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Sample records for arterial hypertension pah

  1. The economic burden of pulmonary arterial hypertension (PAH) in the US on payers and patients

    OpenAIRE

    Sikirica, Mirko; Iorga, Serban R; Bancroft, Tim; Potash, Jesse

    2014-01-01

    Background Pulmonary arterial hypertension (PAH) is a rare condition that can ultimately lead to right heart failure and death. In this study we estimated the health care costs and resource utilization associated with PAH in a large US managed care health plan. Methods Subjects with claims-based evidence of PAH from 1/1/2004 to 6/30/2010 (identification period) were selected. To be included in the final PAH study sample, subjects were required to have ≥2 claims with a primary PH diagnosis; ≥2...

  2. Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?

    OpenAIRE

    Stewart Simon; Dalton Brad; Wlodarczyk John; Strange Geoff; Steele Peter; Gabbay Eli; Keogh Anne

    2010-01-01

    Abstract Background Pulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients. Method...

  3. Hemodynamics in pulmonary arterial hypertension (PAH: do they explain long-term clinical outcomes with PAH-specific therapy?

    Directory of Open Access Journals (Sweden)

    Stewart Simon

    2010-02-01

    Full Text Available Abstract Background Pulmonary arterial hypertension (PAH has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients. Methods We performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH Registry to estimate long-term survival with each therapy. Results Ten RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH, 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%. Conclusion When applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH

  4. Pulmonary arterial hypertension.

    OpenAIRE

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should ...

  5. Idiopathic pulmonary arterial hypertension

    OpenAIRE

    Firth, Amy L.; Mandel, Jess; Yuan, Jason X.-J.

    2010-01-01

    Despite improved understanding of the pathobiology of pulmonary arterial hypertension (PAH), it remains a severe and progressive disease, usually culminating in right heart failure, significant morbidity and early mortality. Over the last decade, some major advances have led to substantial improvements in the management of PAH. Much of this progress was pioneered by work in animal models. Although none of the current animal models of pulmonary hypertension (PH) completely recapitulate the hum...

  6. 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.

  7. Gestational pulmonary arterial hypertension

    OpenAIRE

    Moll, Matthew; Payne, Julie G.; Tukey, Melissa H.; Farber, Harrison W.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease marked by the irreversible pulmonary vascular changes of vasoconstriction, thrombosis, and proliferation of smooth muscle and endothelial cells. The untreated clinical course is characterized by progressive dyspnea and a median survival of less than 3 years. Many of these patients are of child-bearing age; however, pregnancy leads to physiologic changes that are particularly poorly tolerated in PAH, conferring a 30%–56% mortality....

  8. 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

  9. MicroRNAs in Pulmonary Arterial Hypertension

    OpenAIRE

    Zhou, Guofei; Chen, Tianji; Raj, J. Usha

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertensi...

  10. Left main coronary artery compression in pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Al-Badri, Kadhem Helo Abbas; Jensen, Jesper Møller; Christiansen, Evald H;

    2015-01-01

    In patients with pulmonary arterial hypertension (PAH), chest pain is most likely due to right ventricular demand ischemia. We report a patient with idiopathic PAH who developed severe angina due to extrinsic compression of the left main coronary artery (LMCA) from a dilated pulmonary artery trunk...

  11. Pulmonary arterial hypertension: an update

    OpenAIRE

    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 and specific histological changes. It is a progressive disease finally resulting in right heart failure and premature death. Typical symptoms are dyspnoea at exercise, chest pain and syncope; furthe...

  12. Anticoagulation in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522

  13. 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.

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

    OpenAIRE

    Humbert, M.

    2010-01-01

    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 cont...

  15. Pulmonary arterial hypertension associated with systemic sclerosis

    OpenAIRE

    Mathai, Stephen C.; Hassoun, Paul M.

