortality rate. Significant advances in our understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary hypertension have occurred over the past several decades. This has allowed the development of new therapeutic options in this disease. Today, our selection of therapeutic modalities is broader, including calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase inhibitors, and soluble guanylate cyclase stimulators, but the disease remains fatal. This underscores the need for a continued search for novel therapies. Several potential pharmacologic agents for the treatment of pulmonary arterial hypertension are under clinical development and some promising results with these treatments have been reported. These agents include rho-kinase inhibitors, long-acting nonprostanoid prostacyclin receptor agonists, tyrosine protein kinase inhibitors, endothelial nitric oxide synthase couplers, synthetically produced vasoactive intestinal peptide, antagonists of the 5-HT2 receptors, and others. This article will review several of these promising new therapies and will discuss the current evidence regarding their potential benefit in pulmonary arterial hypertension.

  5. Sildenafil for the Treatment of Pulmonary Arterial Hypertension in Infants with Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Trottier-Boucher, M N; Lapointe, A; Malo, J; Fournier, A; Raboisson, M J; Martin, B; Moussa, A

    2015-08-01

    Sildenafil, a phosphodiesterase-5 inhibitor, is a controversial treatment option for pulmonary arterial hypertension (PAH), a significant complication of bronchopulmonary dysplasia (BPD). The objective of this study was to evaluate the use of sildenafil in infants with PAH secondary to BPD. This was a retrospective review of medical records of all premature infants with PAH associated with BPD treated with sildenafil between January 2009 and May 2013 in a level 3 neonatal intensive care unit. The primary outcomes were clinical response (20 % decreases in respiratory support score or oxygen requirements) and echocardiographic response (20 % decrease in tricuspid regurgitation gradient or change of at least 1° of septal flattening). Twenty-three infants were included in the study. Significant echocardiographic and clinical responses were, respectively, observed in 71 and 35 % of cases. Most clinical responses were observed in the first 48 h of treatment, and the median time to an echocardiographic response was of 19 days. The median dose of sildenafil used was 4.4 mg/kg/day, with a median time to reach the maximum dose of 9 days. Transient hypotension was the primary reported side effect, and it was observed in 44 % of our study population. Sildenafil treatment in patients with PAH secondary to BPD was associated with an echocardiographic improvement in the majority of patients, whereas clinical improvement was observed in a minority of patients. Many infants presented with transient hypotension during the course of the treatment. Further prospective studies are required to better assess safety and efficacy of this treatment in this population.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Coordinated modulation of circulating miR-21 in HIV, HIV-associated pulmonary arterial hypertension, and HIV/HCV co-infection

    Science.gov (United States)

    Parikh, Victoria N.; Park, Joseph; Nikolic, Ivana; Channick, Richard; Yu, Paul B.; De Marco, Teresa; Hsue, Priscilla; Chan, Stephen Y.

    2015-01-01

    Dysregulation of microRNA-21 (miR-21) is independently associated with human immunodeficiency virus (HIV) infection, pulmonary arterial hypertension (PAH), and hepatitis C virus (HCV) infection. To assess expression of miR-21 in these overlapping comorbidities, we measured plasma miR-21 in HIV with and without PAH and then stratified by concomitant HCV infection. miR-21 was increased in HIV and HIV-PAH versus uninfected subjects, but did not differ between these groups. HIV/HCV co-infection correlated with even higher miR-21 levels within the HIV-infected population. These data reveal specific regulation of plasma miR-21 in HIV, HIV/HCV co-infection, and PAH and suggest that miR-21 may integrate complex disease-specific signaling in the setting of HIV infection. PMID:26473639

  8. Statins and pulmonary arterial hypertension%他汀类药物与肺动脉高压

    Institute of Scientific and Technical Information of China (English)

    邱海艳; 陶一江; 马航

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a progressive and often fatal disease characterized by vascular obstruction and vasoconstriction,leading to persistent elevation of pulmonary arterial resistance and right-sided heart failure.PAH is classified into primary and secondary forms.Its pathogenesis is still not very clear,but the basic pathological alteration of pulmonary hypertension contains three dependent elements:pulmonary vasoconstriction,pulmonary vascular remodeling and pulmonary microvascular thrombogenesis.Statins have been shown to both prevent and attenuate pulmonary hypertension in animal models and this was associated with increased apoptosis and reduced proliferation of smooth muscle cells,inhibit inflammation response,anti-oxidation and so on.Therefore,statins have been considered as a therapeutic option in PAH based on the pathogenesis of the disease and the pleiotropic actions that these agents exert.The researches using statins to treat pulmonary hypertension were reviewed and the possible mechanisms were postulated.They provide a theoretical basis for statins in the treatment of pulmonary hypertension.%肺动脉高压(PAH)是以血管阻塞和血管收缩为特征,呈进行性发展,并最终导致持续性肺动脉阻力增加和右心衰竭的一种疾病.PAH分为原发性和继发性两大类型,其发病机制至今尚不非常明确,基本病理改变有三个方面:肺血管收缩、血管重塑、原位血栓的形成.许多动物实验证实他汀类药物可能通过抑制细胞增殖、诱导细胞凋亡、抑制炎症反应、抗氧化等多种作用预防和缓解PAH.因此基于疾病的发病机制和药物的多效性,他汀类药物已经被认为是治疗PAH的一种有利选择.现对他汀类药物在PAH治疗中的研究现况进行综述,并探讨其可能作用机制,为他汀类药物在PAH的治疗中提供理论依据.

  9. Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels

    Institute of Scientific and Technical Information of China (English)

    LI Gang; XU Yu-lin; LING Feng; LIU Ai-jun; WANG Dong; WANG Qiang; LIU Ying-long

    2012-01-01

    Background Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH).Angiotensin-converting enzyme 2 (ACE2),a primary component of the vasoprotective axis in RAS,is recently identified that it has regulatory actions in lung pathophysiology,but the mechanism in these processes is uncertain yet.Methods Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats.The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR),Western blotting and fluorogenic peptide assay.Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection.The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established.Results Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment.The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection,and the rats developed severe PAH in 21 days with high PAP,right ventricular hypertrophy and neointimal formation.Treatment with resorcinolnaphthalein prevented these features.Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α,monocyte chemoattractant protein-1 (MCP-1),interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis.Conclusions These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti

  10. 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

  11. 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.

  12. Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension

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    Xue Jiang

    2015-11-01

    Full Text Available Background/Aims: To investigaterole of serotonin (5-HT and serotonin transporter (5-HTT in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH and the effect of statins on regulating 5HT and 5-HTT. Methods: A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day. After 16 weeks of cigarette smoke exposure, body weight and mean pulmonary arterial pressure (mPAP were measured, bronchoalveolar lavage (BAL was performed, and lung tissues and blood samples were collected to determine cardiopulmonary pathology, physiological indices, blood levelof 5-HT and expression of 5-HTT in the lung. Results: In addition to alveolar structural damage (COPD-like injury, chronic cigarette smoke exposure lead to pulmonary artery remodeling and PAH as evidenced by significant elevation of mPAP, RVHI, WT%and WA%. Cigarette smoke exposure resulted in significant reduction in animal body weight, and simvastatin significantly prevented smoke-induced weight loss. The number of inflammatory cells in BALF was dramatically increased in smoke exposed rats, and simvastatin dampened the number of leukocytes, neutrophils, lymphocytes, and macrophages. In addition, circulating 5-HTand expression of 5-HTT in the lung were significantly increased in the smoked rats compared to control rats, and it was significantly reduced by simvastatin. Alteration of BALF inflammatory cells, 5-HT and 5-HTT was significantly correlated with changes of mPAP, RVHI, WT% and WA%. Conclusions: Cigarette smoke exposure could result in not only COPD, but also PAH, which may attribute to the alteration of blood 5-HT and lung tissue 5-HTT. Simvastatin could significantly inhibited 5-HT and 5-HTT expression, and by which mechanism, it may protect animals from development

  13. Autoimmune rheumatic disease and pulmonary arterial hypertension%免疫风湿病与肺动脉高压

    Institute of Scientific and Technical Information of China (English)

    何岚

    2009-01-01

    @@ 肺动脉高压(pulmonary arterial hypertension.PAH)是一种进展迅速、预后极差的疾病.如果不治疗,40%~60%的患者在诊断后2年内死亡.PAH除原因不清的特发性PAH和家族性PAH外,多种临床疾病状态与PAH的发生有关.免疫风湿病(autoimmune rheumatic disease,AIRD)是一组与PAH发生多个环节相关的疾病[1-2].

  14. Tissue Doppler Findings in Patients with Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Firoozeh Abtahi

    2016-09-01

    Full Text Available In conclusion, our results suggested that increasing degrees of pulmonary artery systolic pressure affected timing of some tissue Doppler-derived intervals within the cardiac cycle, including IVC time, time to peak systolic myocardial velocity (Sm, and time to peak strain. Therefore, tissue Doppler imaging could be used in assessment of patients with suspected pulmonary arterial hypertension. Background: Pulmonary hypertension is an untreatable condition with poor prognosis and factors such as more elevated pulmonary arterial systolic pressure and right ventricular dysfunction are associated with a worse outcome. Objectives: Considering the limitations of the current modalities, this study aimed to find the relationship between tissue Doppler-derived systolic and diastolic parameters and elevated pulmonary arterial pressure in order to assess the routine application of tissue Doppler imaging in evaluation of pulmonary arterial hypertension. Patients and Methods: This study was conducted on 100 inpatient and outpatient individuals referred to the Department of Echocardiography in Shahid Faghihi hospital, Shiraz, Iran from July 2012 to March 2013. The individuals who had preserved right ventricular function in the presence of pulmonary arterial hypertension were included in the case group. On the other hand, the patients who did not have echocardiographic signs of pulmonary arterial hypertension were enrolled into the control group. All the patients underwent a complete transthoracic echocardiogram including 2-dimensional, color flow, and spectral Doppler as well as tissue Doppler imaging using a vivid E9 system, and the desired systolic and diastolic parameters were recorded. The relationship among these parameters was evaluated by independent sample t-test using the SPSS statistical software, version 16. Besides, P < 0.05 was considered to be statistically significant. Results: The mean time to peak strain was significantly longer in the case

  15. Effects of iloprost combined with low dose tadalafil in adult congenital heart disease patients with severe pulmonary arterial hypertension: a single-center,open-label controlled study

    Institute of Scientific and Technical Information of China (English)

    张曹进

    2014-01-01

    Objective To evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease(CHD)patients with severe pulmonary arterial hypertension(PAH).Methods Adult CHD patients with severe PAH were included and divided into the sequential combination therapy group[iloprost:10μg/inhalation,6 times per day for 6 months,and then add oral tadalafil(5 mg/d)till 12 months,n=32]and upfront combination therapy group[iloprost:10μg/inhalation,6 times per day combined with oral tadalafil(5 mg)

  16. Computational model of collagen turnover in carotid arteries during hypertension.

    Science.gov (United States)

    Sáez, P; Peña, E; Tarbell, J M; Martínez, M A

    2015-02-01

    It is well known that biological tissues adapt their properties because of different mechanical and chemical stimuli. The goal of this work is to study the collagen turnover in the arterial tissue of hypertensive patients through a coupled computational mechano-chemical model. Although it has been widely studied experimentally, computational models dealing with the mechano-chemical approach are not. The present approach can be extended easily to study other aspects of bone remodeling or collagen degradation in heart diseases. The model can be divided into three different stages. First, we study the smooth muscle cell synthesis of different biological substances due to over-stretching during hypertension. Next, we study the mass-transport of these substances along the arterial wall. The last step is to compute the turnover of collagen based on the amount of these substances in the arterial wall which interact with each other to modify the turnover rate of collagen. We simulate this process in a finite element model of a real human carotid artery. The final results show the well-known stiffening of the arterial wall due to the increase in the collagen content.

  17. Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension

    Directory of Open Access Journals (Sweden)

    Palatini P

    2011-12-01

    Full Text Available Paolo Palatini1, Edoardo Casiglia1, Jerzy Gąsowski2, Jerzy Głuszek3, Piotr Jankowski4, Krzysztof Narkiewicz5, Francesca Saladini1, Katarzyna Stolarz-Skrzypek4, Valérie Tikhonoff1, Luc Van Bortel6, Wiktoria Wojciechowska4, Kalina Kawecka-Jaszcz41Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy; 2Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Kraków, Poland; 3Department of Arterial Hypertension, University Hospital, Poznan, Poland; 4First Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland; 5Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland; 6Heymans Institute of Pharmacology, Ghent University, Ghent, BelgiumAbstract: This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP

  18. An update on the role of adipokines in arterial stiffness and hypertension.

    Science.gov (United States)

    Sabbatini, Andréa R; Fontana, Vanessa; Laurent, Stephane; Moreno, Heitor

    2015-03-01

    Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN).

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

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  1. Retroperitoneal Paraganglioma – a rare cause of arterial hypertension

    Directory of Open Access Journals (Sweden)

    Isabel Silva

    2017-03-01

    Full Text Available Paragangliomas are rare neuroendocrine tumours, most commonly found in adults. These differ from pheochromocytomas in that their location is extra-adrenal, and they are responsible for about 1% of arterial hypertension aetiologies. We report the case of a 30-year-old female whose past medical history was unremarkable. However, her arterial hypertension led to further examination in search of secondary aetiologies, in which a retroperitoneal mass and an increase in levels of catecholamines were detected; findings that led to the final diagnosis of paraganglioma. A multidisciplinary team, whose approach was to use pharmacological alpha-adrenergic blocking agents and a surgical resection of the lesion, treated the patient. The patient is clinically well but will continue to be monitored as an outpatient, and genetic testing is being encouraged.

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

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc

    2005-02-12

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

  3. Nesiritide for pulmonary arterial hypertension with decompensated cor pulmonale.

    Science.gov (United States)

    Kingman, Martha S; Thompson, Brenda S; Newkirk, Trixie; Torres, Fernando

    2005-01-01

    Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.

  4. Selexipag for the Treatment of Pulmonary Arterial Hypertension

    DEFF Research Database (Denmark)

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

    2015-01-01

    regimen prematurely because of adverse events. The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain. CONCLUSIONS: Among patients with pulmonary arterial hypertension, the risk of the primary......-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period (defined for each patient as 7 days after the date of the last intake of selexipag...... and hospitalization accounted for 81.9% of the events. The effect of selexipag with respect to the primary end point was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving treatment at baseline (including those...

  5. Midterm results of diagnostic treatment and repair strategy in older patients presenting with nonrestrictive ventricular septal defect and severe pulmonary artery hypertension

    Institute of Scientific and Technical Information of China (English)

    Liu Aijun; Li Zhiqiang; Li Xiaofeng; Fan Xiangming; Su Junwu; Zhang Jing; He Yan

    2014-01-01

    Background Congenital heart disease with severe pulmonary arterial hypertension (SPAH),previously thought to have irreversible pulmonary vascular disease (PVD),has been recently successfully corrected using diagnostic treatment and repair strategy by our surgery team.This study aimed to evaluate the midterm results of a selected cohort of older patients with nonrestrictive ventricular septal defect (VSD) and SPAH using diagnostic treatment and repair strategy.Methods The records of 56 patients older than six years with nonrestrictive VSD and SPAH undergoing diagnostic treatment and repair strategy from 2006 to 2012 were retrospectively reviewed.All patients received advanced pulmonary arterial hypertension (PAH) therapy and radical repairs were performed when transcutaneous oxygen saturation (SPO2) increased up to 93%.Results There were no operative deaths.SPO2 and baseline six-minute walk test (SMWT) distance of all selected patients increased significantly and mean pulmonary artery pressure (MPAP) regressed significantly after diagnostic treatment and at late follow-up (P <0.01).The incidence of late postoperative PAH was seen in six (10.7%) patients and by Logistic regression analysis,early postoperative PAH was an independent risk factor related to late postoperative PAH.Conclusions Diagnostic treatment and repair strategy was effective and safe for treatment of nonrestrictive VSD and SPAH and the midterm results were excellent.Diagnostic treatment strategy was effective in assessing the reversibility of SPAH in older patients associated with nonrestrictive VSD and the PVD in these selective patients is generally reversible.

  6. [Arterial hypertension among adolescents in Rio de Janeiro: prevalence and association with physical activity and obesity].

    Science.gov (United States)

    Corrêa-Neto, Victor Gonçalves; Sperandei, Sandro; Silva, Luis Aureliano Imbiriba; Maranhão-Neto, Geraldo de Albuquerque; Palma, Alexandre

    2014-06-01

    The scope of this study was to identify the prevalence of systemic arterial hypertension among adolescent students (aged 17-19 years) in the third and final year of high school in state schools in the municipality of Rio de Janeiro, and to investigate associations between systemic arterial hypertension and obesity and physical activity levels. Data on arterial pressure, body mass index and physical activity were gathered. The analysis included 854 individuals. Descriptive statistical analysis was applied to the sample, along with a Poisson regression model to determine the impact of the variables on the prevalence of systemic arterial hypertension. The prevalence of systemic arterial hypertension was 19.4%. Male sex, overweight and obesity presented significant positive associations with systemic arterial hypertension (p arterial hypertension (p > 0.05). The nature of these relationships should be interpreted in the light of reflection and not of passive labeling based on hegemonic concepts.

  7. Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    K. Stefanantoni

    2015-03-01

    Full Text Available Pulmonary arterial hypertension (PAH can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc. Macrophage migration inhibitory factor (MIF is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor β (SCGF β is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg. MIF and SCGF β levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF β in patients with idiopathic PAH (P=0.03 and P=0.004 and with PAH secondary to SSc (P=0.018 and P=0.023 compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA class (P=0.03. We can hypothesize that MIF and SCGF β are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease.

  8. [Treatment of arterial hypertension in pregnancy in relation to current guidelines of the Polish Society of Arterial Hypertension from 2011].

    Science.gov (United States)

    Szczepaniak-Chicheł, Ludwina; Tykarski, Andrzej

    2012-10-01

    Arterial hypertension concerns 7-10% of pregnancies and leads to an increased risk of complications for both, the mother and the child. This rate will probably rise in the years to come due to the notable tendency among women to delay the decision to become pregnant - values of blood pressure and occurrence of arterial hypertension increase with age, as well as due to the growing problem of obesity resulting from inappropriate dietary habits and lack of regular everyday physical activity. Difficulties with management of that clinical condition are partly related with lack of unified and widely accepted guidelines. Different opinions in the subject of terminology and classification of pregnancy hypertension or indications for pharmacotherapy as well as choice of the optimal antihypertensive drug, emerge from objective causes such as combination of various pathogenetic factors typical for arterial hypertension itself and those connected with pregnancy elsewhere stressed priorities of therapy from the point of view of the health of the mother and of the fetus, as well as lack of randomized clinical trials due to obvious ethical purposes, but also from the fact that pregnancy hypertension is a focus of attention for different specialists - obstetricians, hypertensiologists and perinatologists. A good cooperation regarding experience and information among all of these specializations would be the most beneficial for pregnant women and their children. Lack of new modern antihypertensive agents, safe and effective in pregnancy while the older ones are being withdrawn from the market as their production is no longer cost-effective for pharmacological companies, has become an increasing problem in many countries, and Poland among them. The aim of the following publication was to present the statement on management of pregnancy hypertension from the current guidelines of the Polish Society of Arterial Hypertension 2011 to gynecologists and obstetricians, with a commentary

  9. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    Science.gov (United States)

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction.

  10. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Jensen, J S; Feldt-Rasmussen, B; Strandgaard, S

    2000-01-01

    Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among...... hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease......, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person...

  11. Intravenous Epoprostenol for Management of Pulmonary Arterial Hypertension during Pregnancy

    Directory of Open Access Journals (Sweden)

    Julia Timofeev

    2013-10-01

    Full Text Available Background - Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report - We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion - Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown.

  12. Intravenous Epoprostenol for Management of Pulmonary Arterial Hypertension during Pregnancy.

    Science.gov (United States)

    Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W

    2013-10-01

    Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown.

  13. Methamphetamine Use and Pulmonary Hypertension

    Science.gov (United States)

    ... other problems, diagnosing a case of pulmonary hyper- tension can be difficult and may require a specialist. Once pulmonary hyperten- sion is diagnosed, however, treatment can begin immediately. One form of PH is called pulmonary arterial hypertension (PAH). In PAH, the blood vessels that ...

  14. 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...

  15. Bloodstream infections among patients treated with intravenous epoprostenol or intravenous treprostinil for pulmonary arterial hypertension--seven sites, United States, 2003-2006.