    2011-01-01

    Systemic sclerosis (SSc) is commonly complicated by pulmonary arterial hypertension (PAH), which is a leading cause of death in the SSc patient population. Owing to the fact that the risk of developing pulmonary hypertension is high, screening is important, although the optimal modality remains to be defined. Furthermore, despite recent advances in therapy for PAH, the response to these interventions in patients with PAH with SSc has been discouraging. The lack of clinical response to these t...

  16. Pulmonary arterial hypertension.

    Science.gov (United States)

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

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

  17. Drugs induced pulmonary arterial hypertension.

    Science.gov (United States)

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized 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 appetite suppressant 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 arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  18. An Update on Pulmonary Arterial Hypertension

    OpenAIRE

    Wapner, Joanna; Matura, Lea Ann

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. PAH is defined as a mean pulmonary arterial pressure ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an extensive history, serology, chest radiograph, pulmonary function tests, ventilation/perfusion scan, transthoracic echocardiogram, and right heart catheterization. Treatment and care of p...

  19. MicroRNAs in pulmonary arterial hypertension.

    Science.gov (United States)

    Zhou, Guofei; Chen, Tianji; Raj, J Usha

    2015-02-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  20. 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 ...

  1. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

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

  2. Erythropoietin upregulation in pulmonary arterial hypertension.

    Science.gov (United States)

    Karamanian, Vanesa A; Harhay, Michael; Grant, Gregory R; Palevsky, Harold I; Grizzle, William E; Zamanian, Roham T; Ihida-Stansbury, Kaori; Taichman, Darren B; Kawut, Steven M; Jones, Peter L

    2014-06-01

    The pathophysiologic alterations of patients with pulmonary arterial hypertension (PAH) are diverse. We aimed to determine novel pathogenic pathways from circulating proteins in patients with PAH. Multianalyte profiling (MAP) was used to measure 90 specifically selected antigens in the plasma of 113 PAH patients and 51 control patients. Erythropoietin (EPO) functional activity was assessed via in vitro pulmonary artery endothelial cell networking and smooth muscle cell proliferation assays. Fifty-eight patients had idiopathic PAH, whereas 55 had other forms of PAH; 5 had heritable PAH, 18 had connective tissue disease (15 with scleroderma and 3 with lupus erythematosis), 13 had portopulmonary hypertension, 6 had PAH associated with drugs or toxins, and 5 had congenital heart disease. The plasma-antigen profile of PAH revealed increased levels of several novel biomarkers, including EPO. Immune quantitative and histochemical studies revealed that EPO not only was significantly elevated in the plasma of PAH patients but also promoted pulmonary artery endothelial cell network formation and smooth muscle cell proliferation. MAP is a hypothesis-generating approach to identifying novel pathophysiologic pathways in PAH. EPO is upregulated in the circulation and lungs of patients with PAH and may affect endothelial and smooth muscle cell proliferation. PMID:25006446

  3. PULMONARY ARTERIAL HYPERTENSION IN ISOLATED PORTAL VEIN DISEASE MAY DIFFER FROM OTHER FORMS OF PORTOPULMONARY HYPERTENSION

    OpenAIRE

    Marcela Tavačová; Milan Luknár; Iveta Šimková; Peter Lesný; Eva Goncalvesová

    2013-01-01

    Portopulmonary hypertension (POPH) is associated with a poor prognosis in comparison to some other types of pulmonary arterial hypertension (PAH). Due to various causes of portal hypertension, the subgroup of POPH can be heterogeneous and PAH is considered to be related more closely to portal hypertension than to an intrinsic hepatic disorder. We report a retrospective series of 4 consecutive patients with severe POPH due to pre-hepatic portal hypertension and no signs of liver function impai...

  4. Sildenafil in pediatric pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    A K Dhariwal

    2015-01-01

    Full Text Available 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.

  5. [Pulmonary arterial hypertension: changing approaches to management].

    Science.gov (United States)

    Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N

    2011-01-01

    The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used. PMID:21626809

  6. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    OpenAIRE

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

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of ...

  7. 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...

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

    OpenAIRE

    Mulder, B. J. M.

    2010-01-01

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

  9. Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension

    OpenAIRE

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

    2015-01-01

    Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December ...