    Science.gov (United States)

    2007-03-02

    Pulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by elevated pulmonary artery pressure and pulmonary vascular resistance. Continuous infusion of a prostanoid, which acts as a vasodilator and anti-proliferative agent, is indicated in the treatment of patients with severe PAH. Two prostanoids are approved for intravenous (IV) use in the United States: epoprostenol (epoprostenol sodium [brand name Flolan], Gilead, Foster City, California) and treprostinil (treprostinil sodium [brand name Remodulin], United Therapeutics, Silver Spring, Maryland). These drugs are administered to PAH patients at hundreds of treatment centers in the United States. In September 2006, CDC received a report from a PAH specialist of a suspected increase in the number of gram-negative bloodstream infections (BSIs) among PAH patients treated with IV treprostinil. CDC conducted a retrospective investigation with the assistance of several state health departments and the cooperation of seven PAH treatment centers to determine the relative rates of BSI in a sample of patients treated with IV treprostinil and IV epoprostenol during 2003--2006. This report describes the results of that investigation, which indicated that, based on combined data from seven separate PAH treatment centers, pooled mean rates of BSI (primarily gram-negative BSI) were significantly higher for patients on treprostinil than for those on epoprostenol. The results do not suggest intrinsic contamination of IV treprostinil as a cause of the infections; the difference in rates might have been caused by differences in preparation and storage of the two agents, differences in catheter care practices, or differences in the anti-inflammatory activity of the agents. Health-care providers who care for PAH patients should be aware of these findings. Further investigation is needed to determine the causes of the different infection rates at centers where this was observed and to determine whether such a

  16. [Treatment of pulmonary arterial hypertension in children].

    Science.gov (United States)

    Fraisse, A; Habib, G

    2004-08-01

    Treatment strategies for pulmonary hypertension in children have dramatically evolved. Traditional therapy with calcium channel blockers and pulmonary transplantation is only indicated in selected patients and does not reduce mortality very significantly. New pulmonary vasodilators are emerging from recent trials in the adult population. Their indications are based on the patient's NYHA classification. The epoprostenol (prostacyclin, Flolan) has shown reduction in mortality and improvement in functional symptoms in pediatric patients. The frequent side effects and continuous intravenous infusion limit the indication of prostacyclin in NYHA class IV children. The endothelin receptor blocker bosentan (Tracleer) is an orally given agent. It improves functional symptoms in adults and hemodynamic measures in children. It can be started in children with moderate functional symptoms (NYHA class II and III). The type V phosphodiesterase inhibitor sildenafil (Viagra) is being evaluated and may represent a promising therapy in the future. Invasive strategies like catheter-based atrial septostomy may be useful in particular cases. Randomized-controlled studies are urgently needed to evaluate the safety and efficacy of these new therapies.

  17. Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability

    Directory of Open Access Journals (Sweden)

    Khrystyna Semen

    2016-04-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare multifactorial disease with an unfavorable prognosis. Sildenafil therapy can improve functional capacity and pulmonary hemodynamics in PAH patients. Nowadays, it is increasingly recognized that the effects of sildenafil are pleiotropic and may also involve changes of the pro-/antioxidant balance, lipid peroxidation and autonomic control. In present study we aimed to assess the effects of sildenafil on the fatty acids (FAs status, level of hydroxynonenal (HNE and heart rate variability (HRV in PAH patients. Patients with PAH were characterized by an increase in HNE and changes in the FAs composition with elevation of linoleic, oleic, docosahexanoic acids in phospholipids as well as reduced HRV with sympathetic predominance. Sildenafil therapy improved exercise capacity and pulmonary hemodynamics and reduced NT-proBNP level in PAH. Antioxidant and anti-inflammatory effects of sildenafil were noted from the significant lowering of HNE level and reduction of the phopholipid derived oleic, linoleic, docosahexanoic, docosapentanoic FAs. That was also associated with some improvement of HRV on account of the activation of the neurohumoral regulatory component. Incomplete recovery of the functional metabolic disorders in PAH patients may be assumed from the persistent increase in free FAs, reduced HRV with the sympathetic predominance in the spectral structure after treatment comparing to control group. The possibilities to improve PAH treatment efficacy through mild stimulation of free radical reactions and formation of hormetic reaction in the context of improved NO signaling are discussed.

  18. Hipertensão arterial na infância Arterial hypertension in childhood

    Directory of Open Access Journals (Sweden)

    Cláudia Maria Salgado

    2003-06-01

    Full Text Available OBJETIVOS: realizar uma revisão crítica da literatura atual, enfocando aspectos práticos e relevantes para o diagnóstico e tratamento ambulatorial da criança com hipertensão arterial. FONTE DE DADOS: artigos clássicos e revisão sistemática da literatura atual através de busca eletrônica nos bancos de dados Medline e Lilacs, nos últimos 10 anos, utilizando-se as palavras-chave hipertensão arterial, recém-nascido, lactente, pré-escolar, criança e adolescente, selecionando-se aqueles que trouxeram informações relevantes. SÍNTESE DOS DADOS: a hipertensão arterial e a obesidade são um problema de saúde pública em todo o mundo. A hipertensão arterial essencial do adulto inicia-se na infância, e, além disso, pode ser secundária a várias doenças. O pediatra tem por obrigação medir adequadamente a pressão arterial de seus pacientes. Quando descoberta, a hipertensão arterial deve ser investigada para ser adequadamente tratada. A investigação depende da idade e do grau de elevação da pressão arterial, devendo preocupar-se não somente com a causa da hipertensão, mas também com os seus efeitos em órgãos alvo. CONCLUSÕES: o reconhecimento precoce da pressão arterial anormal e a intervenção (investigação e tratamento adequada são necessários para diminuir a morbidade/mortalidade cardiovascular e renal futura.OBJECTIVE: to critically review recent medical literature, focusing on practical features that are relevant for diagnosis and outpatient treatment of pediatric hypertension. SOURCES OF DATA: classic articles and systematic review of recent literature through electronic search of Medline and Lilacs databases over the last 10 years, using the key words arterial hypertension, newborns, infants, preschool, children and adolescents. Those articles containing relevant information were selected. SUMMARY OF THE FINDINGS: arterial hypertension and obesity are public health problems all over the world. Essential

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

    Science.gov (United States)

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

    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(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.

  20. 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.)

  1. A novel break point of the BMPR2 gene exonic deletion in a patient with pulmonary arterial hypertension.

    Science.gov (United States)

    Aimi, Yuki; Hirayama, Tomomi; Kataoka, Masaharu; Momose, Yuichi; Nishimaki, Saiko; Matsushita, Kenichi; Yoshino, Hideaki; Satoh, Toru; Gamou, Shinobu

    2013-12-01

    The presence of genetic rearrangements of bone morphogenetic protein type 2 receptor (BMPR2) was identified in pulmonary arterial hypertension (PAH) patients as the deletion or duplication of one or more exons of the gene. We recently investigated the deletion break points in exonic deletions of BMPR2 in two Japanese familial cases with PAH, and found that these were Alu-mediated via either non-allelic homologous recombination or non-homologous recombination. We herein report the third case of exonic deletion, which was in a 25-year-old female PAH patient with a deletion of BMPR2 exon 3. The break point in this case was not located in an Alu sequence. The 5'- and 3'-break point maps between the inverted Alu sequences in intron 2 and in exon 3, respectively, resulted in a 759-bp deletion. This novel exonic deletion in this PAH case may be a unique and non-recurrent rearrangement, and appears to be of a different size from that in other patients.

  2. In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension

    Institute of Scientific and Technical Information of China (English)

    陶军; 靳亚非; 王礼春; 唐安丽; 廖新学; 杨震; 马虹

    2003-01-01

    Objective To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension. Methods Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model.Results The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased. Conclusion In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.

  3. Hemodynamic response to treatment of iron deficiency anemia in pulmonary arterial hypertension: longitudinal insights from an implantable hemodynamic monitor.

    Science.gov (United States)

    Mehmood, Muddassir; Agarwal, Richa; Raina, Amresh; Correa-Jaque, Priscilla; Benza, Raymond L

    2016-12-01

    Despite new therapeutic options, pulmonary arterial hypertension (PAH) remains a progressive disease associated with substantial morbidity and mortality. As such, additional strategies for monitoring and adjunctive management of this disease are important. A 59-year-old woman with scleroderma-associated PAH received an implantable hemodynamic monitor (IHM) as part of a research protocol at our institution. Pulmonary artery pressures, heart rate, and cardiac output (sensor-based algorithm) were measured on a daily basis, and parameters of right ventricular (RV) performance and afterload were calculated. At the time of IHM implant, the patient had functional class III symptoms, was receiving triple-drug therapy, and had normal hemoglobin levels. Four months after implant, and with further optimization of prostacyclin therapy, she had improvement in her symptoms. However, shortly thereafter, while the patient was receiving stable drug therapy, her case regressed with worsening symptoms, and the patient received a new diagnosis of iron deficiency anemia. Oral iron supplementation resulted in normalization of hemoglobin levels and improvement in the patient's iron profile. A gradual and sustained reduction in pulmonary pressures was noted after initiation of oral iron accompanied by increased RV performance and favorable reduction in RV afterload. The patient had significant symptomatic improvement. Iron deficiency is an underappreciated yet easily treatable risk factor in PAH. Use of IHM in this case longitudinally illustrates the optimization of pulmonary hemodynamics and RV afterload in tandem with clinical improvement achieved by a simple therapy.

  4. Hemodynamic response to treatment of iron deficiency anemia in pulmonary arterial hypertension: longitudinal insights from an implantable hemodynamic monitor

    Science.gov (United States)

    2016-01-01

    Abstract Despite new therapeutic options, pulmonary arterial hypertension (PAH) remains a progressive disease associated with substantial morbidity and mortality. As such, additional strategies for monitoring and adjunctive management of this disease are important. A 59-year-old woman with scleroderma-associated PAH received an implantable hemodynamic monitor (IHM) as part of a research protocol at our institution. Pulmonary artery pressures, heart rate, and cardiac output (sensor-based algorithm) were measured on a daily basis, and parameters of right ventricular (RV) performance and afterload were calculated. At the time of IHM implant, the patient had functional class III symptoms, was receiving triple-drug therapy, and had normal hemoglobin levels. Four months after implant, and with further optimization of prostacyclin therapy, she had improvement in her symptoms. However, shortly thereafter, while the patient was receiving stable drug therapy, her case regressed with worsening symptoms, and the patient received a new diagnosis of iron deficiency anemia. Oral iron supplementation resulted in normalization of hemoglobin levels and improvement in the patient’s iron profile. A gradual and sustained reduction in pulmonary pressures was noted after initiation of oral iron accompanied by increased RV performance and favorable reduction in RV afterload. The patient had significant symptomatic improvement. Iron deficiency is an underappreciated yet easily treatable risk factor in PAH. Use of IHM in this case longitudinally illustrates the optimization of pulmonary hemodynamics and RV afterload in tandem with clinical improvement achieved by a simple therapy. PMID:28090307

  5. 1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Taijie Lin

    2016-01-01

    Full Text Available Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT induced pulmonary arterial hypertension (PAH. Methods. Forty male Sprague-Dawley (SD rats were randomly divided into 5 groups (n=8, each. PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0 served as control. Mean pulmonary arterial pressure (mPAP was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA and orthogonal partial least-squares discriminant analysis (OPLS-DA were used to discriminate different metabolic profiles. Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis. Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

  6. [Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

    Science.gov (United States)

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

  7. Phosphodiesterase 5 inhibitors augment UT-15C-stimulated ATP release from erythrocytes of humans with pulmonary arterial hypertension.

    Science.gov (United States)

    Bowles, Elizabeth A; Moody, Gina N; Yeragunta, Yashaswini; Stephenson, Alan H; Ellsworth, Mary L; Sprague, Randy S

    2015-01-01

    Both prostacyclin analogs and phosphodiesterase 5 (PDE5) inhibitors are effective treatments for pulmonary arterial hypertension (PAH). In addition to direct effects on vascular smooth muscle, prostacyclin analogs increase cAMP levels and ATP release from healthy human erythrocytes. We hypothesized that UT-15C, an orally available form of the prostacyclin analog, treprostinil, would stimulate ATP release from erythrocytes of humans with PAH and that this release would be augmented by PDE5 inhibitors. Erythrocytes were isolated and the effect of UT-15C on cAMP levels and ATP release were measured in the presence and absence of the PDE5 inhibitors, zaprinast or tadalafil. In addition, the ability of a soluble guanylyl cyclase inhibitor to prevent the effects of tadalafil was determined. Erythrocytes of healthy humans and humans with PAH respond to UT-15C with increases in cAMP levels and ATP release. In both groups, UT-15C-induced ATP release was potentiated by zaprinast and tadalafil. The effect of tadalafil was prevented by pre-treatment with an inhibitor of soluble guanylyl cyclase in healthy human erythrocytes. Importantly, UT-15C-induced ATP release was greater in PAH erythrocytes than in healthy human erythrocytes in both the presence and the absence of PDE5 inhibitors. The finding that prostacyclin analogs and PDE5 inhibitors work synergistically to enhance release of the potent vasodilator ATP from PAH erythrocytes provides a new rationale for the co-administration of these drugs in this disease. Moreover, these results suggest that the erythrocyte is a novel target for future drug development for the treatment of PAH.

  8. Pulmonary arterial hypertension and cor pulmonale associated with chronic domestic woodsmoke inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Sandoval, J.; Salas, J.; Martinez-Guerra, M.L.; Gomez, A.; Martinez, C.; Portales, A.; Palomar, A.; Villegas, M.; Barrios, R. (Instituto Nacional de Cardiologia, Ignacio Chavez, Mexico City (Mexico))

    1993-01-01

    We describe the clinical, radiologic, functional, and pulmonary hemodynamic characteristics of a group of 30 nonsmoking patients with a lung disease that may be related to intense, long-standing indoor wood-smoke exposure. The endoscopic and some of the pathologic findings are also presented. Intense and prolonged wood-smoke inhalation may produce a chronic pulmonary disease that is similar in many aspects to other forms of inorganic dust-exposure interstitial lung disease. It affects mostly country women in their 60s, and severe dyspnea and cough are the outstanding complaints. The chest roentgenograms show a diffuse, bilateral, reticulonodular pattern, combined with normalized or hyperinflated lungs, as well as indirect signs of pulmonary arterial hypertension (PAH). On the pulmonary function test the patients show a mixed restrictive-obstructive pattern with severe hypoxemia and variable degrees of hypercapnia. Endoscopic findings are those of acute and chronic bronchitis and intense anthracotic staining of the airways appears to be quite characteristic. Fibrous and inflammatory focal thickening of the alveolar septa as well as diffuse parenchymal anthracotic deposits are the most prominent pathologic findings, although inflammatory changes of the bronchial epithelium are also present. The patients had severe PAH in which, as in other chronic lung diseases, chronic alveolar hypoxia may play the main pathogenetic role. However, PAH in wood-smoke inhalation-associated lung disease (WSIALD) appears to be more severe than in other forms of interstitial lung disease and tobacco-related COPD. The patients we studied are a selected group and they may represent one end of the spectrum of the WSIALD.

  9. Electrical carotid sinus stimulation in treatment resistant arterial hypertension.

    Science.gov (United States)

    Jordan, Jens; Heusser, Karsten; Brinkmann, Julia; Tank, Jens

    2012-12-24

    Treatment resistant arterial hypertension is commonly defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. The sympathetic nervous system promotes arterial hypertension and cardiovascular as well as renal damage, thus, providing a logical treatment target in these patients. Recent physiological studies suggest that baroreflex mechanisms contribute to long-term control of sympathetic activity and blood pressure providing an impetus for the development of electrical carotid sinus stimulators. The concept behind electrical stimulation of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by the brain as blood pressure increase. Then, baroreflex efferent structures are adjusted to counteract the perceived blood pressure increase. Electrical stimulators directly activating afferent baroreflex nerves were developed years earlier but failed for technical reasons. Recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall. Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation. Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension. Clinical studies suggest that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering blood pressure. Yet, not all patients respond to treatment. Additional clinical trials are required. Patients equipped with an electrical carotid sinus stimulator provide a unique opportunity gaining insight in human baroreflex physiology.

  10. Pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction in dogs.

    Science.gov (United States)

    Stepien, Rebecca L

    2009-09-01

    Pulmonary arterial hypertension is a description of a physiological finding rather than a diagnosis. Pulmonary arterial pressure is the result of interactions among pulmonary blood flow (right ventricular cardiac output), pulmonary vascular impedance and post-capillary pressure (typically reflecting left atrial pressure). When elevations in pulmonary arterial pressure (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at rest) are accompanied by increased left atrial pressure, pulmonary arterial hypertension may be considered secondary to left-heart failure. Introduction of Doppler methods to diagnose pulmonary arterial hypertension has increased the awareness of the prevalence and importance of pulmonary arterial hypertension dogs with left-heart failure. Increasing understanding of the mechanism of development of pulmonary venous hypertension and reactive pulmonary arterial hypertension in dogs with left-heart disease has led to the development of successful additive therapies for progressive clinical signs in the setting of chronic therapy for congestive heart failure due to left-sided valvular and myocardial dysfunction. Because effective therapies for pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction are now available, screening for pulmonary arterial hypertension should be a regular part of the Doppler echocardiographic examination in a clinical setting of chronic therapy for left-sided congestive heart failure due to valvular or myocardial disease.

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    Karoli N.A.

    2013-06-01

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

  13. 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

  14. Arterial hypertension and cardiovascular risk in HIV-infected patients.

    Science.gov (United States)

    Calò, Lorenzo A; Caielli, Paola; Maiolino, Giuseppe; Rossi, Gianpaolo

    2013-08-01

    The dramatic change of the natural history of HIV-infected patients by highly active antiretroviral therapy (HAART) has exposed these patients to cardiovascular risk, including cardiovascular disease and hypertension. In HIV-infected patients, the development of arterial hypertension, at least in the medium-long term is an established feature, although recognized predictors of its development have not been clearly identified. In addition, conflicting data regarding the influence of antiretroviral therapy (ART) are reported. The presence of a proinflammatory state and oxidative stress-mediated endothelial dysfunction seem, however, to play a pathophysiologic role. In this review, we examine and provide a comprehensive, literature based, consideration of the pathophysiologic aspects of hypertension in these patients. HIV-infected patients, independently of the presence of hypertension, remain at very high cardiovascular risk due to the presence of the same cardiovascular risk factors recognized for the general population with, in addition, the indirect influence of the ART, essentially via its effect on lipid metabolism. This review based on the evidence from the literature, concludes that the management of HIV-infected patients in terms of cardiovascular prevention emerges as a priority. The consideration of cardiovascular risk in these patients should receive the same emphasis given for the general population at high cardiovascular risk, including adequate blood pressure control according to international guidelines.

  15. COMPARATIVE MORPHOFUNCTIONAL CHARACTERISTIC OF ADRENAL GLANDS IN ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    S. Yu. Alyabyeva

    2015-01-01

    Full Text Available The article is devoted to the study of morphological changes of the adrenal glands in arterial hyperten-sion. Adrenals investigated persons who do not suffer in life and suffering from hypertension during the life of hypertension and died from various causes – is incompatible with the life of a mechanical trauma, cerebral hemorrhage, and acute left ventricular failure. In each case, each of the adrenal glands were assessed: the presence and severity of focal and diffuse mononuclear infiltration, the number of lympho-cytes, monocytes, plasma cells and fibroblasts arranged in the respective zones of the cortex and medulla, the severity of hyperemia and edema of various structural parts, the number of zones cortex and medulla endocrinocytes with pycnotic nuclei in the reticular zone evaluated the distribution of secretory cells with lipofuscin and the degree of saturation of the cytoplasm of the secretory cells, in secretory cells of medul-la evaluated nuclear-cytoplasmic ratio, the severity of vacuolization and basophils cytoplasm revealed a number of regularities of morphological changes depending from the various clinical manifestations of hypertension, defining the ultimate option of dying. At the heart tanatogenesis version are more pro-nounced morphological features hyperfunctions glomerular zone – namely delipidization left and right glands. The beam and netted areas contralateral glands embodiment of dying of a heart compared to the brain, is more pronounced hyperemia. When cardiac variant tanatogenesis more pronounced focal lym-phoid infiltration and vacuolization in secretory cells of left adrenal medulla.

  16. Arterial stiffening provides sufficient explanation for primary hypertension.

    Directory of Open Access Journals (Sweden)

    Klas H Pettersen

    2014-05-01

    Full Text Available Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension. Specifically, the empirically observed chronic changes in pulse pressure with age and the impaired capacity of hypertensive individuals to regulate short-term changes in blood pressure arise as emergent properties of the integrated system. The results are consistent with available experimental data from chemical and surgical manipulation of the cardio-vascular system. In contrast to widely held opinions, the results suggest that primary hypertension can be attributed to a mechanogenic etiology without challenging current conceptions of renal and sympathetic nervous system function.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  18. Medial defects of the small pulmonary arteries in fatal pulmonary hypertension in infants with trisomy 13 and trisomy 18.

    Science.gov (United States)

    Tahara, Masahiro; Shimozono, Saiko; Nitta, Tetsuya; Yamaki, Shigeo

    2014-02-01

    Congestive heart failure is a major cause of early death in patients with trisomy 13 or 18 and congenital heart disease (CHD). Pulmonary artery banding for these patients early in life is preferred to protect the lungs from high pulmonary flow rates and improve survival. We performed open lung biopsies in 11 patients with trisomy 13 or 18 accompanied by CHD and severe pulmonary artery hypertension (PAH) between 2009 and 2011. Two (18.2%) of these 11 patients had medial defects of the small pulmonary arteries. One patient with trisomy 13 and an atrial septal defect developed lung hemorrhage and lung edema at the age of 9 months and died at the age of 13 months. The lumens of the small pulmonary arteries of the other patient with trisomy 18 and a ventricular septal defect became occluded due to the intimal proliferation of fibrous tissues at the age of 2 months. This patient died at the age of 27 months. The deaths of both patients were associated with heart-related factors. Patients with medial defects are vulnerable to intimal proliferation in the small pulmonary arteries. More patients with trisomy 13 or 18 and CHD might have similar pulmonary vascular changes. The small pulmonary arteries of patients with trisomy 13 and 18 should be further analyzed.

  19. Tadalafil Therapy for Pulmonary Arterial Hypertension%他达那非治疗肺动脉高压进展

    Institute of Scientific and Technical Information of China (English)

    温亮; 刘倩倩; 杨庆辉; 韦世鹏; 白晓鹏; 钟丽华; 陈延军

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that is characterized by small pulmonary vascular remodeling and elevation of pulmonary vascular resistance, leading right heart failure and death. Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway. PHIRST trial concluded that tadalafil 40 mg improved 6 minutes walk distance and reduced clinical worsening in patients with pulmonary arterial hypertension. This article reviews tadalafil therapy for pulmonary arterial hypertension.%肺动脉高压是一类以小肺动脉血管重构为特征的恶性肺血管疾病,肺血管阻力进行性升高最终导致右心衰竭死亡.肺动脉高压的药物治疗主要针对前列环素、内皮素、一氧化氮三个靶点.他达那非(Tadalafil)是一种口服、长效、选择性5-型磷酸二酯酶抑制剂,增加环磷酸鸟苷(cGMP)浓度,通过一氧化氮途径起到治疗作用.PHIRST临床试验证实肺动脉高压患者每日一次口服他达那非40mg,能够提高6分钟步行距离,减少临床恶化.本文就他达那非治疗肺动脉高压研究新进展作一综述.

  20. A loud right-apical systolic murmur is associated with the diagnosis of secondary pulmonary arterial hypertension: retrospective analysis of data from 201 consecutive client-owned dogs (2006-2007).

    Science.gov (United States)

    Ohad, D G; Lenchner, I; Bdolah-Abram, T; Segev, G

    2013-12-01

    Canine pulmonary arterial hypertension (PAH) remains under-recognized and under-treated despite being prevalent. This retrospective study investigated whether selected historical and physical examination findings were associated with the diagnosis of canine PAH, defined as tricuspid regurgitation (TR) with a confirmed systolic pressure gradient ≥ 35 mm Hg. Two hundred and one client-owned dogs (PAH group, n=96; control group, n=105) were studied. Dogs in the control group had TR with a confirmed systolic gradient dogs underwent a complete physical examination and a complete echocardiographic assessment. A loud systolic right-apical murmur (RAM) was significantly associated with TR ≥ 35 mm Hg. The proportion of dogs with PAH significantly increased as the RAM grade increased, with odds ratios of 4.4-37.6 for Grades 3/6-5/6 (P=0.004 to dogs with degenerative valve disease is highly suggestive of concurrent PAH.

  1. Safety experience with bosentan in 146 children 2-11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program

    DEFF Research Database (Denmark)

    Beghetti, M.; Hoeper, M.M.; Kiely, D.G.;

    2008-01-01

    The oral dual endothelin receptor antagonist bosentan has been shown to improve the short- and medium-term course of adult pulmonary arterial hypertension (PAH); however, data from clinical studies in children are limited. This analysis investigated the safety profile of bosentan in pediatric...... patients in a European, prospective, noninterventional, Internet-based postmarketing surveillance database (Tracleer PMS). Pediatric patients (aged 2-11 y) were compared with patients aged > or =12 y. Over a 30-mo period, 4994 patients, including 146 bosentan-naive pediatric patients (51.4% males), were...... captured in the database. Predominant etiologies in children were idiopathic PAH (40.4%) and PAH related to congenital heart disease (45.2%). The majority of children were in New York Heart Association functional class II (28.1%) or III (50.7%), and median exposure to bosentan was 29.1 wk. Elevated...

  2. 肺动脉高压治疗的最新进展%Recent progress of the treatment for pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    俞砚喆; 解卫平

    2011-01-01

    Pulmonary arterial hypertension ( PAH ) is a severe clinical syndrome, which is characterized by the pesistant elevated pulmonary artery pressure with various causes. Without the appropriate treatment,it will lead to pulmonary vascular remodeling, and ultimately the development of right heart failure, therefore it is widely regarded as a desease of poor prognosis. However, the early diagnosis and effective treatment can improve the survival rate as well as the quality of life in PAH patients. Recently,the deepening understanding of the pathogenesis of PAH promotes the development of treatment for PAH. The recent progress of the treatment for PAH will be reviewed as follows.%肺动脉高压是各种原因引起的肺动脉压力持续升高的临床综合征.若缺乏相应的治疗,将导致肺血管重塑,最终发展为右心衰竭,预后极差.但早期诊断及合理治疗可提高该病患者的生存率并改善患者的生存质量.近年,对肺动脉高压发病机制认识的不断深入推动了肺动脉高压治疗手段的发展,现将肺动脉高压治疗的最新进展综述如下.

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

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    Serra Walter

    2010-07-01

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

  4. Current practices in the use of sildenafil for pulmonary arterial hypertension in Brazilian hospitals

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    Cabral Lucio M

    2009-03-01

    Full Text Available Abstract Background Sildenafil is a cyclic guanosine monophosphate-specific phosphodiesterase-5 inhibitor used for treating pulmonary hypertension. Although the use of sildenafil in patients under 18 years old is off-label, this inhibitor has been widely prescribed for children treatment at hospitals in Brazil. In this work we evaluated the current practices in using sildenafil in the three main reference hospitals of Rio de Janeiro to design a clinical trial. Then we analyzed the content of sildenafil in powder paper preparations used in these institutions. Methods and Results We assessed the data about the use of sildenafil in three reference hospitals including Instituto Nacional de Cardiologia – INC, Instituto Estadual de Cardiologia Aloysio de Castro – IECAC and Hospital Pro-Cardíaco – HPC. The pharmacy records were analyzed from April 1st, 2008 to April 30th, 2008 and interviews with the pharmacists were also performed. Our results showed that INC used the greatest amount of sildenafil in: treatment of pulmonary arterial hypertension (PAH, management of transient PAH during surgery, preparation for cardiac transplantation and haemodynamic studies during cardiac catheterization. Meanwhile IECAC and HPC used sildenafil only for treating PAH in few patients during the period evaluated. In INC and IECAC, sildenafil was available in tablets, and powder papers prepared by two private pharmacies and one public hospital pharmacy. In contrast all patients of HPC received sildenafil in tablets with no external manipulation. Our quantification analysis results using reverse-phase high performance liquid chromatography method showed that powder papers prepared by the private pharmacies from the sildenafil tablets presented only 58.5 to 89.3% of the declared concentration in contrast to samples from the public hospital pharmacy (104.4 to 105.3%. Conclusion Few patients received the prescribed sildenafil dose at the reference hospitals evaluated

  5. Correlation between JAK2 allele burden and pulmonary arterial hypertension and hematological parameters in Philadelphia negative JAK2 positive myeloproliferative neoplasms. An Egyptian experience.

    Science.gov (United States)

    Mattar, Mervat M; Morad, Mohammed Abdel Kader; El Husseiny, Noha M; Ali, Noha H; El Demerdash, Doaa M

    2016-10-01

    Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial. The aim of this study is to screen Egyptian Philadelphia negative JAK2 positive myeloproliferative neoplasm patients for the presence of PAH and its correlation with JAK2 allele burden. We also made a review for correlation of JAK2 allele with hematological parameters comparing our results to others. We enrolled 60 patients with Philadelphia negative myeloproliferative neoplasms. All patients enrolled in the study were subjected to laboratory and imaging workup in the form of CBC, liver, kidney profile, bone marrow examination, abdominal ultrasonography, and transthoracic echocardiography. Our results revealed that 7 patients out of 60 (11.67 %) had pulmonary arterial hypertension, 3 patients with PMF, 2 patients with PRV, and 2 patients with ET, and its correlation with JAK2 allele burden was not statistically significant. Correlation analysis between JAK2 V617F allele burden and other parameters revealed: statistical significant correlation with age, HB, HCT, PLT, UA, LDH, and splenic diameter but insignificant correlation with WBCs and PAH. Pulmonary arterial hypertension prevalence in our study was 11.67 % and no significant correlation with JAK 2 allele burden. Our study is the largest one up to our knowledge that studies the association between its prevalence and JAK2 burden.

  6. Pulmonary arterial hypertension in congenital cardiac disease - the need for refinement of the Evian-Venice classification

    NARCIS (Netherlands)

    van Albada, Mirjam E.; Berger, Rolf M. F.

    2008-01-01

    Pulmonary hypertension associated with congenital systemic-to-pulmonary shunts has been classified, in the Evian-Venice classification, as Pulmonary Arterial Hypertension, which includes a heterogeneous group of conditions. Emerging options for treatment of patients with pulmonary arterial hypertens

  7. [Characteristics of arterial hypertension in psychoemotional burnout of emergency medical staffers].

    Science.gov (United States)

    Komissarova, E M; Ermakova, M A

    2011-01-01

    Medical profession requires not only skills, but also significant emotional dedication that leads to psychoemotional overstrain and frequently to emotional burnout influencing blood pressure level, cardiovascular state and arterial hypertension course. With this, studying influence of psycho-social factors in medical staffers' occupational life, in accordance with length of service, on cardiovascular system with arterial hypertension is topical.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  9. Ambulatory arterial stiffness indices and target organ damage in hypertension

    Directory of Open Access Journals (Sweden)

    Gómez-Marcos Manuel

    2012-01-01

    Full Text Available Abstract Background The present study was designed to evaluate which arterial stiffness parameter - AASI or the home arterial stiffness index (HASI - correlates best with vascular, cardiac and renal damage in hypertensive individuals. Methods A cross-sectional study was carried out involving 258 hypertensive patients. AASI and HASI were defined as the 1-regression slope of diastolic over systolic blood pressure readings obtained from 24-hour recordings and home blood pressure over 6 days. Renal damage was evaluated by glomerular filtration rate (GFR and microalbuminuria; vascular damage by carotid intima-media thickness (IMT, pulse wave velocity (PWV and ankle/brachial index (ABI; and left ventricular hypertrophy by the Cornell voltage-duration product (VDP and the Novacode index. Results AASI and HASI were not correlated with microalbuminuria, however AASI and HASI- blood pressure variability ratio (BPVR showed negative correlation with GRF. The Cornell PDV was positively correlated with AASI- BPVR-Sleep (r = 0.15, p Conclusions After adjusting for age, gender and 24-hour heart, the variables that best associated with the variability of IMT, PWV and ABI were AASI and Awake-AASI, and with GFR was HASI-BPVR.

  10. Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Swiston John R

    2010-01-01

    Full Text Available Abstract Background Previous meta-analyses of treatments for pulmonary arterial hypertension (PAH have not shown mortality benefit from any individual class of medication. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group. Results 1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs, and phosphodiesterase type 5 (PDE5 inhibitors. Pooled relative risks (RRs and 95% confidence intervals (CIs were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82, particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63. Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60 or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08. All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment. Conclusions Treatment of PAH with prostanoids

  11. Assessment of measurement properties of peak VO2 in children with pulmonary arterial hypertension

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    Cappelleri Joseph C

    2012-09-01

    Full Text Available Abstract Background The 6-minute walk test evaluates the effect of pharmacologic intervention in adults with pulmonary arterial hypertension (PAH but, for reasons of compliance or reliability, may not be appropriate for children at all ages. Thus, peak oxygen consumption (VO2, maximal exercise test was used instead in a pediatric PAH trial (STARTS-1 to evaluate pharmacologic intervention with sildenafil. This was the first large placebo-controlled trial to use the peak VO2 endpoint in this population. Our working hypothesis was that, as with other populations, percentage changes in peak VO2 in pediatric patients with PAH are reliable and are associated with changes in other clinical endpoints. Methods Using data from the subpopulation of 106 patients who were developmentally and physically able to perform exercise testing, all of whom were World Health Organization Functional Class (WHO FC I, II, or III, reliability was assessed using the intraclass correlation coefficient and Bland-Altman plot on screening and baseline data. Relationships between percentage change in peak VO2 from baseline to end of treatment and other endpoints were evaluated using correlation coefficients and regression analyses. Results The intraclass correlation was 0.79 between screening and baseline peak VO2, an agreement that was supported by the Bland-Altman plot. Percentage change in peak VO2 correlated well (r ≥0.40 and showed responsiveness to a physician global assessment of change and with change in WHO FC (for baseline classes I and III. Percentage change in peak VO2 did not correlate with change in the Family Cohesion of the Child Health Questionnaire (r = 0.04 or with a subject global assessment of change (r = 0.12. The latter may have been influenced by child and parental-proxy response and instrument administration. Conclusion In pediatric PAH patients who are developmentally and physically able to perform exercise testing, peak VO2 measurements

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

    Science.gov (United States)

    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.

  13. Nuclear Factor κ-B Is Activated in the Pulmonary Vessels of Patients with End-Stage Idiopathic Pulmonary Arterial Hypertension

    Science.gov (United States)

    Price, Laura C.; Caramori, Gaetano; Perros, Frederic; Meng, Chao; Gambaryan, Natalia; Dorfmuller, Peter; Montani, David; Casolari, Paolo; Zhu, Jie; Dimopoulos, Konstantinos; Shao, Dongmin; Girerd, Barbara; Mumby, Sharon; Proudfoot, Alastair; Griffiths, Mark; Papi, Alberto; Humbert, Marc; Adcock, Ian M.; Wort, S. John

    2013-01-01

    Objectives To assess activation of the inflammatory transcription factor NF-kappa B (NF-κB) in human idiopathic pulmonary arterial hypertension (PAH). Background Idiopathic PAH is a severe progressive disease characterized by pulmonary vascular remodeling and excessive proliferation of vascular cells. Increasing evidence indicates that inflammation is important in disease pathophysiology. Methods NF-κB-p65 and CD68, CD20 and CD45 were measured by immunohistochemistry and confocal microscopy on lung specimens from patients with idiopathic PAH (n = 12) and controls undergoing lung surgery (n = 14). Clinical data were recorded for all patients including invasive pulmonary hemodynamics for the PAH patients. Immunohistochemical images were analyzed by blinded observers to include standard pulmonary vascular morphometry; absolute macrophage counts/mm2 and p65-positivity (p65+) using composite images and image-analysis software; and cytoplasmic:nuclear p65+ of individual pulmonary arterial endothelial and smooth muscle cells (PASMC) in 10–20 pulmonary arteries or arterioles per subject. The expression of ET-1 and CCL5 (RANTES) in whole lung was determined by RT-qPCR. Results Macrophage numbers were increased in idiopathic PAH versus controls (49.0±4.5 vs. 7.95±1.9 macrophages/100 mm2, p<0.0001): these macrophages demonstrated more nuclear p65+ than in macrophages from controls (16.9±2.49 vs. 3.5±1.25%, p<0.001). An increase in p65+ was also seen in perivascular lymphocytes in patients with PAH. Furthermore, NF-κB activation was increased in pulmonary arterial endothelial cells (62.3±2.9 vs. 14.4±3.8, p<0.0001) and PASMC (22.6±2.3 vs. 11.2±2.0, p<0.001) in patients with PAH versus controls, with similar findings in arterioles. Gene expression of both ET-1 mRNA ((0.213±0.069 vs. 1.06±0.23, p<0.01) and CCL5 (RANTES) (0.16±0.045 vs. 0.26±0.039, p<0.05) was increased in whole lung homogenates from patients with PAH. Conclusions NF-κB is activated in

  14. 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

  15. 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.

  16. Effect of Feikangning composition in improving the pulmonary function in patients with COPD merged with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Li-Yun Wang

    2016-01-01

    Objective:To explore the effect of Feikangning composition in improving the pulmonary function in patients with COPD merged with pulmonary arterial hypertension (PAH), and observe the changes of ET-1 and D-D levels before and after treatment.Methods:A total of 52 patients with COPD merged with PAH who were admitted in our hospital were included in the study and randomized into the treatment group (n=31) and the control group (n=21). The patients in the two groups were given routine treatments after admission. On this basis, the patients in the treatment group were given Feikangning composition. ET-1 and D-D levels before treatment and 1 month after treatment in the two groups were detected. FEV1, FVC, FEV1%, mPAP, TPR, and SteO2 before and after treatment in the two groups were compared. Results:FEV1, FVC, and FEV1% after treatment in the treatment group were significantly higher than those in the control group. PAP and SteO2 after treatment in the treatment group were significantly higher than those in the control group, while TPR was significantly lower than that in the control group. ET-1 and D-D levels after treatment in the treatment group were significantly lower than those in the control group.Conclusions: Feikangning composition can effectively improve the ventilation function in patients with COPD merged with PAH, and regulate the endothelin balance, with a significant efficacy.

  17. 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.

  18. The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension.

    Science.gov (United States)

    Kherbeck, Nada; Tamby, Mathieu C; Bussone, Guillaume; Dib, Hanadi; Perros, Frederic; Humbert, Marc; Mouthon, Luc

    2013-02-01

    Pulmonary arterial hypertension is characterized by a remodeling of pulmonary arteries with endothelial cell, fibroblast, and vascular smooth muscle cell activation and proliferation. Since pulmonary arterial hypertension occurs frequently in autoimmune conditions such as systemic sclerosis, inflammation and autoimmunity have been suspected to play a critical role in both idiopathic pulmonary arterial hypertension and systemic sclerosis-associated pulmonary arterial hypertension. High levels of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, platelet-derived growth factor, or macrophage inflammatory protein 1 have been found in lung samples of patients with pulmonary arterial hypertension, along with inflammatory cell infiltrates mainly composed of macrophages and dendritic cells, T and B lymphocytes. In addition, circulating autoantibodies are found in the peripheral blood of patients. Thus, autoimmunity and inflammation probably play a role in the development of pulmonary arterial hypertension. In this setting, it would be important to set-up new experimental models of pulmonary arterial hypertension, in order to define novel therapeutics that specifically target immune disturbances in this devastating condition.

  19. 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 PAH

  20. 2009 ESC/ERS Pulmonary Hypertension Guidelines and Connective Tissue Disease

    OpenAIRE

    Norifumi Nakanishi

    2011-01-01

    Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25 mmHg at the 4th World Symposium on Pulmonary Hypertension. In 2009, the European Society of Cardiology and European Respiratory Society jointly created guidelines for practical pulmonary hypertension classifications and treatments based on the discussions at the 4th World Symposium. This classification is characterized by division into five groups: Pulmonary arterial hypertension (PAH); Pulmonary hypertension due to left...

  1. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension.

    Science.gov (United States)

    Yang, Zhen; Chen, Long; Su, Chen; Xia, Wen-Hao; Wang, Yan; Wang, Jie-Mei; Chen, Fei; Zhang, Yuan-Yuan; Wu, Fang; Xu, Shi-Yue; Zhang, Xiao-Lin; Tao, Jun

    2010-01-01

    Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury.

  2. [Ultrastructure of the intima of human pial arteries in arterial hypertension].

    Science.gov (United States)

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Ultrastructure of the intima of human pial arteries obtained from 5 male cadavers of practically healthy individuals and from 8 cadavers of the patients with the intravitally diagnosed grade I arterial hypertension (AH) was studied by scanning and transmission electron microscopy. AH was found to be associated with the remodeling of the intimal structural elements in the pial arteries. In most arteries, the changes were detected in the microrelief of the luminal surface and in the permeability of the vascular endothelial lining and of the subendothelial layer. During this remodeling, some endothelial cells were found in the state of structural and functional adaptation to the elevated arterial pressure, while the others were undergoing the dystrophic changes. The latter include the cells containing lipid inclusions, as well as the endothelial cells presumably in the state of apoptosis. The destruction of the intercellular junctions, the disturbances in the endothelium permeability contributed to the development of subendothelial layer edema, resulting in its significant thickening. This layer became looser and contained abundant collagen fibrils.

  3. Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Smidt, U M

    1983-01-01

    in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.......Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive...... method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase...