  10. Pharmacotherapeutic management of pulmonary arterial hypertension.

    Science.gov (United States)

    Anderson, Joe R; Nawarskas, James J

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a disabling chronic disorder of the pulmonary vasculature, which is characterized by increased pulmonary artery pressure as a result of increased pulmonary vascular resistance. The pathology of PAH is characterized by pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. These changes are a result of an imbalance between vasodilators (prostacyclin, nitric oxide, vasoactive intestinal peptide) and vasoconstrictors (thromboxane A2, endothelin, serotonin), growth inhibitors and mitogenic factors, and antithrombotic and prothrombotic factors. Recent advances in treatment are directed at restoring the balance between these systems. Endothelin receptor antagonists (bosentan, ambrisentan, sitaxsentan), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil), and prostacylin (epoprostenol, iloprost, treprostinil, beraprost) represent the different classes of medications that are currently used in monotherapy and in combination to treat PAH. The purpose of this drug highlight is to provide the reader with an update of the pharmacotherapeutic treatment of PAH. PMID:20395700

  11. 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.

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

    Science.gov (United States)

    Humbert, M

    2010-03-01

    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. PMID:20956167

  13. Update on pulmonary arterial hypertension pharmacotherapy.

    Science.gov (United States)

    Velayati, Arash; Valerio, Marcos G; Shen, Michael; Tariq, Sohaib; Lanier, Gregg M; Aronow, Wilbert S

    2016-06-01

    Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs. PMID:27232660

  14. Changes in Large Pulmonary Arterial Viscoelasticity in Chronic Pulmonary Hypertension

    OpenAIRE

    Wang, Zhijie; Lakes, Roderic S.; Golob, Mark; Eickhoff, Jens C.; Chesler, Naomi C.

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent change...

  15. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2009-01-01

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

  16. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2016-01-01

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

  17. [Treatment algorithm for pulmonary arterial hypertension].

    Science.gov (United States)

    Hoeper, Marius M

    2005-06-01

    During the last decade, we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids including subcutaneous treprostinil and inhaled iloprost also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for PAH. Novel endothelin receptor antagonists such as sitaxsentan and ambrisentan are currently being investigated. The phosphodiesterase type 5 inhibitor sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other phosphodiesterase type 5 inhibitors have not yet undergone extensive study in PAH. However, PAH is a complex disorder and targeting a single pathway cannot be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, hemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomized clinical trials.Based on the available data, several guidelines for the diagnostic and therapeutic approach to PAH have been published recently. These guidelines have incorporated treatment algorithms, which, fortunately, are virtually identical. The present review article summarizes the current guidelines to the management of patients with PAH. PMID:15965810

  18. Phase I safety study of ranolazine in pulmonary arterial hypertension

    OpenAIRE

    Gomberg-Maitland, Mardi; Schilz, Robert; Mediratta, Anuj; Addetia, Karima; Coslet, Sandra; Thomeas, Vasiliki; Gillies, Hunter; Oudiz, Ronald J

    2015-01-01

    Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swa...

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

    OpenAIRE

    Gérald Simonneau; Laurent Savale; Andrei Seferian; David Montani; Marc Humbert

    2013-01-01

    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...

  20. Types of Pulmonary Hypertension

    Science.gov (United States)

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  1. 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. ... All Open All Close All Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  2. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed; Erzurum, Serpil C; Aldred, Micheala A

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  3. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    Directory of Open Access Journals (Sweden)

    Samar Farha

    Full Text Available Pulmonary arterial hypertension (PAH is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA, which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls and N = 46 African Americans (13 PAH and 33 controls]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3 (all p ≤ 0.05. Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa.

  4. 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 of...

  5. Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials

    OpenAIRE

    Kuwana, Masataka; Watanabe, Hiroshi; Matsuoka, Nobushige; Sugiyama, Naonobu

    2013-01-01

    Objectives Few studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established. Design Meta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and ...