  4. microRNA在肺动脉高压形成中的作用%Roles of microRNA in pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    赵施皓; 杨智伟; 郑煦暘; 冯娜; 李娟; 裴建明

    2013-01-01

    MicroRNAs are endogenously expressed and highly conserved noncoding RNAs that regulate gene expressions in eukaryons.Recent studies have found that dysregulation of some microRNAs plays an important role in pulmonary arterial hypertension (PAH) and other cardiovascular diseases.MicroRNAs thus become novel biomarkers of these diseases and show potentials for clinical applications.This review focuses on the roles of microRNAs in PAH.%微小RNA (microRNA)是真核细胞内源性表达、高度保守、长度约为22个核苷酸的非编码RNA,可以调控基因的表达,与众多疾病的发生发展有关.近期研究发现,多种microRNAs表达失调在肺动脉高压(pulmonary arterial hypertension,PAH)及多种心血管疾病的发展中起重要作用,其成为新的分子生物学标志并有广泛的治疗应用前景.本文就microRNA在PAH中的作用作一综述.

  5. Relationships between use of statins and arterial stiffness in normotensive and hypertensive patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-guang; CHEN Bing-wei; L(U) Na-qiang; CHENG Yan-mei; DANG Ai-min

    2013-01-01

    Background Statins improve arterial stiffness in patients with coronary artery disease (CAD).Hypertension is a predominant contributor of arterial stiffening.However,the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated.Therefore,in this study,we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients.Methods Brachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients,including 220 hypertensive CAD patients (121 used statins,99 did not) and 217 normotensive CAD patients (105 used statins,112 did not).The normotensive and hypertensive CAD patients were matched according to age,sex,and body mass index (BMI).Results In the normotensive and hypertensive CAD patients,lipid profiles were significantly improved in the statin group compared with the non-statin group.No significant differences in the administered statins (i.e.,atorvastatin,simvastatin,rosuvastatin,and pravastatin) and statin therapy duration were found between normotensive and hypertensive CAD patients (all P>0.05).No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients,normotensive CAD patients,or hypertensive CAD patients (all P>0.05).ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients ((1331.68±167.52) cm/s vs.(1468.61±244.54) cm/s,P=0.002) but not in hypertensive CAD patients (P>0.05).In multiple linear regression analyses,statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P=0.018) but not in hypertensive CAD patients (P>0.05).Conclusions Statins may significantly improve arterial stiffness in CAD patients,and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population.Further studies are required to

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

    Science.gov (United States)

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

    2012-12-01

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

  7. [Successful pregnancy in a patient with idiopathic pulmonary arterial hypertension. Case report].

    Science.gov (United States)

    Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János

    2016-04-10

    Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.

  8. [Etiology of endocrine arterial hypertensions: about a series of cases].

    Science.gov (United States)

    Bouznad, Naima; El Mghari, Ghizlane; El Ansari, Nawal

    2016-01-01

    Arterial hypertensions (HTA) of endocrine origin are a rare cause of hypertension; HTA overall prevalence don't exceed 4% of hypertensive patients. Research interest in endocrine HTA is due to the severity of some life-threatening, potentially curable and reversible forms of HTA. The aim of our study was to determine the clinical, paraclinical, etiological and therapeutic profile of secondary HTA of endocrine origin in patients treated in endocrinology department at the University Hospital Mohamed VI in Marrakech. We conducted a prospective, descriptive study spanned 4 years, enrolling 45 patients with endocrine HTA. The average age was 44.89 years, with a clear predominance of women (sex ratio 0.49). Etiology of endocrine HTA was dominated by pheochromocytoma (17 cases), hypercorticism (11 cases) and acromegaly (8 cases). HTA were paroxysmal in 24.4%. HTA were immediately classified as grade 3 severe in 40% of cases. HTA were complicated by heart disease in 24% of cases and by renal disease in 20% of cases. Curative treatment cleared up HTA in 60% of cases (27 cases). The diagnosis of secondary endocrine HTA is sometimes difficult because of the lack of clinical specificity. It is not unusual for HTA to be the only manifestation of the disease. In our study we noted the paroxysmal and severe nature of HTA. The potentially curable nature of HTA in more than two thirds of cases, demostrates the importance of early diagnosis of each severe HTA resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

  9. Quantitative 3D pulmonary MR-perfusion in patients with pulmonary arterial hypertension: Correlation with invasive pressure measurements

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian [Department of Pediatric Radiology, Children' s Hospital University Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg (Germany) and Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)]. E-mail: ley@gmx.net; Mereles, Derliz [Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Risse, Frank [Medical Physics in Radiology (E020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Gruenig, Ekkehard [Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Ley-Zaporozhan, Julia [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Tecer, Zueleyha [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Puderbach, Michael [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Fink, Christian [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Clinical Radiology, University Medical Center Grosshadern, Ludwigs-Maximilians-University, Munich (Germany); Kauczor, Hans-Ulrich [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2007-02-15

    Purpose: Pathological changes of the peripheral pulmonary arteries induce pulmonary arterial hypertension (PAH). Aim of this study was to quantitatively assess the effect of PAH on pulmonary perfusion by 3D-MR-perfusion techniques and to compare findings to healthy controls. Furthermore, quantitative perfusion data were correlated with invasive pressure measurements. Material and methods: Five volunteers and 20 PAH patients (WHO class II or III) were examined using a 1.5 T MR scanner. Measurement of pulmonary perfusion was done in an inspiratory breathhold (FLASH3D; 3.5 mm x 1.9 mm x 4 mm; TA per 3D dataset 1.5 s). Injection of contrast media (0.1 mmol Gd-DTPA/kg BW) and image acquisition were started simultaneously. Evaluation of 3D perfusion was done using singular value decomposition. Lung borders were outlined manually. Each lung volume was divided into three regions (anterior, middle, posterior), and the following parameters were assessed: Time-to-Peak (TTP), blood flow (PBF), blood volume (PBV), and mean transit time (MTT). In 10 patients invasive pulmonary artery pressure measurements were available and correlated to the perfusion measurements. Results: In both, controls and patients, an anterior-to-posterior gradient with higher PBF and PBV posterior was observed. In the posterior lung region, a significant difference (p < 0.05) was found for TTP (12 s versus 16 s) and MTT (4 s versus 6 s) between volunteers and patients. PBF and PBV were lower in patients than in volunteers (i.e. dorsal regions: 124 versus 180 ml/100 ml/min and 10 versus 12 ml/100 ml), but the difference failed to be significant. The ratio of PBF and PBV between the posterior and the middle or ventral regions showed no difference between both groups. A moderate linear correlation between mean pulmonary arterial pressure (mPAP) and PBV (r = 0.51) and MTT (r = 0.56) was found. Conclusion: The only measurable effect of PAH on pulmonary perfusion is a prolonging of the MTT. There is only a

  10. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course

    Directory of Open Access Journals (Sweden)

    Baldi F

    2014-10-01

    Full Text Available Fabiana Baldi, Leonello Fuso, Eugenio Arrighi, Salvatore Valente Pulmonary Medicine Unit, Catholic University, Rome, Italy Abstract: Pulmonary arterial hypertension (PAH is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. Keywords: pulmonary hypertension, prognostic indicators, specific drug therapy, disease progression

  11. Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension.

    Science.gov (United States)

    Sivak, Joseph A; Raina, Amresh; Forfia, Paul R

    2016-09-01

    Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P right heart function in patients with PAH than in normal subjects.

  12. 妊娠合并肺动脉高压的管理及治疗%Management and Treatment for Pregnancy Complicated with Pulmonary Arterial Hypertension

    Institute of Scientific and Technical Information of China (English)

    曾汝园; 殷玲; 王以新; 冯妍; 李晓蕾

    2015-01-01

    妊娠合并肺动脉高压发病率低、预后差,近年来妊娠合并肺动脉高压患者的母婴结局有所改善,但母婴病死率仍然较高。肺动脉高压仍是妊娠禁忌证,而对于坚持继续妊娠的肺动脉高压患者,多学科专业团队协作的孕期管理、风险评估及孕期和产褥期治疗至关重要,可最大限度地改善母婴结局。本文就妊娠合并肺动脉高压的管理及治疗进行综述。%Pulmonary arterial hypertension( PAH) is a rare complication of pregnancy,but its prognosis is bad. In recent years,the mother-infant prognosis of pregnant women complicated with PAH is improved,but the mortality is still high, PAH is one of the contraindications of pregnancy. For pregnant women complicated with PAH, gestation management, risk assessment and treatment guided by multidisciplinary professional team collaboration is very important,which can furthest improve the mother-infant prognosis. This paper reviewed the management and treatment for pregnancy complicated with PAH.

  13. Current management approaches to portopulmonary hypertension.

    OpenAIRE

    2010-01-01

    Abstract Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with noncirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive hemodynamic co...

  14. Arterial hypertension and associated factors in patients submitted to myocardial revascularization

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Challenges in pulmonary hypertension: managing the unexpected

    OpenAIRE

    Olsson, Karen M; Massimiliano Palazzini

    2015-01-01

    The diverse challenges associated with diagnosis and management of patients with pulmonary hypertension are illustrated in this case-based review. Case 1 describes a patient diagnosed with pulmonary arterial hypertension (PAH) with right heart failure and active systemic lupus erythematosus who was effectively treated with an up-front triple combination of PAH therapies and immunosuppressive therapy. In case 2, a diagnosis of pulmonary veno-occlusive disease was reached after a combined appro...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Aldosterone Inactivates the Endothelin-B Receptor via a Cysteinyl Thiol Redox Switch to Decrease Pulmonary Endothelial Nitric Oxide Levels and Modulate Pulmonary Arterial Hypertension

    Science.gov (United States)

    Maron, Bradley A.; Zhang, Ying-Yi; White, Kevin; Chan, Stephen Y.; Handy, Diane E.; Mahoney, Christopher E.; Loscalzo, Joseph; Leopold, Jane A.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is characterized, in part, by decreased endothelial nitric oxide (NO•) production and elevated levels of endothelin-1. Endothelin-1 is known to stimulate endothelial nitric oxide synthase (eNOS) via the endothelin-B receptor (ETB), suggesting that this signaling pathway is perturbed in PAH. Endothelin-1 also stimulates adrenal aldosterone synthesis; in systemic blood vessels, hyperaldosteronism induces vascular dysfunction by increasing endothelial reactive oxygen species (ROS) generation and decreasing NO• levels. We hypothesized that aldosterone modulates PAH by disrupting ETB-eNOS signaling through a mechanism involving increased pulmonary endothelial oxidant stress. Methods and Results In rats with PAH, elevated endothelin-1 levels were associated with elevated aldosterone levels in plasma and lung tissue and decreased lung NO• metabolites in the absence of left heart failure. In human pulmonary artery endothelial cells (HPAECs), endothelin-1 increased aldosterone levels via PGC-1α/steroidogenesis factor-1-dependent upregulation of aldosterone synthase. Aldosterone also increased ROS production, which oxidatively modified cysteinyl thiols in the eNOS-activating region of ETB to decrease endothelin-1-stimulated eNOS activity. Substitution of ETB-Cys405 with alanine improved ETB-dependent NO• synthesis under conditions of oxidant stress, confirming that Cys405 is a redox sensitive thiol that is necessary for ETB-eNOS signaling. In HPAECs, mineralocorticoid receptor antagonism with spironolactone decreased aldosterone-mediated ROS generation and restored ETB-dependent NO• production. Spironolactone or eplerenone prevented or reversed pulmonary vascular remodeling and improved cardiopulmonary hemodynamics in two animal models of PAH in vivo. Conclusions Our findings demonstrate that aldosterone modulates an ETB cysteinyl thiol redox switch to decrease pulmonary endothelium-derived NO• and promote PAH

  19. The Different Expression of PPARγ in the Artery Tissues of Hypertensive Patients with Different Ages

    Institute of Scientific and Technical Information of China (English)

    Yongqin Li; Xiaolin Niu; Shijie Wang; Shaomin Li; Jiancang Ma

    2005-01-01

    Objective: To study the expression of the peroxisome proliferator-activated receptor γ(PPARγ) in the artery tissues of essential hypertensive patients, and the different changes with different ages, especially to the hypertensive patients more than 65 years old.Methods: Collected the mesenteric artery tissues of essential hypertensive patients( >65 years old group and <65 years old group)and patients with normal blood pressure,using immunohistochemical analysis and image acquiring and analysis system to detect the expression of PPARγ in the artery tissues. Results: the expression of PPARγ in the artery tissues of essential hypertensive patients is higher than that in the patients with normal blood pressure( P < 0.05), and to the group of hypertensive patients, the expression of PPARγ in > 65 years old group is higher than that in < 65 years old group ( P < 0.05). Conclusion: the expression of PPARγ in artery tissues is increased in hypertensive patients than in the patients with normal blood pressure, and increased with aging in hypertensive patients, suggesting that PPARγhas great relationship with hypertension.

  20. Is epistaxis associated with arterial hypertension? A systematic review of the literature.

    Science.gov (United States)

    Kikidis, D; Tsioufis, K; Papanikolaou, V; Zerva, K; Hantzakos, A

    2014-02-01

    Both epistaxis and hypertension are frequent problems in the adult population. The relationship between the level of arterial pressure and incidence of epistaxis in a patient with hypertension is a question that appears frequently in the clinical practice. A systematic review of the literature regarding the relation of arterial hypertension with epistaxis was performed through MEDLINE and EMBASE. All studies, whether examining the correlation of arterial pressure at presentation of a patient with nasal bleeding or the repercussion of episodes of epistaxis in hypertensive patients, were included in this review. Studies were evaluated independently by two reviewers according to a standard evaluation form. Overall, nine studies fulfilled our inclusion criteria. Five of them were single-group (patient) studies, while the remaining four included a control group. In eight studies, the patient group included patients with epistaxis, while one focused on hypertensive patients. Six out of nine studies agree that arterial pressure is higher at the time of epistaxis, as compared to the control group or to the general population. Seven out of nine studies conclude that there is cross-correlation between arterial pressure and the actual incident of epistaxis. The presence of high arterial blood pressure during the actual episode of nasal bleeding cannot establish a causative relationship with epistaxis, because of confounding stress and possible white coat phenomenon, but may lead to initial diagnosis of an already installed arterial hypertension.

  1. 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.

  2. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats.

    Science.gov (United States)

    Porvasnik, Stacy L; Germain, Sean; Embury, Jennifer; Gannon, Kimberley S; Jacques, Vincent; Murray, Justin; Byrne, Barry J; Shacham, Sharon; Al-Mousily, Faris

    2010-08-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease that results in right ventricular failure. 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. In the current study, the effects of PRX-08066 were assessed by using the monocrotaline (MCT)-induced PAH rat model. Male rats received 40 mg/kg MCT or phosphate-buffered saline and were treated orally twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks. Pulmonary and cardiac functions were evaluated by hemodynamics, heart weight, magnetic resonance imaging (MRI), pulmonary artery (PA) morphology, and histology. Cardiac MRI demonstrated that PRX-08066 (100 mg/kg) significantly (P PRX-08066 significantly reduced peak PA pressure at 50 and 100 mg/kg (P PRX-08066 therapy also significantly reduced right ventricle (RV)/body weight and RV/left ventricle + septum (P PRX-08066 (P PRX-08066 significantly attenuated the elevation in PA pressure and RV hypertrophy and maintained cardiac function. Pulmonary vascular remodeling was also diminished compared with MCT control rats. PRX-08066 prevents the severity of PAH in the MCT rat model.

  3. 肺动脉平滑肌细胞增殖相关因子与肺动脉高压%Relevant factors of pulmonary arterial smooth muscle cells proliferation and pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    张锋; 庞玉生; 劳金泉

    2016-01-01

    Pulmonary arterial hypertension (PAH)is a disease of unknown etiology that leads to a progressive increase in pulmonary vascular resistance (PVR),if untreated,ultimately right heart failure and high mortality.It is concerted pulmonary vascular contraction and vascular remodeling are the 2 main courses of physiology and pathology leading to PAH,especially the significant role of proliferation of pulmonary arterial smooth muscle cells.A lot of relevant factors are revealed to take a participation into regulating the proliferation of pulmonary arterial smooth muscle cells and finally PAH.%肺动脉高压是一不明原因导致的肺血管阻力不断增加的疾病,若未经治疗,最终导致右心衰竭和高病死率。肺血管收缩和血管重塑被认为是导致肺动脉高压的2个主要病理生理变化,特别是肺动脉平滑肌细胞的增殖起了重要的作用。研究表明许多相关因子参与肺动脉平滑肌细胞增殖的调控,从而导致肺动脉高压的发生。

  4. Congenital right pulmonary artery agenesis with atrial septal defect and pulmonary hypertension.

    Science.gov (United States)

    Orun, Utku Arman; Yilmaz, Osman; Bilici, Meki; Karademir, Selmin; Uner, Cigdem; Senocak, Filiz; Dogan, Vehbi

    2012-01-01

    Unilateral pulmonary artery agenesis is a rare congenital anomaly caused by a backward displacement of the conical artery of the truncus arteriosus. It is commonly associated with additional cardiovascular abnormalities. A 7-year-old girl was admitted to our clinic with the complaint of shortness of breath upon exertion. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery with atrial septal defect and pulmonary hypertension was demonstrated by echocardiography, computed tomography, and cardiac catheterization. Bosentan is effectively used to treat pulmonary arterial hypertension.

  5. [Treatment of compression of the left main coronary artery in patients with pulmonary hypertension].

    Science.gov (United States)

    Talavera, María L; Diez, Mirta; Cáneva, Jorge O; Boughen, Roberto P; Valdivieso, León; Mendiz, Oscar

    2011-01-01

    Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.

  6. Hypertriglyceridemic waist phenotype: a marker of cardiometabolic risk in patients with arterial hypertension

    OpenAIRE

    Ashcheulova, T.; Kovalyova, O.; Syed, M.

    2014-01-01

    Hypertriglyceridemic waist phenotype in patients with arterial hypertension was examined. Patients were categorized into 3 phenotype groups based on waist circumference means and plasma triglyceride levels: group 1 included patients (n=10) with normal waist circumference (

  7. Left-sided portal hypertension: Successful management by laparoscopic splenectomy following splenic artery embolization

    Directory of Open Access Journals (Sweden)

    Damiano Patrono

    2014-01-01

    CONCLUSION: Splenic artery embolization may be a valuable adjunct in case of left-sided portal hypertension requiring splenectomy, allowing a safe dissection of the splenic vessels even by laparoscopy.

  8. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

    Science.gov (United States)

    Courand, Pierre-Yves; Pina Jomir, Géraldine; Khouatra, Chahéra; Scheiber, Christian; Turquier, Ségolène; Glérant, Jean-Charles; Mastroianni, Bénédicte; Gentil, Béatrice; Blanchet-Legens, Anne-Sophie; Dib, Alfred; Derumeaux, Geneviève; Humbert, Marc; Mornex, Jean-François; Cordier, Jean-François; Cottin, Vincent

    2015-01-01

    Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF arterial hypertension.

  9. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels

    DEFF Research Database (Denmark)

    Chen, Xiaoping; Yang, Dachun; Ma, Shuangtao

    2010-01-01

    Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  11. Assessment of Pulmonary Arterial Hypertension by Intravascular Ultrasound%血管内超声在评估肺动脉高压中的应用

    Institute of Scientific and Technical Information of China (English)

    黄亿源

    2012-01-01

    Pulmonary arterial hypertension ( PAH) is a common clinical syndrome characterized by the remodeling of the small pulmonary arteries that results in a rise in the pulmonary arterial pressure and pulmonary vascular resistance. This eventually leads to right heart enlargement, right ventricular hypertrophy, right heart failure, and death. Currently, the main assessment of PAH is a histological biopsy, but its use has been limited because of the heterogeneity of pulmonary artery changes in PAH and the demand for the use of thoracotomy. In recent years, several studies on the use of intravascular ultrasound (IVUS) in evaluating the severity of pulmonary vascular damage in patients with PAH make it clear that IVUS could be effective in the assessment of PAH. This article reviews the assessment of pulmonary arteri-fal hypertension by IVUS, and its development.%肺动脉高压是由肺小动脉结构重建引起肺动脉压和肺血管阻力进行性增加,最终导致右心增大、右室壁肥厚、右心功能衰竭而死亡的疾病,是一组临床常见症候群.目前对肺动脉高压病情的主要评估方法是组织学活检,但由于肺动脉高压肺血管病变具有不均一性,且活检需要手术切开,所以使得肺组织活检在临床评价肺动脉高压病变方面受到限制.近年来有研究报道血管内超声可以评价肺动脉高压患者的肺血管损害程度.现就血管内超声在评估肺动脉高压的研究及发展趋势作一综述.

  12. 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

  13. Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

    Science.gov (United States)

    Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

    2016-01-01

    Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline.

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

    Science.gov (United States)

    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, Parterial elastance index at baseline was significantly higher in males, the magnitude of increase was steeper in females with the magnitude of change at 75 W of exercise 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.

  15. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

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    Yacoub Magdi H

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Borst Mathias M

    2009-12-01

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

  17. Relationship between resting heart rate and carotid artery structure in young hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    宋江宏

    2014-01-01

    Objective To investigate the relationship between resting heart rate(RHR)and carotid artery structure in young hypertensive patients.Methods A total of 663 primary hypertensive patients aged between 18 and 45(38.01±5.78)were chosen from the First Affiliated Hospital of Xinjing Medical University from January,2009 to January,2012.Patients under this study were

  18. Staging of hemodynamic parameters during development of experimental arterial hypertension in rabbits.

    Science.gov (United States)

    Frolov, V A; Blagonravov, M L; Zotov, A K; Zotova, T J

    2011-05-01

    The study analyzed changes in parameters of the central and intracardiac hemodynamics during the development of experimental arterial hypertension, which were assessed as the adaptive in nature. The development of hypertension demonstrated staging of the adaptive processes. The development of the adaptive responses was characterized by changes in the magnitude and probabilistic distribution of the hemodynamic parameters.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  20. Copper dependence of angioproliferation in pulmonary arterial hypertension in rats and humans.

    Science.gov (United States)

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

    2012-05-01

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

  1. Family history of hypertension and arterial elasticity characteristics in healthy young people.

    Science.gov (United States)

    Zhou, Lin; Chen, Yuanyuan; Sun, Ningling; Liu, Xirong

    2008-05-01

    Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP and an early change in arterial elasticity characteristics between young healthy individuals with or without a family history of hypertension and whether or not this increase is apparent in males as well as in females. A total of 270 normotensive healthy individuals (112 men and 158 women, aged 16 to 30 years) with or without a family history of hypertension, participated in conventional BP measurement and completed questionnaires covering basic information and a detailed family history of cardiovascular disease. Large arterial (capacitive) compliance (C1) and small arterial (oscillatory or reflective) compliance (C2) were derived from HDI/PulseWave CR-2000 (Hypertension Diagnostics, Minneapolis, USA). Based on family history information about parents and grandparents, three groups were formed: subjects with at least one hypertensive parent (group A), subjects with only hypertensive grandparents (group B), and subjects with normotensive parents and grandparents (group C). Men in group A had lower C1 and C2 along with higher systolic BP (SBP), diastolic BP (DBP), and heart rate than men in group C. Those in group B had intermediate C1, C2 and BP levels. C1 had a linear relationship with SBP, DBP, and heart rate. In the logistic regression model of family history of hypertension, C2 was lower in young normotensive males with parental hypertension (B = -0.315, exp B = 0.73, p = 0.03), independently of SBP, DBP, and heart rate. Among females, subjects with parental hypertension had higher systolic, mean arterial pressure, and pulse pressure (p young non-hypertensive subjects may be a risk factor for hypertension and may contribute to the progression to hypertension later in life.

  2. Anti-inflammatory and immunosuppressive agents in PAH.

    Science.gov (United States)

    Meloche, Jolyane; Renard, Sébastien; Provencher, Steeve; Bonnet, Sébastien

    2013-01-01

    Pulmonary arterial hypertension (PAH) pathobiology involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis, leading to enhanced pulmonary vascular resistance and pressure, to right heart failure and death. The exact mechanisms accounting for PAH development remain unknown, but growing evidence demonstrate that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Not surprisingly, PAH is often associated with diverse inflammatory disorders. Furthermore, pathologic specimens from PAH patients reveal an accumulation of inflammatory cells in and around vascular lesions, including macrophages, T and B cells, dendritic cells, and mast cells. Circulating levels of autoantibodies, chemokines, and cytokines are also increased in PAH patients and some of these correlate with disease severity and patients' outcome. Moreover, preclinical experiments demonstrated the key role of inflammation in PAH pathobiology. Immunosuppressive agents have also demonstrated beneficial effects in animal PAH models. In humans, observational studies suggested that immunosuppressive drugs may be effective in treating some PAH subtypes associated with marked inflammation. The present chapter reviews experimental and clinical evidence suggesting that inflammation is involved in the pathogenesis of PAH, as well the therapeutic potential of immunosuppressive agents in PAH.

  3. Digital capillaroscopy as important tool for early diagnostics of arterial hypertension

    Science.gov (United States)

    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.

  4. Expectation in targeted drug therapy for pulmonary arterial hypertension%肺动脉高压药物靶向治疗的展望

    Institute of Scientific and Technical Information of China (English)

    苏威; 李江

    2014-01-01

    肺动脉高压是一种以肺血管重构为特征,以肺血管阻力病理性增高为主要表现的临床综合征。肺动脉高压患者病情常呈进行性发展,最终导致右心衰竭和死亡。肺动脉高压现有的药物治疗在一定程度上改善了患者的症状,提高了生存率,但不能阻止病情的恶化,肺动脉高压患者的长期预后仍不尽人意。近年来,基于对肺动脉高压病理生理机制的深入认识,肺动脉高压的靶向治疗药物也不断涌现,为肺动脉高压的治疗带来了新的希望。现将肺动脉高压靶向治疗药物的研究进展进行综述。%Pulmonary arterial hypertension (PAH) is a vascular remodeling disease that pathologically increases pulmonary vascular resistance. Ultimately, PAH leads to right ventricular failure and premature death. Current therapeutic strategies modestly improve patients’ symptoms, pulmonary hemodynamic and survival. However, none of the current treatments is actually curative and long-term prognosis remains unsatisfactory. Recently, based on the advances in our understanding of PAH pathology, tremendous novel therapeutic targets were provided for treating PAH. This article reviewed recent progress in the therapeutic targeted drugs of pulmonary arterial hypertension.

  5. Role of microparticles in endothelial dysfunction and arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Thomas; Helbing; Christoph; Olivier; Christoph; Bode; Martin; Moser; Philipp; Diehl

    2014-01-01

    Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood surrogate markers for different pathological conditions, such as vascular inflammation, coagulation and tumour diseases. Several studies have investigated the abundance of microparticles of different cellular origins in multiple cardiovascular diseases. It thereby has been shown that microparticles released by platelets, leukocytes and endothelial cells can be found in conditions of endothelial dysfunction, acute and chronic vascular inflammation and hypercoagulation. In addition to their function as surrogate markers, several studies indicate that circulating microparticles can fuse with distinct target cells, such as endothelial cells or leukocyte, and thereby deliver cellular components of their parental cells to the target cells. Hence, microparticles are a novel entity of circulating, paracrine, biological vectors which can influence the phenotype, the function and presumably even the transcriptome of their target cells.This review article aims to give a brief overview about the microparticle biology with a focus on endothelial activation and arterial hypertension. More detailed information about the role of microparticles in pathophysiology and disease can be found in already published work.

  6. HEMODYNAMIC EFFECTS OF CARVEDILOL IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    L. I. Markova

    2006-01-01

    Full Text Available Aim. To evaluate the influence of carvedilol (Talliton, Egis, Hungary on daily profile of blood pressure (BP, anatomical and functional conditions of left ventricle (LV and cerebral circulation in patients with arterial hypertension (AH, stage II-III. Material and methods. 30 patients (10 men, 20 women, average age 51,9±7,9 y.o. with AH II-III stage ( RSSC,2004 and with initially affected daily profile of BP, cerebral circulation, anatomical and functional disorders of LV took carvedilol 25-75 mg/d during 6 months. Hemodynamics was estimated by ambulatory BP monitoring, Doppler Echocardiography, and ultrasound Dopplerography of extra cranial vessels. Results. A normalizing effect of carvedilol on abnormal daily profile of BP and cerebral circulation was determined. The treatment resulted in the regress of LV hypertrophy with predominant reduction of interventricular septum thickness and also the transformation of concentrical LV hypertrophy in excentrical one. Conclusion. Long-term therapy with carvedilol in patients with AH II-III stage provides a stable BP control and cardioprotective effect, improves cerebral circulation.

  7. 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 in u...

  8. Hemifacial spasm in a patient with basilar artery dolichoectasia caused by uncontrolled hypertension

    Directory of Open Access Journals (Sweden)

    Gordon S. Crabtree

    2016-10-01

    Full Text Available A 47-year-old male presented with a 2-year history of hemifacial spasm. Magnetic resonance imaging performed showed his tortuous basilar artery with nerve compression, and the patient was treated conservatively with botulinum toxin injections with complete resolution of symptoms. This rare disease was caused by his long history of hypertension, which led to his major basilar artery dolichoectasia.

  9. Successful accessory renal artery denervation in a patient with resistant hypertension

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    Halil Atas

    2014-01-01

    Full Text Available Renal sympathetic denervation is safe and effective in patients with resistant hypertension. In all of the studies of renal artery denervation, patients with accessory renal arteries are excluded. So there is not any data regarding renal sympathetic denervation applied to the accessory renal arteries. We present a young female patient with resistant hypertension despite use of five different antihypertensive drugs. The patient had a well developed (diameter >4 mm left renal accessory. We believe that if we omitted the well developed accessory renal artery, we would not have maintained adequate blood pressure control. Thus, we applied radiofrequency ablation to both renal arteries and left accessory artery. Immediately after the procedure, the patient′s blood pressure was reduced to 110/60 mmHg and this effect was continued during the first month of follow-up.

  10. Research advances of pathogenesis in pulmonary arterial hypertension related to connective tissue diseases%结缔组织病相关肺动脉高压发病机制研究进展

    Institute of Scientific and Technical Information of China (English)

    张明娜; 王秋月

    2012-01-01

    肺动脉高压(pulmonary arterial hypertension,PAH)是结缔组织病(connective tissue disease,CTD)常见且严重的并发症之一,影响CTD患者的预后,目前认为CTD相关PAH的发病机制可能是血管痉挛、血管壁重塑、肺间质病变、内皮损伤、血管活性物质失衡、免疫炎症机制、微血栓形成、基因多态性等多种原因,但具体发病机制尚不明确,本文对结缔组织病相关肺动脉高压( CTD-PAH)的发病机制研究作一综述.%Pulmonary arterial hypertension (PAH) as one of well-known and serious complications of various forms of connective tissue diseases (CTD) has a dramatic impact on the outcomes.Recent studies have provided a glimpse at certain pathways including pulmonary vasospasm,remodeling of the pulmonary vessel wall,intenstitial lung disease,endothelial dysfunction,imbalance of vasodilators and vasoconstrictors,inflammatory pathways and autoimmunity,in situ thrombosis,gene polymorphism and so on that contribute to the development of PAH in CTD,but the pathogenesis of pulmonary arterial hypertension related to connective tissue diseases (CTD-PAH) has not yet been elucidated.In this paper,the progress in this regard are reviewed.

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

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    Baumann Gert

    2005-09-01

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

  12. Unaltered membrane properties of arterial muscle in Dahl strain genetic hypertension.

    Science.gov (United States)

    Abel, P W; Trapani, A; Matsuki, N; Ingram, M J; Ingram, F D; Hermsmeyer, K

    1981-08-01

    To characterize membrane properties of arterial muscle from Dahl strain hypertensive rats, we measured caudal artery contractile sensitivity to norepinephrine and serotonin, membrane potential at 16 and 37 degrees C, and intracellular potassium, sodium, and chloride content. Dahl salt-resistant (R) strain fed low- or high-salt diets and Dahl salt-sensitive (S) strain fed a low-salt diet remained normotensive. The Dahl S strain on high-salt diets became hypertensive after 4 wk of high salt feeding. There was no significant difference in the norepinephrine or serotonin effective concentration (EC) EC50, EC10, or maximum response between the hypertensive and any of the three normotensive groups. Membrane potential measured at 37 and 16 degrees C and electron-probe analysis of intracellular potassium, sodium, and chloride concentration showed no significant differences between the four groups of animals. These results that arterial muscle membrane mechanisms are not altered in genetically hypertensive Dahl salt-sensitive rats.

  13. [Analysis of the timing parameters of blood flow in the carotid basin arteries of hypertensive patients].

    Science.gov (United States)

    Makarenko, E S

    2011-01-01

    Vascular duplex ultrasound study with simultaneous ECG recording was performed to estimate the timing parameters of blood flow in the common carotid, internal carotid, and middle cerebral arteries in patients with grades 1 and 2 arterial hypertension. There was an increase in the blood flow acceleration phase index in the common carotid and middle cerebral arteries and a reduction in the systolic phase index in the internal carotid arteries. There were correlations of phasic blood flow parameters in the extra- and intracranial arteries with age and lipidogram readings.

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

    Science.gov (United States)

    Hardin, Elizabeth Ashley; Chin, Kelly M

    2016-01-01

    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.

  15. Diminished contractile responses of isolated conduit arteries in two rat models of hypertension.

    Science.gov (United States)

    Zemancíková, Anna; Török, Jozef

    2013-08-31

    Hypertension is accompanied by thickening of arteries, resulting in marked changes in their passive and active mechanical properties. The aim of this study was to demonstrate that the large conduit arteries from hypertensive individuals may not exhibit enhanced contractions in vitro, as is often claimed. Mechanical responses to vasoconstrictor stimuli were measured under isometric conditions using ring arterial segments isolated from spontaneously hypertensive rats, N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated Wistar rats, and untreated Wistar rats serving as normotensive control. We found that thoracic aortas from both types of hypertensive rats had a greater sensitivity but diminished maximal developed tension in response to noradrenaline, when compared with that from normotensive rats. In superior mesenteric arteries, the sensitivity to noradrenaline was similar in all examined rat groups but in L-NAME-treated rats, these arteries exhibited decreased active force when stimulated with high noradrenaline concentrations, or with 100 mM KCl. These results indicate that hypertension leads to specific biomechanical alterations in diverse arterial types which are reflected in different modifications in their contractile properties.

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

    Directory of Open Access Journals (Sweden)

    Saptanaga Kumar

    2015-04-01

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

  17. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis

    Science.gov (United States)

    Evans, Jonathan D W; Girerd, Barbara; Montani, David; Wang, Xiao-Jian; Galiè, Nazzareno; Austin, Eric D; Elliott, Greg; Asano, Koichiro; Grünig, Ekkehard; Yan, Yi; Jing, Zhi-Cheng; Manes, Alessandra; Palazzini, Massimiliano; Wheeler, Lisa A; Nakayama, Ikue; Satoh, Toru; Eichstaedt, Christina; Hinderhofer, Katrin; Wolf, Matthias; Rosenzweig, Erika B; Chung, Wendy K; Soubrier, Florent; Simonneau, Gérald; Sitbon, Olivier; Gräf, Stefan; Kaptoge, Stephen; Di Angelantonio, Emanuele; Humbert, Marc; Morrell, Nicholas W

    2016-01-01

    Summary Background Mutations in the gene encoding the bone morphogenetic protein receptor type II (BMPR2) are the commonest genetic cause of pulmonary arterial hypertension (PAH). However, the effect of BMPR2 mutations on clinical phenotype and outcomes remains uncertain. Methods We analysed individual participant data of 1550 patients with idiopathic, heritable, and anorexigen-associated PAH from eight cohorts that had been systematically tested for BMPR2 mutations. The primary outcome was the composite of death or lung transplantation. All-cause mortality was the secondary outcome. Hazard ratios (HRs) for death or transplantation and all-cause mortality associated with the presence of BMPR2 mutation were calculated using Cox proportional hazards models stratified by cohort. Findings Overall, 448 (29%) of 1550 patients had a BMPR2 mutation. Mutation carriers were younger at diagnosis (mean age 35·4 [SD 14·8] vs 42·0 [17·8] years), had a higher mean pulmonary artery pressure (60·5 [13·8] vs 56·4 [15·3] mm Hg) and pulmonary vascular resistance (16·6 [8·3] vs 12·9 [8·3] Wood units), and lower cardiac index (2·11 [0·69] vs 2·51 [0·92] L/min per m2; all p<0·0001). Patients with BMPR2 mutations were less likely to respond to acute vasodilator testing (3% [10 of 380] vs 16% [147 of 907]; p<0·0001). Among the 1164 individuals with available survival data, age-adjusted and sex-adjusted HRs comparing BMPR2 mutation carriers with non-carriers were 1·42 (95% CI 1·15–1·75; p=0·0011) for the composite of death or lung transplantation and 1·27 (1·00–1·60; p=0·046) for all-cause mortality. These HRs were attenuated after adjustment for potential mediators including pulmonary vascular resistance, cardiac index, and vasoreactivity. HRs for death or transplantation and all-cause mortality associated with BMPR2 mutation were similar in men and women, but higher in patients with a younger age at diagnosis (p=0·0030 for death or transplantation, p=0·011

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

    Directory of Open Access Journals (Sweden)

    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

  19. Successful pregnancy in pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Streit Michael

    2009-06-01

    Full Text Available Abstract Introduction Pulmonary arterial hypertension is a complication of systemic lupus erythematosus. Mortality in pregnant patients with pulmonary arterial hypertension related to connective tissue disease is as high as 56%. The authors report the first case of a successful maternal-fetal outcome in a pregnant patient with systemic lupus erythematosus-associated pulmonary arterial hypertension treated with sildenafil and inhaled iloprost during pregnancy and until several weeks after caesarean section. Case presentation The case presented is of a 29-year-old woman with systemic lupus erythematosus and associated severe pulmonary arterial hypertension. Vasodilator therapy with bosentan and sildenafil, immunosuppressive therapy with prednisone, hydroxychloroquine and azathioprine and oral anticoagulation (phenprocoumon had normalized her right ventricular over right atrial pressure when she was diagnosed in her 5th week of pregnancy. The teratogenic drugs bosentan and phenprocoumon were stopped, the latter replaced by low molecular weight heparin. During the 35th week, a slight increase in pulmonary pressure was found. Therapy with inhaled iloprost was established. A caesarean section was performed in the 37th week and a healthy baby was delivered. The patient remained stable until 11 weeks after delivery, when an increase in right ventricular over right atrial pressure was noted. Bosentan was reintroduced and prednisone and azathioprine doses were increased. The patient has remained stable until the present time. Conclusion Pulmonary arterial hypertension has been considered a contraindication for pregnancy. Novel vasodilator therapy, combined with immunosuppressants in this patient with systemic lupus erythematosus, may "cure" pulmonary arterial hypertension and permit pregnancy with successful outcome. However, postpartum exacerbation of systemic lupus erythematosus and pulmonary arterial hypertension have to be considered.

  20. 肺动脉高压靶向药物治疗进展%Advances in the targeted therapy for pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    张晓春; 管丽华; 潘文志; 李明飞; 常晓鑫; 周达新

    2014-01-01

    Pulmonary arterial hypertension (PAH) is deifned as a change of the structure and/or function of pulmonary vascular bed caused by a variety of reasons resulting in a clinical syndrome characterized by a progressive increase in pulmonary vascular resistance and finally leading to the expansion of right ventricular, heart failure, and even death. The prognosis of patients with pulmonary arterial hypertension has been signiifcantly improved along with the recent emerging of targeted drugs. The advances in the targeted therapy for pulmonary arterial hypertension are summarized in this review.%肺动脉高压是指由各种原因引起的肺血管床结构和/或功能的改变,导致以肺血管阻力进行性升高为特点的临床综合症。最终致使右室扩张,引起心力衰竭,甚至死亡。近年来,靶向药物的出现使肺动脉高压患者预后得到明显改善。本文概括介绍肺动脉高压靶向药物的治疗进展。

  1. The Na+/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension.

    Science.gov (United States)

    Huetsch, John C; Jiang, Haiyang; Larrain, Carolina; Shimoda, Larissa A

    2016-03-01

    Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a key component of the vascular remodeling underlying the development of pulmonary hypertension (PH). Stimuli such as growth factors and hypoxia induce PASMC alkalinization, proliferation, and migration through upregulation of the Na(+)/H(+) exchanger (NHE), inhibition of which prevents the development of hypoxia-induced vascular remodeling and PH. We wanted to explore whether NHE was also necessary for pathologic PASMC proliferation and migration in a model of pulmonary arterial hypertension (PAH), a severe form of PH not associated with persistent hypoxia. PASMCs were isolated from rats exposed to SU5416-hypoxia (SuHx) followed by return to normoxia and from vehicle controls. We measured resting intracellular pH (pHi) and NHE activity using the pH-sensitive fluorescent dye BCECF-AM. PASMC proliferation and migration were assessed using BrdU incorporation and transwell filters, respectively. NHE activity was increased in SuHx PASMCs, although resting pHi was unchanged. SuHx PASMCs also exhibited increased proliferation and migration relative to controls, which was attenuated in the setting of pharmacologic inhibition of NHE. Our findings suggest that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH, although this effect does not appear to be mediated by global changes in pHi homeostasis.