  6. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Korsholm, Kasper; 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...... with idiopathic PAH, heritable PAH, connective tissue disease, HIV infection, and portal hypertension. In conclusion, survival rates in the Danish PAH population were similar to or slightly better than survival rates estimated in other modern registries. However, PAH remains a fatal disease, despite...

  8. Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension

    OpenAIRE

    Hirashiki, Akihiro; Adachi, Shiro; Nakano, Yoshihisa; Kamimura, Yoshihiro; Shimokata, Shigetake; Takeshita, Kyosuke; Murohara, Toyoaki; Kondo, Takahisa

    2016-01-01

    Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 ...

  9. 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 ...

  10. Medical therapies for pulmonary arterial hypertension.

    Science.gov (United States)

    Pulido, Tomas; Zayas, Nayeli; de Mendieta, Maitane Alonso; Plascencia, Karen; Escobar, Jennifer

    2016-05-01

    Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure. PMID:26791159

  11. The right ventricle in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Robert Naeije

    2014-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a right heart failure syndrome. In early-stage PAH, the right ventricle tends to remain adapted to afterload with increased contractility and little or no increase in right heart chamber dimensions. However, less than optimal right ventricular (RV–arterial coupling may already cause a decreased aerobic exercise capacity by limiting maximum cardiac output. In more advanced stages, RV systolic function cannot remain matched to afterload and dilatation of the right heart chamber progressively develops. In addition, diastolic dysfunction occurs due to myocardial fibrosis and sarcomeric stiffening. All these changes lead to limitation of RV flow output, increased right-sided filling pressures and under-filling of the left ventricle, with eventual decrease in systemic blood pressure and altered systolic ventricular interaction. These pathophysiological changes account for exertional dyspnoea and systemic venous congestion typical of PAH. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterisation measurements. Treatment of RV failure in PAH relies on: decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimise ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. To date, there has been no report of the efficacy of drug treatments that specifically target the right ventricle.

  12. Endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  13. Pulmonary arterial hypertension: Advances in pathophysiology and management

    OpenAIRE

    Sandeep Chopra; Dinesh K Badyal; P Chris Baby; Davis Cherian

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous, hemodynamic, and pathophysiological state which is commonly found throughout the world, but the disease burden is greater in India and in other developing countries. It is a disease characterized by vascular obstruction and vasoconstriction leading to progressive increase in pulmonary vascular resistance and right ventricular failure. PAH is a progressive disorder carrying a poor prognosis; however, dramatic progress has occurred in ou...

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

    OpenAIRE

    Barst, Robyn J.

    2007-01-01

    Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ETA] and/or type-B [ETB]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ETA-selecti...

  15. Pulmonary arterial hypertension: on the way to a manageable disease.

    Science.gov (United States)

    Mucke, Hermann A M

    2008-09-01

    Pulmonary arterial hypertension (PAH) is an orphan disease for which no specific pharmacological therapy was available until 1996. Pharmacotherapy for PAH is currently dominated by three endothelin receptor antagonists, bosentan, ambrisentan and sitaxentan (which is not yet approved in the US), and the PDE5 inhibitor sildenafil. Drug candidates undergoing phase III clinical trials for PAH include inhalable and oral treprostinil, aviptadil (an inhalable vasoactive intestinal peptide), and the PDE5 inhibitor tadalafil. Riociguat, a soluble guanylate cyclase stimulator, is scheduled to enter phase III clinical trials in 2008. By approximately 2010, the role of infusable or injectable PGs as treatment for PAH will likely diminish significantly, while inhalable nitric oxide will remain as mainstay therapy in neonatal PAH. Benefits in survival and quality-of-life will decide if any of the more experimental approaches that utilize newly discovered molecular pathways in PAH will ultimately result in marketed drugs. PMID:18729002

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

    OpenAIRE

    Cha Gon Lee; Su In Jeong; June Huh; I-Seok Kang; Heung Jae Lee; Ji-Hyuk Yang; Tae Gook Jun

    2010-01-01

    Purpose : Despite recent advances in pulmonary hypertension management and surgery, appropriate guidelines remain to be developed for operability in congenital heart disease with pulmonary artery hypertension (PAH). Our aim was to evaluate clinical outcomes of patients with severe PAH who underwent surgical closure of left-to-right shunt lesions (LRSL) on the basis of pulmonary reactivity. Methods : We retrospectively reviewed 21 patients who underwent surgical closure of LRSL with severe PAH...