  2. ORGANOPROTECTIVE EFFECTS OF BENASEPRIL IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. S. Zadionchenko

    2006-01-01

    Full Text Available Aim. To evaluate antihypertensive efficiency of benasepril therapy (Lotensin, Novartis and its effects on microcirculation, endothelium function, system of cytoprotection, ophthalmoscopic and functional characteristics of eye retina in patients with arterial hypertension (AH. Material and methods. 40 patients with AH of 1-3 degree (AH1, AH2, and AH3 were studied. After wash-out period all patients were prescribed benasepril 5-10 mg daily. If necessary, hydrochlorothiazide 12,5 mg daily was added. Treatment lasted during 6 months. Patients were examined at the beginning and at the end of the study. Ambulatory blood pressure (BP monitoring was carried out. Microcirculation was assessed by method of laser Doppler flowmetry. Stable plasma metabolites of nitric oxide (NO were determined by spectral photometry. Cytoprotection was assessed by content of heat shock proteins (HSP70 in leucocytes of peripheral blood. Ophthalmoscopy, color and contrast static campimetry with evaluation of sensory-motor reaction (SMR time in different fields of vision were carried out. Results. Therapy with benasepril allowed to improve daily profile of BP and to reach its target level in all AH patients. Number of patients with spastic type of microcirculation decreased. Functional condition of endothelium improved which revealed in normalization of endothelial production of NO. Therapy with benasepril resulted in intracellular HSP70 level decrease which testified restriction of cellular destruction. The cytoprotective effect of benasepril was stronger in patient with severe AH. Therapy with benasepril resulted in SMR time decrease which signifies its positive influence on retinal blood flow. Evaluation of contrast and color sensitiveness of retina allowed to reveal and quantitatively assess earlier dysfunctions of retinal tissue perfusion, compared to ophthalmoscopy. Conclusion. Benasepril is an efficient antihypertensive drug which improves microcirculation, endothelium

  3. Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights.

    Science.gov (United States)

    Dardi, Fabio; Manes, Alessandra; Palazzini, Massimiliano; Bachetti, Cristina; Mazzanti, Gaia; Rinaldi, Andrea; Albini, Alessandra; Gotti, Enrico; Monti, Enrico; Bacchi Reggiani, Maria Letizia; Galiè, Nazzareno

    2015-08-01

    Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

  4. 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.

  5. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Waleska C Dornas; Marcelo E Silva

    2011-09-01

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

  6. Effect of induced hypertension on experimentally-induced cerebral arterial spasm.

    Directory of Open Access Journals (Sweden)

    Shimata,Kenji

    1984-04-01

    Full Text Available Ten adult cats were anesthetized and ventilated by respirator. After the basilar artery was exposed transclivally and visualized with an operative microscope, mean arterial blood pressure (MABP was raised gradually by intravenous drip infusion of norepinephrine (5-20 micrograms/kg or angiotensin-II-amide (0.3-1.0 micrograms/kg. At various blood pressures, microphotographs were taken. There was no appreciable change in vessel diameter at a MABP ranging from 78 to 191 mmHg. The blood pressure was allowed to return to the initial baseline level. Arterial spasm was produced by the topical application of 0.2 M calcium gluconate, which decreased the arterial diameter by 13 to 58 percent for more than 60 min. Blood pressure was increased again after the production of the arterial spasm. Significant increases in the diameter of the arteries were produced by the drug-induced hypertension at levels of MABP ranging from 82 to 192 mmHg. The maximum arterial dilations ranged from 123 to 208 percent of the untreated control. The degree of dilation of the arteries almost paralleled the rise in MABP. Norepinephrine and angiotensin-II had a similar effect on both the blood pressure and the arterial diameter. Induced hypertension would be expected to improve blood flow parameters in the case of spastic cerebral arteries.

  7. Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T

    2012-01-01

    Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hype......Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA......)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10±1 × 10(3) to 17±2 × 10(3) μm(2); 6 weeks: 13±2 × 10(3) to 24±3 × 10(3) μm(2)). After 3, but not 6, weeks of hypertension, the arterial diameter...... hypertensive rats did show a significant diameter increase (Ø: 419±13 to 475±16 μm). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean Ø between 235 and 290 μm), and infiltration of monocyte/macrophages. SOL1 treatment did not affect the arterial diameter of LF...

  8. Pulmonary hypertension in patients with hematological disorders following splenectomy.

    Science.gov (United States)

    Meera, V; Jijina, Farah; Ghosh, Kanjaksha

    2010-03-01

    Prevalence of pulmonary arterial hypertension (PAH) was studied by Echocardiography and Doppler in 43 splenectomised patients with various disorders 1-20 years after splenectomy. PAH was detected only in thalassemia major, intermedia, hereditary sphereocytosis and myelofibrosis groups comprising a total of 21 patients. Six patients out of 21 was found to have PAH with mean pulmonary arterial pressure of 46.28 ± 28.17 mmHg. Twenty one controls having similar duration and type of disease also were assessed for PAH in this case control study 3/21 had PAH in this control group. The difference in number of patients showing pulmonary hypertension between case and control was not statistically significant (chi-square test p = 0.29-though the difference in pulmonary arterial pressure between case and control were significantly different (t-test psideroblastic anemia, extra hepatic portal hypertension, autoimmune hemolytic anemia did not show PAH after splenectomy even years after the procedure PAH following splenectomy is common after certain disorders and control patients with these diseases have tendency to develop PAH even without splenectomy. Pulmonary thromboembolism may be an important pathophysiological mechanism leading to this condition. Patients having hemolytic anemia and myelofibrosis should have regular evaluation of pulmonary arterial pressure whether he/she has been splenectomised or not. This is particularly important as availability of phosphodiesterase inhibitors like sildenafil allows one to manage these cases.

  9. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Holst, J J; Moller, S

    2000-01-01

    Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin...... concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied...... during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng...

  10. AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension.

    Science.gov (United States)

    Said, Karim

    2015-01-01

    It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial hypertension patients and many questions remain to be answered. One of these vital questions is whether the strategy of upfront initiation of combination therapy could improve patients outcomes compared to the strategy of initial monotherapy. The recently published AMBITION trial represents an important forward step towards answering this question by comparing a strategy of first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in patients with pulmonary arterial hypertension.

  11. Research progress on role of immuno-inflammatory response in pulmonary artery hypertension%免疫炎症反应在肺动脉高压中作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    张惠芳; 方莲花; 杜冠华

    2015-01-01

    Abstrcat:Pulmonary artery hypertension ( PAH) is a cardiopul-monary disease with extensive obliterative changes in the small to midsized pulmonary arterioles. This review summarizes the al-tered inflammation and immune processes underlying the devel-opment of PAH, and discusses inflammatory factors, immune cells, Rho kinase and gene implicated in PAH. Preclinical stud-ies have provided the basis for abnormal immune response in ani-mal models of the PAH, and this paper, based on inflammatory/immune response mechanisms, proposes PAH potential therapeu-tic targets.%肺动脉高压( pulmonary artery hypertension,PAH)是一种伴有中、小肺动脉阻塞的心肺疾病。该文查阅国内外最近的研究文献,介绍PAH中免疫炎症反应的改变,阐述炎症因子、免疫细胞、Rho激酶和基因在PAH疾病的发生和发展的重要作用。大量临床前和临床研究已经证明PAH动物模型中免疫反应的异常,该文将以免疫炎症反应机制为基础,提出治疗或缓解PAH疾病的新的治疗策略和途径,为寻找和发现PAH潜在的药物靶点提供理论依据。

  12. Increased arterial distensibility and renovascular hypertension in Goldenhar syndrome Aumento de distensibilidade arterial e hipertensão renovascular na Sindrome de Goldenhar

    OpenAIRE

    Drager, Luciano F.; Hélio Bernardes Silva; Bortolotto, Luiz A

    2005-01-01

    This is a report of the successful angioplastic treatment of an association of renovascular hypertension with renal artery stenosis and the Goldenhar syndrome (a variant of oculoauriculovertebral dysplasia). For the first time to date, this association, which occurred in a 13-year-old girl, is reported. Additionally, increased arterial distensibility in spite of arterial hypertension was detected by noninvasive methods. The similarity of this finding and in those for other genetic diseases, s...

  13. Arterial Hypertension and other risk factors associated with cardiovascular diseases among adults

    OpenAIRE

    Cremilde Aparecida Trindade Radovanovic; Lucimary Afonso dos Santos; Maria Dalva de Barros Carvalho; Sonia Silva Marcon

    2014-01-01

    OBJECTIVE: to identify the prevalence of arterial hypertension and its association with cardiovascular risk factors among adults. METHOD: cross-sectional, population-based, descriptive study conducted with 408 adult individuals. Data were collected through a questionnaire and measurements of weight, height and waist circumference. Person's Chi-square and multiple logistic regression were used in the data analysis. RESULTS: 23.03% of the individuals reported hypertension with a higher prevalen...

  14. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    Directory of Open Access Journals (Sweden)

    M. V. Leonova

    2012-01-01

    Full Text Available Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

  15. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    Directory of Open Access Journals (Sweden)

    M. V. Leonova

    2015-12-01

    Full Text Available Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

  16. Glucometabolic abnormalities survey among outpatients without previous diabetes diagnosis and with coronary artery disease and hypertension

    Institute of Scientific and Technical Information of China (English)

    陈韵岱

    2014-01-01

    Objective To explore the status of glucometabolic abnormalities in cardiological outpatients without previous diabetes diagnosis and with coronary artery disease(CAD)and hypertension.Methods Patients without previous diagnosis of diabetes but with hypertension and CAD aged 18 years or above were recruited from cardiology departments of 11 general hospitals in China.Demographic data,disease diagnosis and medical history were collected.Physical examination and questionnaire survey were

  17. Clinical and psychological characteristics of patients with arterial hypertension, consuming an increased amount of salt

    OpenAIRE

    O. B. Poselyugina

    2015-01-01

    Objective: to Study the potential development of links between the formation of neurotic disorders personality and high salt intake (S) with food in patients with arterial hypertension (AH).Materials and methods: the study involved 229 patients with essential hypertension. We determined the threshold of taste sensitivity to salt (TTS), the daily excretion of sodium ions in urine, was assessed psychological status of the patients, the type of attitude to the disease (LOBI), the severity of dep...

  18. Queixa de vertigem e hipertensão arterial Vertigo complaint and blood hypertension

    Directory of Open Access Journals (Sweden)

    Luciana Lozza de Moraes Marchiori

    2007-03-01

    Full Text Available OBJETIVO: investigar a presença de queixa de vertigem em pacientes de meia idade com hipertensão arterial. MÉTODOS: estudo do tipo prospectivo, transversal. Composto por 154 indivíduos de ambos os gêneros com idade de 45 a 64 anos. A hipertensão foi verificada por meio de medição da pressão arterial e de questionário sistematizado sobre hipertensão e uso de medicamentos para pressão arterial. A queixa de vertigem foi verificada por meio de anamnese audiológica. RESULTADOS: pode-se verificar que existe associação significante entre hipertensão arterial e queixa de vertigem. CONCLUSÃO: os resultados da presente pesquisa, por meio da constatação da associação entre hipertensão arterial e queixa de vertigem, servirão de base a profissionais da área de saúde que estão envolvidos com sintomas provenientes da hipertensão arterial.PURPOSE: to investigate the presence of vertigo complaint in middle-aged hypertension patients. METHODS: a transversal study. Composed by 154 patients of both genders, aged from 45 to 64 years, included in the research after sample estimation. Hypertension was verified through blood pressure readings and by a systematized questionnaire about hypertension and the use of medication for blood pressure. Vertigo was assessed through audiological anamneses. RESULTS: there is a significant association between blood hypertension and vertigo. CONCLUSION: the results in this research, through evidence of association between blood hypertension and vertigo complaint, can be a base for health professionals concerned with alterations caused by blood hypertension.

  19. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension.

    Science.gov (United States)

    Kossmann, Sabine; Lagrange, Jeremy; Jäckel, Sven; Jurk, Kerstin; Ehlken, Moritz; Schönfelder, Tanja; Weihert, Yvonne; Knorr, Maike; Brandt, Moritz; Xia, Ning; Li, Huige; Daiber, Andreas; Oelze, Matthias; Reinhardt, Christoph; Lackner, Karl; Gruber, Andras; Monia, Brett; Karbach, Susanne H; Walter, Ulrich; Ruggeri, Zaverio M; Renné, Thomas; Ruf, Wolfram; Münzel, Thomas; Wenzel, Philip

    2017-02-01

    Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin αMβ2- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in

  20. [Analysis of efficacy and safety of administration of moxonidine in patients with arterial hypertension and hypertensive crises].

    Science.gov (United States)

    Gaponova, N I; Abdrakhmanov, V R; Baratashvili, V L; Tereshchenko, S N

    2011-01-01

    In the review we present detailed analysis of antihypertensive action of 3-nd generation sympatholytic moxonidine. Due to selective interaction with imidazoline I1-receptors moxonidine diminishes sympathetic activity causing lowering of peripheral vascular resistance. This leads to significant lowering of systolic and diastolic arterial pressure. Efficacy and safety of the drug has been shown both for the management of uncomplicated hypertensive crises and long term treatment of arterial hypertension (AH). Appropriateness of the use of moxonidine in patients with AH combined with diabetes mellitus, metabolic syndrome, chronic obstructive pulmonary disease has been confirmed. Moxonidine is well tolerated; its bioavailability after oral intake reaches 90%. The drug produces neither hypotensive "first dose" nor rebound effects.

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

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

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

  2. The effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease: optimal pharmacotherapy.

    Science.gov (United States)

    Morishita, Yoshiyuki; Kusano, Eiji

    2013-03-01

    The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of progression of arterial hypertension, chronic kidney disease (CKD) and cardiovascular disease (CVD). Previous studies suggested that a direct renin inhibitor, aliskiren, may be effective for blood pressure lowering, renoprotection and cardiovascular protection. This review focuses on the effects of aliskiren for arterial hypertension, CKD and CVD.

  3. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    OpenAIRE

    Salvatore Rosanio; Francesco Pelliccia; Carlo Gaudio; Cesare Greco; Abdul M. Keylani; D’Agostino, Darrin C.

    2014-01-01

    This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance t...

  4. [Analysis of changes in characteristics of arterial hypertension occupational risk in workers of nonferrous metallurgy].

    Science.gov (United States)

    Vlasova, E M; Shliapnikov, D M; Lebedeva, T M

    2015-01-01

    The article covers changes in occupational cardiovascular risk for workers of nonferrous,metallurgy. Findings are that exposure to noise up to 94 dB with length of service increases possible atherosclerosis and metabolic syndrome. With 5 years of service, risk of the predicted conditions increases by 40.5%. When occupational exposure lasts over 5 years, risk of arterial hypertension increases. A group of workers without exposure to occupational factors appeared to have no connection between length of service and metabolic syndrome and arterial hypertension. Risk evolution modelling proved that risk of functional disorders in nonferrous metallurgy workers becomes unacceptable after 5 years of service (cardiovascular disorders are critical).

  5. Management of Sepsis in Patients with Pulmonary Arterial Hypertension in the Intensive Care Unit.

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    Tartavoulle, Todd M

    2017-03-01

    Pulmonary arterial hypertension is a lethal condition, and the management of sepsis in patients with pulmonary arterial hypertension is challenging. As the disease progresses, the right ventricle is susceptible to failure due to a high pulmonary vascular resistance. The limited ability of the right ventricle to increase cardiac output in septic shock makes it difficult to deliver oxygen to the organ and tissues. Intravascular volume replacement and vasoactive drugs should only be considered after a thorough assessment. Priorities of care include improving cardiac output and oxygen delivery by optimizing preload, reducing afterload, and improving contractility.

  6. Hipertensão arterial pulmonar associada à anemia falciforme Sickle cell anemia-associated pulmonary arterial hypertension

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    Roberto Ferreira Pinto Machado

    2007-10-01

    Full Text Available A hipertensão pulmonar é uma complicação comum em pacientes com anemia falciforme. A despeito das elevações leves das pressões pulmonares desses pacientes, a morbimortalidade é alta e, em pacientes adultos com anemia falciforme, a hipertensão pulmonar é um fator de risco muito importante. A patogênese da hipertensão pulmonar relacionada à anemia falciforme é multifatorial e inclui hemólise, baixos níveis de óxido nítrico, hipóxia crônica, tromboembolismo, doença hepática crônica e asplenia. Na maioria dos pacientes, a hipertensão arterial pulmonar é a causa principal para as elevações na pressão arterial pulmonar, mas a hipertensão pulmonar venosa também é um fator contribuinte em alguns pacientes. Existem poucos estudos específicos avaliando os efeitos de tratamento para a hipertensão pulmonar em pacientes com anemia falciforme. É provável que a intensificação da terapia para a anemia hemolítica em todos os pacientes e o tratamento específico para a hipertensão pulmonar em pacientes com doença severa sejam benéficos. Estudos de grande porte avaliando o efeito do tratamento da hipertensão pulmonar em pacientes com anemia falciforme estão em andamento.Pulmonary hypertension is a common complication of sickle cell anemia. Despite the fact that the elevations in pulmonary artery pressures are slight, morbidity and mortality are high. In adult sickle cell anemia patients, pulmonary hypertension is emerging as a major risk factor for death. The pathogenesis of sickle cell anemia-related pulmonary hypertension is multifactorial, including hemolysis, impaired nitric oxide bioavailability, chronic hypoxemia, thromboembolism, chronic liver disease and asplenia. In the majority of patients, pulmonary arterial hypertension is the main cause of elevated pulmonary artery pressures. However, pulmonary venous hypertension also plays a role in a subgroup of patients. Specific data on the effects of treatment

  7. Light and scanning electron microscopic and immunohistochemical studies on permeability of hypertensive rat mesenteric arteries.

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    Suzuki, K; Kawaharada, U; Takatama, M; Ooneda, G

    1985-09-01

    Experimental hypertensive rats were intravenously injected with carbon and iron as tracers, and their mesenteric arteries exhibiting hypertensive arterial lesions were observed by light and scanning electron microscopy and immunohistochemistry. Early arterial lesions showing intense medial damages, deposition of fibrinoid substance consisting of fibrin in the intima and/or media, and granulation tissue in the adventitia were characterized by marked insudation of intravenously injected tracers. Scanning electron microscopy demonstrated numerous leukocytes and platelets adhering to endothelial surface, opened endothelial cell junctions, and desquamation of these cells. Immunohistochemistry revealed laminin and low stainability of fibronectin in the subendothelium. Advanced lesions showed deposition of a large amount of fibrinoid substance and no insudation of tracers in the intima, but scanning electron microscopy manifested opening of endothelial cell junctions, desquamation of endothelial cells, and adherence of leukocytes and platelets. Immunohistochemistry revealed fibronectin in the intima and laminin just beneath the endothelium. In the healed lesions disclosing fibrocellular intimal thickening, there was no insudation of tracers. Scanning electron microscopy showed opened endothelial cell junctions, endothelial cell defects, and adherence of leukocytes and platelets. There were fibronectin in the intima and laminin beneath the endothelium. It was suggested that the opening of endothelial cells junctions and desquamation of endothelial cells would be necessary for the arterial increased permeability in hypertensive rats, and that fibrin-fibronectin complex, fibronectin-acid mucopolysaccharide complex, and basement membrane would together inhibit the increased permeability in the mesenteric arteries of hypertensive rats in spite of endothelial cell injuries and their defects.

  8. Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension

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    YanYun Pan

    2015-05-01

    Full Text Available Background/Aims: Transplantation of endothelial progenitor cells (EPCs plays a therapeutic role in pulmonary arterial hypertension (PAH. Meanwhile, recruitment of progenitors has potential inflammatory effects and exaggerates vascular injury. CD40 pathway is identified as a major player in vascular inflammatory events. In this study, we investigated the role of CD40 pathway in regulating early outgrowth EPC functions, and searched for improvements in PAH cell therapy. Methods: EPCs were isolated from rat bone marrow and cultured for 7 days. After treatment with soluble CD40 ligand (sCD40L for 24 hours, EPC migration, adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat PAH model was founded by subcutaneous injection of monocrotaline (MCT. Control EPCs or lentivirus vectors (Lv-shRNA-CD40 EPCs were infused via tail vein at day 7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28. Results: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation, and vasculogenesis functions. However, paracrine effects of soluble intercellular adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were dose-dependently improved by sCD40L. Control EPC-derived conditioned medium protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones showed detrimental effects. After MCT injection, sCD40L levels in rat serum increased gradually. Other than in vitro results, benefits of both two EPC treatments were obvious, even taken at day 21. Benefits of control EPCs wore off over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as characterized by both ameliorated rat hemodynamic and reversed vascular remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better, rather than into adventitia and media. Conclusion: sCD40L impaired protective effects of EPCs. Traditional EPC treatments were limited in PAH, while interruption of CD

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

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    Chuanchen Zhang

    2016-01-01

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

  10. Clinical analysis of 59 cases with connective tissue disease associated pulmonary arterial hypertension%结缔组织病相关性肺动脉高压59例临床分析

    Institute of Scientific and Technical Information of China (English)

    李杰; 刘双; 杨京华; 许尚栋

    2013-01-01

    Objective: To understand the incidence, clinical features and prognosis of connective tissue disease (CTD) associated pulmonary arterial hypertension (PAH) , increase awareness and attention about the disease. Methods: all cases with pulmonary arterial hypertension in 715 cases with connective tissue disease were analyzed retrospectively. Results;The overall incidence rate of CTD-associated PAH is about8. 3%. In 59 CTD-associated PAH cases, there are 47 female cases and 12 male cases, aged 23 to 95 years with the mean age of (57 ± 19) years. The duration is 0. 1 to 30 years, and the average duration is (7. 4 ±7. 3) years. A-mong these cases, Behcet s disease had the highest incidence of pulmonary hypertension; it is 19. 2% , followed by systemic lupus erythematosus (13. 7% ) , Sjogren's syndrome (13. 5% ) , rheumatoid arthritis (7. 4% ) , ar-teritis (3.5%, P < 0. 01) . Age and pulmonary artery pressure was negatively correlated (correlation coefficient r = - 0. 490, P < 0. 01) ; The proportions of interstitial lung disease, anti-nuclear antibody ( ANA) -positive rates, rheumatoid factor (RF) positive rates between PAH group and non-PAH group had statistical difference (P < 0. 05). Conclusion: PAH is a common complication in connective tissue disease. In our study, Behcet's disease and systemic lupus erythematosus had the highest incidence of PAH; earlier age of onset, more serious PAH; the patients with pulmonary fibrosis, elevated inflammatory indicators, positive ANA and RF are more likely to suffer CTD-associated PAH.'%目的:了解结缔组织病(connective tissue diseases,CTD)相关的肺动脉高压(pulmonary arterial hypertension,PAH)的发生率、临床特点及预后,提高对该病的认识及重视.方法:从715例CTD患者中筛选出伴有PAH的患者59例,对其临床资料进行回顾性分析.结果:合并的PAH的总发生率约为8.3%.59例患者中女性47例,男性12例;年龄23~95岁,平均(57±19)岁;病程1个月~ 30年.其中

  11. Plumbagin reverses proliferation and resistance to apoptosis in experimental PAH.

    Science.gov (United States)

    Courboulin, Audrey; Barrier, Marjorie; Perreault, Tanya; Bonnet, Pierre; Tremblay, Veronique L; Paulin, Roxane; Tremblay, Eve; Lambert, Caroline; Jacob, Maria H; Bonnet, Sandra N; Provencher, Steeve; Bonnet, Sébastien

    2012-09-01

    Like cancer, pulmonary arterial hypertension (PAH) is characterised by a pro-proliferative and anti-apoptotic phenotype. In PAH, pulmonary artery smooth muscle cell (PASMC) proliferation is enhanced and apoptosis suppressed. The sustainability of this phenotype requires the activation of pro-survival transcription factors, such as signal transducer and activator of transcription (STAT)3 and nuclear factor of activated T-cells (NFAT). There are no drugs currently available that are able to efficiently and safely inhibit this axis. We hypothesised that plumbagin (PLB), a natural organic compound known to block STAT3 in cancer cells, would reverse experimental pulmonary hypertension. Using human PAH-PASMC, we demonstrated in vitro that PLB inhibits the activation of the STAT3/NFAT axis, increasing the voltage-gated K(+) current bone morphogenetic protein receptor type II (BMPR2), and decreasing intracellular Ca(2+) concentration ([Ca(2+)](i)), rho-associated coiled-coil containing protein kinase (ROCK)1 and interleukin (IL)-6, contributing to the inhibition of PAH-PASMC proliferation and resistance to apoptosis (proliferating cell nuclear antigen (PCNA), TUNEL, Ki67 and anexine V). In vivo, PLB oral administration decreases distal pulmonary artery remodelling, mean pulmonary artery pressure and right ventricular hypertrophy without affecting systemic circulation in both monocrotaline- and suden/chronic hypoxia-induced PAH in rats. This study demonstrates that the STAT3/NFAT axis can be therapeutically targeted by PLB in human PAH-PASMC and experimental PAH rat models. Thus, PLB could be considered a specific and attractive future therapeutic strategy for PAH.

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

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    Fadel Elie

    2011-09-01

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

  13. Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence?

    Science.gov (United States)

    Bernatova, Iveta

    2014-01-01

    Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  14. Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone-system in arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G. (AN Ukrainskoj SSR, Kiev)

    1985-01-01

    In 110 patients suffering from various forms of arterial hypertension (hypertension, aldosteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone were measured. Basal values of aldosterone, renin activity in blood as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography were determined. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute Lasix (furosemide) stress was evaluated. It was found, that the system renin-angiotensin-aldosterone is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hours rhythm of their concentrations in serum and the reaction to acute Lasix stress. The radioimmunoassays of quantitative parameters of the renin-angiotensin-aldosterone system are decisive for the differential diagnosis of hypertension and adrenal gland tumors connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medications for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medications and surgery.

  15. Pulmonary hypertension with a huge thrombosis in main stem of pulmonary artery

    Institute of Scientific and Technical Information of China (English)

    杨萍; 曾红; 孟繁波; 赵林阳

    2001-01-01

    @@A huge thrombosis in the main stem of the pulmonary artery (PA) with pulmonary hypertension has rarely been reported. We present two cases diagnosed and treated in our hospital. One suffered from polyarteritis with a huge thrombus in PA revealed at autopsy. The second case had congenital heart disease of the patent artery duct; and the huge thrombus was found on echocardiogram and extirpated in surgery.

  16. Regression of pulmonary artery hypertension due to development of a pulmonary arteriovenous malformation

    Science.gov (United States)

    Hasan, Ashfaq; Sastry, B.K.S.; Aleem, M.A.; Reddy, Gokul; Mahmood, Syed

    2014-01-01

    Idiopathic Pulmonary Hypertension (IPAH) is characterized by elevated pulmonary arterial pressure in the absence of an identifiable underlying cause. The condition is usually relentlessly progressive with a short survival in the absence of treatment.1 We describe a patient of IPAH in whom the pulmonary artery pressures significantly abated with complete disappearance of symptoms, following spontaneous development of a pulmonary arterio-venous malformation (PAVM). PMID:25443608

  17. 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.

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

    Science.gov (United States)

    Shao, Dongmin; Perros, Frédéric; Caramori, Gaetano; Meng, Chao; Dormuller, Peter; Chou, Pai-Chien; Church, Colin; Papi, Alberto; Casolari, Paolo; Welsh, David; Peacock, Andrew; Humbert, Marc; Adcock, Ian M; Wort, Stephen J

    2014-08-15

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

  19. Progress on pathogenesis and targeted therapy in pulmonary arterial hypertension%肺动脉高压发生机制及靶向治疗进展

    Institute of Scientific and Technical Information of China (English)

    马慧

    2015-01-01

    Pulmonary arterial hypertension is a disease characterized by vasospasm,intimal hyperplasia and re-modeling of pulmonary arterioles. Recently,the use of targeted medicine has improved the prognosis of PAH patients to some extent. Currently,the three classical targeted drugs include endothelin receptor antagonists,phosphodiesterase-5 in-hibitors and prostaglandin analogues. In this review,we summarized the advances of pathogenesis and targeted therapy in PAH.%肺动脉高压( PAH)是以肺小动脉的血管痉挛、内膜增生和重构为主要特征的一种疾病。目前治疗PAH的三大经典途径的靶向药物包括内皮素受体拮抗剂、5型磷酸二酯酶抑制剂和前列腺素类似物。最近研究发现,新型靶向药物可在一定程度上改善PAH的预后。本文就PAH发生的分子机制及靶向药物治疗进行综述。

  20. What does the time constant of the pulmonary circulation tell us about the progression of right ventricular dysfunction in pulmonary arterial hypertension?

    Science.gov (United States)

    Bellofiore, A; Wang, Z; Chesler, N C

    2015-06-01

    Compliance (C) and resistance (R) maintain a unique, inverse relationship in the pulmonary circulation, resulting in a constant characteristic time [Formula: see text] that has been observed in healthy subjects as well as patients with pulmonary arterial hypertension (PAH). However, little is known about the dependence of right ventricular (RV) function on the coupled changes in R and C in the context of this inverse relationship. We hypothesized three simple dependencies of RV ejection fraction (RVEF) on R and C. The first model (linear-R) assumes a linear RVEF-R relation; the second (linear-C) assumes a linear RVEF-C relation; and the third one combines the former two in a mixed linear model. We found that the linear-R model and the mixed linear model are in good agreement with clinical evidence. A conclusive validation of these models will require more clinical data. Longitudinal data in particular are needed to identify the time course of ventricular-vascular impairment in PAH. Simple models like the ones we present here, once validated, will advance our understanding of the mechanisms of RV failure, which could improve strategies to manage RV dysfunction in PAH.

  1. The System of Neutrophil Elastase and the Plasma Level of MMP-7 in Children with Pulmonary Arterial Hypertension and Chronic Cor Pulmonale

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    Еlena M. Vasilyeva

    2014-03-01

    Full Text Available A significant increase in the activity of neutrophil elastase (NE and anti-NE-protection in the plasma were detected in children having bronchopulmonary dysplasia (BPD complicated by pulmonary arterial hypertension (PAH and chronic cor pulmonale (CCP. The changes revealed were more pronounced in patients with CCP. The plasma concentration of the NE was slightly reduced, which was probably associated with the activation of anti-NE and an increase in the α1-antitrypsin level. A gradual increase was noted in the plasma level of the matrix metalloproteinase-7 (MMP-7 in patients with an increase in the severity of the condition. In patients with cystic fibrosis (with and without CCP, the pronounced increase in the MMP-7 level was observed. In patients with cystic fibrosis (CF, even without the additional complication with PAH and CCP, the MMP-7 level was significantly higher than in those with congenital broncho-pulmonary malformations (CBPM. The difference was increased in those patients with PAH and reached a maximum in those with CCP.

  2. Arterial Hypertension in a Child with Williams-Beuren Syndrome (7q11.23 Chromosomal Deletion

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    Cristina de Sylos

    2002-08-01

    Full Text Available We report the case of a 7-year-old male child diagnosed with Williams-Beuren syndrome and arterial hypertension refractory to clinical treatment. The diagnosis was confirmed by genetic study. Narrowing of the descending aorta and stenosis of the renal arteries were also diagnosed. Systemic vascular alterations caused by deletion of the elastin gene may occur early in individuals with Williams-Beuren syndrome, leading to the clinical manifestation of systemic arterial hypertension refractory to drug treatment.

  3. 儿童肺动脉高压64例临床分析%CLINICAL ANALYSIS OF PULMONARY ARTERIAL HYPERTENSION IN 64 CHILDREN

    Institute of Scientific and Technical Information of China (English)

    杨芳; 林志; 钟日荣

    2011-01-01

    目的 分析儿童肺动脉高压(pulmonary arterial hypertension,PAH)的临床资料,以提高对该病的认识.方法 对64例包含PAH诊断患儿的临床表现、辅助检查、诊疗过程进行回顾性分析,并复习相关文献.结果 ①64例患儿中57例(89.06%)为先天性心脏病相关PAH.左向右分流型先天性心脏病49例,其中11例经内科治疗,肺部感染、心力衰竭难以控制,肺动脉压力较另38例高[分别为(9.15±2.87)、(6.68±2.49)kPa,t=2.800 1,P<0.05],49例中除2例死亡外,余47例术后随访6个月~1年,肺动脉压力均降至正常;复杂型先天性心脏病相关PAH 8例,术后肺动脉压力较术前下降[分别为(5.36±1.53)、(8.77±2.61)kPa,t=-3.564 3,P<0.05].②2例(3.13%)为腺样体肥大引起PAH,肺动脉压力分别为16.08、16.91kPa,予以腺样体切除后,1例肺动脉压力降至正常,1例肺动脉压力较术前有所下降(10.67kPa),但仍较正常高.③2例(3.13%)为结缔组织病合并PAH,其中1例为系统性红斑狼疮,1例为幼年特发性关节炎,肺动脉压力分别为16.8、14.4kPa,2例均死亡.④3例(4.68%)为特发性PAH,肺动脉压力分别为14.67、8.88、10.67kPa,自动出院.结论 儿童PAH可由多种原因引起,需积极查找病因,及时治疗,可改善预后.%Objective To analyze the clinical data of pulmonary arterial hypertension( PAH )in children in order to improve the recognition of this disease. Methods The clinical manifestation,auxiliary examination, diagnosis and treatment of 64 pediatric inpatients with PAH were analyzed retrospectively,and the relative literatures were reviewed. Results ① In 64 pediatric inpatients with PAH,57( 57/64,89.06% )cases were congenital heart disease- associated PAH( CHD- PAH ), left to right shunt CHD was 49 cases. Among 49 cases, 11 cases 'pulmonary inffection, cardiac failure were hard to control permedical treatment, their pulmonary arterial pressure( PAP )were higher than the other 38 cases'[ ( 9.15±2.87 )k

  4. Structural and functional changes of the coronary arteries in elderly senile patients with essential hypertension.

    Science.gov (United States)

    Hu, Jun; Zhu, Fu; Xie, Jun; Cheng, Xinhai; Chen, Guiyu; Tai, Haifen; Fan, Shaohua

    2013-11-01

    The aim of this study was to evaluate the effect of aging on the changes to the structure and function of coronary arteries in senile elderly patients with essential hypertension. Patients (aged 60-80 years) were divided into three groups. The 195 hypertensive patients were divided into four sub-groups according to the duration of hypertension. The changes to the coronary arteries (left and right) of all those patients were tested using the following index by 64 coronary computed tomography (CT) scans. The 24 h systolic blood pressure (SBP) and other blood biochemical parameters were assayed for all patients. We found that the value of the body mass index (BMI), total cholesterol (TC) and low density lipoproteins (LDL) were lower, but age and high density lipoproteins (HDL) were higher in the group of very elderly patients with hypertension (Group I; Phypertension (Group III). The left anterior descending branch calcification score (CSLAD), total calcification score (CST), pulse pressure (PP), the left main branch calcification score (CSLM), the left circumflex branch calcification score (CSLCX) were significantly increased in Group I compared with Group III (Phypertension' group (Group II). Hence, in elderly patients, a decrease in the levels of BMI, HDL, TC and LDL accompanies aging. Furthermore, the decline of arterial compliance and increase in arterial stiffness develops with age. Aging is more likely to lead to atherosclerosis in the coronary arteries, particularly in the left main coronary artery and its main branches. Aging is an uncontrollable risk factor, which plays a crucial role in coronary artery atherosclerosis.

  5. SY 18-1 TRANSLATIONAL RESEARCH IN PAH.

    Science.gov (United States)

    Chung, Wook-Jin

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome.Korean Registry of Pulmonary Arterial Hypertension (KORPAH) is the first modern PAH registries in Asian ethnicity. Total 39 centers participated and 625 patients were enrolled. This study evaluated the incidence, prevalence, epidemiology, therapeutic modalities and survival data of Korean patients with PAH."Gachon experiences" was to characterize the clinical outcomes and evaluate the factors influencing survival time of the PAH patients in Korean. This study compared the cumulative survival of total 43 PAH patients who received targeted or conventional therapy.PAH Ilopost BMPR-2 gene in Korea IIT Multi-institutional (PILGRIM) is a prospective, investigator-initiative, and multi-institutional clinical trials. This study was recently completed in March by 7 institutes, and aimed to investigate (1) the prevalence of BMPR-2 gene mutations in the Korean PAH patients and (2) the effect of iloprost inhalation solution on hemodynamic response, and exercise echocardiography.PAH basic research focuses on two major themes: (1) Systematic comparison of the effects of adipose tissue, bone marrow and umbilical cord blood-derived mesenchymal stem cell transplantation on MCT-induced PAH in rats and (2) investigation of the effect of human UCB-derived MSC (hUCB-MSC) transplantation combined with apelin-13 administration on MCT-induced PAH in rats. Data suggests that, although the

  6. Intrapulmonary arteries respond to serotonin and adenosine triphosphate in broiler chickens susceptible to idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Kluess, H A; Stafford, J; Evanson, K W; Stone, A J; Worley, J; Wideman, R F

    2012-06-01

    This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.

  7. Peripheral artery disease: a cause of refractory hypertension after renal transplantation.

    Science.gov (United States)

    Dourado, Raquel; Gonçalves, Pedro de Araújo; Almeida, Manuel; Weigert, André; Bruges, Margarida; Gaspar, Augusta; Negrão, Acácio Pita; Machado, Domingos; Clemente, Belarmino; Teles, Rui; Machado, Francisco Pereira; Silva, Aniceto

    2008-03-01

    The authors report the case of a 44-year-old man, with a history of hypertension, smoking, peripheral artery disease and chronic renal failure. After renal transplantation, the patient developed persistent high blood pressure, despite optimal medical therapy. When angiotensin-converting enzyme (ACE) inhibitor therapy was begun, he developed acute anuric renal failure, which was reversed after interruption of the ACE inhibitor. After the initial clinical evaluation, the patient was referred for renal angiography, which revealed critical stenosis of the proximal left common iliac artery, just above the renal graft artery anastomosis. The patient underwent successful angioplasty and stenting of the lesion, with complete normalization of blood pressure.

  8. Meta analysis of the changes of arterial stiffness of hypertension patients with CCB or ARB

    Institute of Scientific and Technical Information of China (English)

    张艺军

    2013-01-01

    Objective To evaluate the differences of the changes of arterial stiffness of hypertension patients with the treatment of calcium channel blocker(CCB) or angiotensin Ⅱ receptor blocker(ARB). Methods Based on the principles of evidence-based medicine,corresponding inclusion

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  10. Is arterial hypertension crucial for the development of cerebral haemorrhage in premature infants?

    DEFF Research Database (Denmark)

    Lou, H C; Lassen, N A; Friis-Hansen, B

    1979-01-01

    . It is suggested that premature neonates are hypertensive when their blood-pressure is compared with that in utero, and that events that lead to further rises in pressure are common. Their capillaries are not protected against rises in arterial pressure because autoregulation is impaired. Furthermore...

  11. Isolated agenesis of the right pulmonary artery with late manifestation of pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Huebsch, P.; Pichler, W.; Lang, I.; Mlczoch, J.

    1987-01-01

    The case of a woman patient of 25 years of age with acute cardiac decompensation is presented. The chest X-ray as well as the lung scan showed the typical features of absence of the right pulmonary artery. The diagnosis was confirmed angiographically. The sudden and late onset of symptoms of pulmonary hypertension is a remarkable feature.

  12. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, O

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population...

  13. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Holst, J J; Møller, Søren;

    2000-01-01

    during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng...

  14. СHOICE OF ZOFENOPRIL AND HYDROCHLOROTHIAZIDE COMBINATION IN THE TREATMENT OF ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. A. Dzhaiani

    2011-01-01

    Full Text Available Problems of antihypertensive therapy are discussed in the light of the present epidemiological situation with arterial hypertension. ACE inhibitors have a special place among the antihypertensive drugs. Advantages and evidence base of ACE inhibitors representative — zofеnopril highlighted. Special attention is given to combined antihypertensive therapy , particularly combination of zofenopril and hydrochlorothiazide.

  15. Autoregulation of brain circulation in severe arterial hypertension

    DEFF Research Database (Denmark)

    Strandgaard, S; Olesen, Jes; Skinhoj, E

    1973-01-01

    beyond which an increase of cerebral blood flow above the resting value was seen without clinical symptoms. No evidence of vasospasm was found in any patient at high blood pressure. These observations may be of importance for the understanding of the pathogenesis of hypertensive encephalopathy.......Cerebral blood flow was studied by the arteriovenous oxygen difference method in patients with severe hypertension and in normotensive controls. The blood pressure was lowered to study the lower limit of autoregulation (the pressure below which cerebral blood flow decreases) and the pressure limit...... of brain hypoxia. Both limits were shifted upwards in the hypertensive patients, probably as a consequence of hypertrophy of the arteriolar walls. These findings have practical implications for antihypertensive therapy.When the blood pressure was raised some patients showed an upper limit of autoregulation...

  16. Comparison of the therapeutic and side effects of tadalafil and sildenafil in children and adolescents with pulmonary arterial hypertension.

    Science.gov (United States)

    Sabri, Mohammad Reza; Beheshtian, Elham

    2014-04-01

    Pulmonary arterial hypertension (PAH) is a progressive disease. In recent years, phosphodiesterase type 5 inhibitors such as sildenafil have been used to treat this disease in children. Recently, tadalafil has been used in adults with similar efficacy but it has been used less often in children. This experimental study was carried out in 18 known patients aged 4-24 years in the Emam Hossein Hospital of Isfahan, Iran. All patients had been taking sildenafil for a few months to years. Patients underwent echocardiographic study, the 6-minute walk test (6MWT), and non-invasive pulse oximetry before and after the 6MWT. These tests were repeated again after sildenafil had been switched to tadalafil for 6 weeks. After 6 weeks of tadalafil prescription, the severity of some of the patients' symptoms decreased, but the New York Heart Association class of the patients did not change more. Mean ± standard deviation (SD) oxygen saturation while taking sildenafil and after 6 weeks of tadalafil were significantly different (p = 0.005). Furthermore, mean ± SD oxygen saturation after the 6MWT while taking sildenafil and after 6 weeks of tadalafil were significantly different (p = 0.036). The mean ± SD distances walked in this test while taking sildenafil and tadalafil were significantly different (p = 0.005). No significant side effects were seen; 15 patients continued tadalafil. Tadalafil may be a safe drug to treat children and young adults with PAH. We did not observe any significant side effects during usage; it improves functional capacity and oxygen saturation better than sildenafil in these patients, and requires fewer daily doses than sildenafil.