  17. 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.

  18. Pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

    Science.gov (United States)

    Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B

    2013-01-01

    Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary

  19. Pulmonary Arterial Hypertension Associated with Congenital Heart Disease and Eisenmenger Syndrome: Current Practice in Pediatrics

    OpenAIRE

    Frank, David B.; Hanna, Brian D.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an uncommon but serious disease characterized by severe pulmonary vascular disease and significant morbidity and mortality. PAH associated with congenital heart disease (APAH-CHD) is one etiology of PAH that has innate characteristics delineating it from other forms of PAH. The patient with APAH-CHD presents with unique challenges consisting of not only pulmonary vascular disease but also the complexity of the cardiac lesion. Eisenmenger syndrome (ES) ...

  20. Understanding the impact of pulmonary arterial hypertension on patients' and carers' lives

    OpenAIRE

    Loïc Guillevin; Iain Armstrong; Rino Aldrighetti; Howard, Luke S.; Henrik Ryftenius; Aryeh Fischer; Sandra Lombardi; Sean Studer; Pisana Ferrari

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a rare, debilitating and rapidly progressive disease. Although there have been important medical advances in PAH management, the search for a cure continues. Despite an increased understanding of the disease, data on the wider effect of PAH on patients and carers, beyond the clinical symptoms, are still limited. In order to explore this, a large-scale international survey investigated four key areas affected by PAH (physical and practical, emotional, s...

  1. Sildenafil versus nitric oxide for acute vasodilator testing in pulmonary arterial hypertension

    OpenAIRE

    Milger, Katrin; Felix, Janine F.; Voswinckel, Robert; Sommer, Natascha; Franco, Oscar H; Grimminger, Friedrich; Reichenberger, Frank; Seeger, Werner; Ghofrani, Hossein A; Gall, Henning

    2015-01-01

    Vasoreactivity testing with inhaled NO is recommended for pulmonary arterial hypertension (PAH) because of its therapeutic and prognostic value. Sildenafil has acute pulmonary vasodilating properties, but its diagnostic and prognostic impact in PAH is unknown. Our objective was to compare acute vasodilating responses to sildenafil and those to NO during right heart catheterization and also their prognostic values in patients with PAH. Ninety-nine patients with idiopathic PAH and 99 with assoc...

  2. Clinical Safety, Pharmacokinetics, and Efficacy of Ambrisentan Therapy in Children With Pulmonary Arterial Hypertension

    OpenAIRE

    Takatsuki, Shinichi; Rosenzweig, Erika B; Zuckerman, Warren; Brady, Daniela; Calderbank, Michelle; Ivy, D. Dunbar

    2012-01-01

    Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan ...

  3. Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management

    OpenAIRE

    Denton, C P; Hachulla, E

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening complication of systemic sclerosis (SSc). However, PAH-specific treatments are available and can significantly improve survival of patients, especially those diagnosed in World Health Organization (WHO) functional class (FC) II. Registry data have shown that without screening, more than two-thirds of PAH-SSc patients are in WHO FC III or IV when diagnosed. The recognised predisposition of SSc patients to develop PAH should mean that ...

  4. [Pulmonary arterial hypertension associated with connective tissue diseases].