  17. Rationale and methodology of monitoring ambulatory blood pressure and arterial compliance in the Hypertension in the Very Elderly Trial

    OpenAIRE

    2006-01-01

    OBJECTIVE: This article describes the rationale and methodology for the monitoring of ambulatory blood pressure and arterial compliance in hypertensive patients aged 80 years and above. This is a side project of the Hypertension in the Very Elderly Trial. METHODS: The hypertension in the Very Elderly Trial is a multicentre, double-blind, randomized, placebo-controlled trial aiming to investigate the effect of active treatment on cardiovascular and other outcomes in hypertensive patients aged ...

  18. Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

    Science.gov (United States)

    Fransen, Paul; Van Hove, Cor E; Leloup, Arthur J A; Schrijvers, Dorien M; De Meyer, Guido R Y; De Keulenaer, Gilles W

    2016-02-01

    Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

  19. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

    Directory of Open Access Journals (Sweden)

    Iveta Bernatova

    2014-01-01

    Full Text Available Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP. The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (prehypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  20. Plasma homocysteine is associated with aortic arterial stiffness but not wave reflection in Chinese hypertensive subjects.

    Directory of Open Access Journals (Sweden)

    Wenkai Xiao

    Full Text Available OBJECTIVE: Elevated plasma total homocysteine (tHcy acts synergistically with hypertension to exert a multiplicative effect on cardiovascular diseases risk. The aim of this study was to determine the relationship between tHcy concentration and blood pressure, and to evaluate the role of plasma tHcy in arterial stiffness and wave reflection in hypertension. METHODS: In this cross-sectional study, a community-based sample of 1680 subjects (mean age 61.6 years was classified into four groups according to tHcy level (<21.6 vs. ≥ 21.6 µmol/l and blood pressure (hypertensive vs. normotensive. Levels of plasma tHcy and other biochemical parameters (e.g., lipids, glucose were determined. Central arterial blood pressure, reflected pressure wave, and carotid-femoral pulse wave velocity (cf-PWV were assessed by tonometry within 2 days of obtaining the blood specimen. RESULTS: Neither peripheral nor central blood pressure differed according to tHcy levels in normotensive and hypertensive subjects. Differences in cf-PWV according to tHcy were observed only in hypertensive subjects; differences in cf-PWV in normotensive subjects were not significant after adjusting for confounding factors. Central augmentation index did not differ according to tHcy level in either normotensive or hypertensive subjects. Results of univariate analysis revealed significant correlations between blood pressure parameters and tHcy concentration only among normotensive subjects; however, these correlations were not significant in a partial correlation analysis. Results of multiple regression analysis showed that plasma tHcy levels were independently correlated with cf-PWV in hypertensive subjects (β = 0.713, P = 0.004. The independent relationship between tHcy and central augmentation index was not significant by further multiple analyses in normotensive or hypertensive individuals. CONCLUSIONS: Plasma tHcy level is strongly and independently correlated with arterial

  1. 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.

  2. 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

  3. TELMISARTAN IN THE TREATMENT OF ARTERIAL HYPERTENSION. CASE STUDY

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2012-01-01

    Full Text Available Data on angiotensin II receptor blockers, one of the main drug classes used in cardiology , are presented. The advantages of this drugs class are highlighted with the focus on telmisartan. Additionally clinical example of successful telmisartan application in patients with hypertension, high risk of cardiovascular complications, and obesity is presented.

  4. Tropical pulmonary eosinophilia presenting as severe pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Shikha Jindal

    2013-01-01

    Full Text Available Tropical pulmonary eosinophilia (TPE is an easily diagnosed and treatable disease. Patients with TPE usually present with respiratory symptoms that include paroxysmal cough, breathlessness, wheeze and chest pain, often misdiagnosed as bronchial asthma. This case highlights one of the unusual presentations of TPE and discusses the association between TPE and pulmonary hypertension.

  5. 妊娠合并肺动脉高压患者的妊娠结局分析%Pregnancy outcomes of 103 women with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    李斌; 孙晓媛; 王克芳

    2013-01-01

    Objective To evaluate the pregnancy outcome of women with pulmonary arterial hypertension (PAH).Methods The medical records of 103 pregnant women with PAH admitted to Beijing Anzhen Hospital from January 2007 to March 2011 were studied retrospectively.Results (1) Degree of PAH and cardiac function.Among the 103 PAH,92 cases were patients with congenital heart disease and 13 cases were with rheumatic heart disease.They were divided by color doppler ultrasound into mild PAH group (34 cases),moderate PAH group (22 cases) and severe PAH group (47 cases).Per heart function classification,21 cases (20.4%,21/103) were class Ⅰ,44 cases (42.7%,44/103) were class Ⅱ,27 cases (26.2%,27/103) were class Ⅲ and 11 cases (10.7%,11/103) were class Ⅳ.More patients were class Ⅲ and Ⅳcardiac function in the severe PAH group than in the mild and moderate PAH groups,with statistically significant difference (P < 0.05).(2) Delivery mode.There were 44 term delivery and 23 preterm birth in the 103 PAH patients.Sixty-three cases (94%,63/67) received cesarean section and 4 cases had vaginal delivery.There were 36 iatrogenic abortion (35.0%,36/103).The iatrogenic abortion rate in the severe PAH group was significantly higher than those in the mild and moderate PAH groups (P < 0.05).(3) Perinatal outcomes.The full-term delivery rates in the mild and moderate PAH groups [80% (20/25) and 14/17] were significantly higher than the severe PAH group (40%,10/25),respectively (P < 0.05).And the premature birth rate of the severe PAH group(60%,15/25) was significantly higher than the mild and moderate PAH group [20% (5/25)and 3/17,P < 0.05].There were 4 neonatal asphyxia.The birth weight of mild,moderate and severe PAH groups were (3071 ± 443),(2910 ± 619) and (2381 ±589) g,respectively.The birth weight in the severe PAH group was significantly lower than the mild and moderate PAH groups (P < 0.05).(4) Mortality.Nine cases naternal death happened,with a

  6. Renal artery stenosis: An unusual etiology of hypertensive encephalopathy in a child with fanconi anemia

    Directory of Open Access Journals (Sweden)

    Radheshyam Purkait

    2015-01-01

    Full Text Available A 9-year-old girl, diagnosed case of Fanconi anemia, presented with generalized convulsion with altered sensorium. She had fever, severe pallor, sinus tachycardia, blood pressure of 180/120 mmHg in both upper and lower limb, pan-systolic murmur of grade 2/6, abdominal bruit and bilateral papilledema. A provisional diagnosis of hypertensive encephalopathy was made and managed with continuous labetalol infusion. Detailed evaluation including magnetic resonance angiography of renal artery detected underlying atrophic and non-functioning right kidney secondary to severe renal artery stenosis on the same side. She was started with multiple antihypertensives, but her blood pressure was maintained poorly. Later on, she underwent rightsided nephrectomy. Following surgery, she was doing well and maintaining normal blood pressure without any antihypertensives. Our child is the second reported case of Fanconi anemia associated with renal artery stenosis presenting with hypertensive encephalopathy.

  7. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    Directory of Open Access Journals (Sweden)

    Rabahi MF

    2015-07-01

    Full Text Available Marcelo Fouad Rabahi,1,2 Sheila Alves Pereira,1 José Laerte Rodrigues Silva Júnior,1,2 Aline Pacheco de Rezende,1 Adeliane Castro da Costa,2 Krislainy de Sousa Corrêa,2,3 Marcus Barreto Conde4,5 1School of Medicine, Federal University of Goiás, Goiania, Brazil; 2Clínica do Aparelho Respiratório (CLARE, Goiania, Brazil; 3Pontifical Catholic University of Goiás, Goiania, Brazil; 4Faculdade de Medicina de Petrópolis/FASE, Petrópolis, Brazil; 5Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Background: The diagnosis of chronic obstructive pulmonary disease (COPD is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods: This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results: Of a total of 570 subjects, 316 (55% met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7% patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3% reported no respiratory symptoms; 41 (17.6% patients with arterial hypertension and at least one respiratory symptom, and 10 (12% patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24. The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100% than among those with respiratory symptoms (56.1% (P=0.01. Conclusion: Our findings suggest that

  8. ASSESSMENT OF AWARENESS LEVEL OF OWN DISEASE IN PATIENTS WITH STABLE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    G. F. Andreeva

    2005-01-01

    Full Text Available Arterial hypertension (AH is the most frequent risk factor of cardiovascular diseases and related mortality in all developed countries. Altough therapy with antihypertensive drugs significantly reduces this risk, patients with stable mild hypertension have poor compliance with the treatment. The reasons and levels of inadequacy of antihypertensive therapy in this group of patients are well-known.Aim. To evaluate the awareness level of own disease, adequacy of therapy only in those patients with stable mild arterial hypertension, who are complied with recommendations of physicians concerning AH treatment and changing of mode of life. It was also planned to reveal possible grounds for inadequate secondary prevention of cardiovascular disease.Materials and methods. 76 patiens with stable mild arterial hypertension were included into study. They didn’t have any serious concomitant diseases and were complied with the recommendations of physicians concerning secondary prevention of cardiovascular disease. Questionnaire of State Research Center for Preventive Medicine “Assessment of awareness level of own disease in patients with stable arterial hypertension” was used in the study.Results. It was revealed, that the majority of patients, invoved in the study, were nonsmokers and regularly took antihypertensive drugs. 70% of questioned patients reached the target arterial blood pressure levels, while patients with arterial hypertension in general Russia population received regular and efficient treatment in less than 30-20%. Drugs treatment of questioned patients almost didn’t differ from that, which received patients in out-patient clinics of Moscow: in both cases ACE inhibitors were preferred. Only 29% of questioned patients knew their lipid levels in blood and none of the patients took drugs, reducing levels of lipids in blood. Half of the patients, that took part in our study, had increased level of body mass index.Conclusions. Inadequate

  9. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension.

    Science.gov (United States)

    Mackenzie, Isla S; McEniery, Carmel M; Dhakam, Zahid; Brown, Morris J; Cockcroft, John R; Wilkinson, Ian B

    2009-08-01

    Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening. Although various drug therapies are used to lower peripheral blood pressure (BP) in patients with isolated systolic hypertension, the effects of the 4 major classes of antihypertensive agents on central BP, pulse pressure (PP) amplification, and arterial stiffness in this condition are not clear. Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension (systolic BP > or =140 mm Hg and diastolic BP hypertension, the choice of therapy may be influenced by these findings in the future.

  10. Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

    Science.gov (United States)

    Zaveljcina, Janez; Legan, Mateja; Gaberšček, Simona

    2016-05-01

    We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension.

  11. [State of the dopamine system activity, as one of factors for the development of arterial hypertension and obesity].

    Science.gov (United States)

    Lyzogub, V H; Dolynna, O V; Bogdan, T V; Sobol', V O

    2012-01-01

    The discovery of 5 subtypes of dopamine receptors revealed their important role in development of arterial hypertension and obesity. Reduce of their functional activity or number with age conduces to the increase of tone of the sympathetic nervous system, dyspoiesis of leptin, hyperphagia, development of obesity and arterial hypertension. Prescription of dopamine agonists conduces to reduction of in, normalization of leptin, diminishing of appetite and body mass, decrease of blood pressure. Combination of arterial hypertension and obesity is recommended to determine dopamine excretion and to appoint dopamine agonists at level of < 600 nmol/24 hours.

  12. Hypertension and depression Hipertensão arterial sistêmica e depressão

    Directory of Open Access Journals (Sweden)

    Andréia Zavaloni Scalco

    2005-06-01

    Full Text Available Despite the high prevalence of depression and hypertension, the relationship between the two diseases has received little attention. This paper reviews the epidemiological, pathophysiological, and prognostic aspects of this association, as well as its implications for treatment. A Medline search was conducted using the following key words: depression, blood pressure, blood pressure variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive agents, and genetics, from 1980 to 2004. We found descriptions of increased prevalence of hypertension in depressed patients, increased prevalence of depression in hypertensive patients, association between depressive symptomatology and hypotension, and alteration of the circadian variation of blood pressure in depressed patients. There is considerable evidence suggesting that hyperreactivity of the sympathetic nervous system and genetic influences are the underlying mechanisms in the relationship between depression and hypertension. Depression can negatively affect the course of hypertensive illness. Additionally, the use of antidepressive agents can interfere with blood pressure control of patients with hypertension by inducing changes in blood pressure and orthostatic hypotension.Apesar das altas prevalências de hipertensão arterial sistêmica e de depressão, o estudo da relação entre depressão e pressão arterial tem recebido pouca atenção da literatura. Nesse artigo são revisados os aspectos epidemiológicos, patofisiológicos, prognósticos e implicações no tratamento, relacionados à associação entre depressão e hipertensão arterial sistêmica. O método utilizado foi consulta ao banco de dados bibliográficos Medline, utilizando-se as palavras chave depression, blood pressure, blood pressure variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive agents e genetics, no período de 1980 a 2004. Encontramos descrições de

  13. Low occurrence of digital ulcers in scleroderma patients treated with bosentan for pulmonary arterial hypertension: a retrospective case-control study.

    Science.gov (United States)

    Cozzi, F; Pigatto, E; Rizzo, M; Favaro, M; Zanatta, E; Cardarelli, S; Riato, L; Punzi, L

    2013-05-01

    Digital ulcers (DU) are one of the most common and debilitating manifestations of vasculopathy in systemic sclerosis (SSc). Their prevention is important in order to improve patients' outcome and as a result of the economic impact they have on society. Randomised controlled studies have demonstrated that bosentan, an endothelin receptor antagonist, reduces the appearance of new DU. The aim of this retrospective study was to evaluate the occurrence of DU in a group of patients receiving long-term bosentan treatment for pulmonary arterial hypertension associated with SSc (PAH-SSc). Patients with PAH-SSc and treated with bosentan for at least 6 months (n = 30) were evaluated. Thirty patients with SSc not treated with bosentan, but matched for sex, age, disease duration and cutaneous form of SSc, were considered as a control group. The occurrence of DU, defined as loss of tissue of varying degrees in the epidermis, dermis and subcutaneous tissue, was determined in the bosentan-treated and untreated groups. Mean duration of bosentan treatment was 3.6 years. DU were detected in six patients in the bosentan-treated group (20.0 %) and 16 patients (53.3 %) in the untreated group (p = 0.0015). There were no significant differences in demographic or clinical characteristics between patients with or without DU at study end. The occurrence of DU in patients with PAH-SSc receiving long-term bosentan treatment was significantly lower than in untreated patients. The results from this long-term observational study provide valuable information on management of patients with PAH-SSc.

  14. Arterial wall stiffness in patients with essential hypertension at young age

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    Kolesnik E.L.

    2014-11-01

    Full Text Available Research objective was investigating arterial wall stiffness in patients with hypertension at young age and assessing the relationship between subclinical target organs damage and ambulatory blood pressure monitoring (ABPM parameters. 30 male patients aged 18-35 years with essential hypertension stage I and II, hypertension 1 and 2nd grade were surveyed. The examination included general clinical methods, echocardiography, ABPM and suprasystolic sfigmography. It was found that the pulse wave velocity (PWVao (r = 0,557 p <0,01, central aortic blood pressure (SBPao (r = 0,492 p <0,01 and augmentation index (AIxao (r = 0,489 p <0.01 significantly increased with the pa¬tients’ age. Abdominal obesity (r = 0,566 p <0,01 and BMI (r = 0,599 p <0,01 impacted on the PWVao acceleration. Increasing of the left ventricular mass index (LVMI is highly associated with SBPao (r = 0,506 p <0,05 and PWVao (r = 0,434 p <0,05. According to ABPM the most significant correlation with arterial wall stiffness parameters demon¬strated diastolic blood pressure (DBP daytime level (AIxao (r = 0,418 p <0,01, with PWVao (r = 0,699 p <0.01 and SBPao (r = 0,695 p <0,01. Thus, age, excessive body weight and obesity should be considered as unfavorable factors that worsen arterial wall stiffness in patients with hypertension at the age before 35 years. Increase of DBP levels especially during the day causes maximum negative impact on the arterial wall stiffness parameters according to ABPM. Increased SBPao and PWVao in patients with hypertension at a young age are associated with increased left ventricular mass index.

  15. Subclinical arterial and cardiac damage in white-coat and masked hypertension.

    Science.gov (United States)

    Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Olszanecka, Agnieszka; Klima, Łukasz; Gąsowski, Jerzy; Grodzicki, Tomasz; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2016-08-01

    The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians.

  16. Evaluation of the pharmacological treatment of arterial hypertension associated to heart failure in Camarones town.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Milián Vázquez.

    2006-12-01

    Full Text Available Background: Arterial hypertension is a risk factor for many cardiovascular and cerebrovascular diseases. Objective: To evaluate the pharmacological treatment in patients with arterial hypertension, also suffering from heart failure. Methods: A descriptive-prospective study was carried out, this consisted in the use of prescription-indication drugs through a simple random sample study of 43 patients, representing the 35.2 % in six Family Clinical Units of the urban area of Camarones’ Communitarian Policlinic, Palmira, Cienfuegos, during the first semester of 2004. Results: the 51.2 % of the patients were included in the class II of the New York Heart Asociation’s classification, and the 55.8% were considered hypertense class II. The hypertensive drugs more used were the captopril and the clortalidone, and among the drugs associated to the hypertensive ones it was included the isosorbide dinitrate, the digoxin and the acetylsalicylic acid. The 87.3 % of the patients received a correct dose, and in the 88.9% it was followed an adequate administration interval. The prescription was considered adequate in the 65.1 % of the studied patients. Conclusions: the advances in the treatment of these diseases are due to different factors, even though the study shows that the treatment of the patient of the series is adecuate, it should be bettered as long as possible.

  17. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    Science.gov (United States)

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

  18. Transforming growth factor-beta1 upregulation triggers pulmonary artery smooth muscle cell proliferation and apoptosis imbalance in rats with hypoxic pulmonary hypertension via the PTEN/AKT pathways.

    Science.gov (United States)

    Liu, Yun; Cao, Yonggang; Sun, Shuyang; Zhu, Jinquan; Gao, Shan; Pang, Jie; Zhu, Daling; Sun, Zengxian

    2016-08-01

    Transforming growth factor-beta1 (TGFβ1) and Phosphatase and Tensin homolog deleted on chromosome ten (PTEN) are involved in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. In previous studies, we have shown that TGFβ1 and PTEN play an important role in the progression of pulmonary vascular remodeling induced by pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms involved in the activation of PASMCs between TGFβ1 and PTEN pathways remain unknown. We found that pulmonary vascular walls in hypoxic pulmonary arterial hypertension (PAH) rats were thicker than the vessels from normal rats in vivo. Substantially higher levels of TGFβ1 and significant loss of PTEN expression were observed in the lungs of PAH rats when compared with normoxia. Meanwhile, AKT, a downstream proliferative signaling protein of the PTEN antagonist PI3K, was markedly activated in the lungs of PAH rats. In vitro studies using PASMCs showed that TGFβ1 increased cell proliferation in PTEN-dependent manner. Moreover, we found that TGFβ1 enhanced cell survival, up-regulated the expression of Bcl-2 and procaspase-3, decreased the number of TUNEL-positive cells and caspase-3 expression in PASMCs under serum-deprived (SD) condition via PI3K/AKT pathway. The results further establish that TGFβ1 promoted PAH by decreasing PTEN expression and increasing PI3K/AKT activation in the lung. In conclusion, TGFβ1 mediated PTEN inactivation and resistance to apoptosis seems to be key mediators of lung vascular remodeling associated with PAH. These findings further clarify molecular mechanisms that support targeting PTEN/AKT signaling pathway to attenuate pathogenic derangements in PAH.

  19. Comparison of the effectiveness of oral sildenafil versus oxygen administration as a test for feasibility of operation for patients with secondary pulmonary arterial hypertension.

    Science.gov (United States)

    Ajami, Gholam Hossein; Borzoee, Mohammad; Radvar, Mohammad; Amoozgar, Hamid

    2008-05-01

    It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). In this study we determined the effectiveness of sildenafil and compared its efficacy with inhaled nasal oxygen (O2) during cardiac catheterization in patients with congenital heart diseases (CHD) and PAH, as a test of feasibility for surgical repair of the patients. We studied 15 patients, 9 male and 6 female, with a mean age of 8.3 years. Hemodynamic measurements were made at baseline, after O2 administration for 20 min (5 L/min by mask), and then 45 min after administration of a single dose of sildenafil (0.5 mg/kg orally or via nasogastric tube). Mean PAP at baseline was 72.2 +/- 12.54 mm Hg and was reduced by sildenafil to 52.5 +/- 9.6 and by O2 to