    Science.gov (United States)

    Legendre, Paul; Mouthon, Luc

    2014-09-01

    Pulmonary arterial hypertension (PAH) is a classical complication of connective tissue diseases (CTD), particularly in systemic sclerosis (SSc), systemic lupus erythematous (SLE) or mixed connective tissue diseases (MCTD). The prevalence of PAH in SSc, as measured by right heart catheterization (RHC), is estimated between 7.85 to 13%. The detection of PAH in SSc is based on trans-thoracic echocardiography. Early detection in pulmonary hypertension is the best way to improve the survival in these diseases. In the DETECT study, 19% of high-risk PAH patients with SSc (SSc diagnosed less than 3 years before and DLcodiversification of treatments available, but remains reserved. Therapeutic combinations and new molecules should allow to improve the prognosis. PMID:25129118

  5. Looking to the future: a new decade of pulmonary arterial hypertension therapy

    OpenAIRE

    V.V. McLaughlin

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a severe and debilitating disease characterised by vascular proliferation and remodelling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance, increased afterload on the right ventricle and, ultimately, right heart failure. Although there is no “cure” for PAH, the availability of targeted therapies over the past decade has led to major advances in the management of PAH, reflected in improvements in surviv...

  6. Leptin levels predict survival in pulmonary arterial hypertension

    OpenAIRE

    Tonelli, Adriano R.; Aytekin, Metin; Ariel E Feldstein; Dweik, Raed A

    2012-01-01

    Evidence suggests that leptin is involved in relevant processes in the cardiovascular system. Low serum leptin levels have been associated with increased cardiovascular events and mortality in patients with coronary artery, diabetes, or chronic kidney disease. We hypothesized that leptin is increased in pulmonary arterial hypertension (PAH) and provides prognostic information. We correlated leptin levels with clinical data and assessed its association with survival. Sixty-seven patients with ...

  7. Prostanoid therapies in the management of pulmonary arterial hypertension

    OpenAIRE

    LeVarge, Barbara

    2015-01-01

    Barbara L LeVarge Department of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated ...

  8. 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.

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

    Science.gov (United States)

    Wang, Zhijie; Lakes, Roderic S; Golob, Mark; Eickhoff, Jens C; Chesler, Naomi C

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

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

    Science.gov (United States)

    Montani, David; Seferian, Andrei; Savale, Laurent; Simonneau, Gérald; Humbert, Marc

    2013-09-01

    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. PMID:23997051

  11. 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.

  12. Treatment of pulmonary arterial hypertension in connective tissue disease.

    Science.gov (United States)

    Grünig, Ekkehard

    2012-05-28

    Pulmonary arterial hypertension (PAH) is a group of distinct disorders that includes idiopathic PAH (IPAH), familial PAH and PAH associated with other conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital heart disease. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance. If left untreated, PAH can lead to right heart failure and premature death. CTD-APAH represents an important clinical subgroup of APAH that has a higher risk of death than IPAH. The European treatment guidelines advocate the use of PAH-targeted therapies including bosentan, ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A recommendations), tadalafil or treprostinil (I-B recommendations) for patients in WHO functional class II-III. Not all randomized clinical studies of the approved PAH-targeted therapies have included patients with CTD-APAH. The purpose of this review is to describe the clinical characteristics of CTD-APAH and discuss the approved pharmacological treatments, with a focus on data specific to this subgroup where possible. PMID:22621693

  13. [Combination treatment in pulmonary arterial hypertension].

    Science.gov (United States)

    Kramer, Mordechai R

    2011-04-01

    In recent years, there has been a marked improvement in the treatment of pulmonary arterial hypertension (PAH) due to the development of targeted therapies. There are now several treatment options available--oral, inhaled, and those delivered by subcutaneous or intravenous methods. These treatments have greatly improved patient survival, which in the past was 2.5 years on average. Efficient treatment choice generally proceeds from oral therapies--PDE-5 inhibitors (sildenafil) and endothelin receptor antagonists (bosentan or ambrisentan)--to inhaled prostanoids (iloprost) or subcutaneous (treprostinil). Intravenous prostacyclins are used in treating the more severe cases. The different pathways of action of each class of drugs allow a synergistic effect of combination therapy similar to malignancy or patients in congestive heart failure. The updated treatment algorithm includes combinations of therapies that target different pathways. This article will review the literature regarding combination therapy for the treatment of PAH. Combining PAH therapies that target different pathways is now a well-established treatment option, based on numerous international clinical trials, and offers new hope to patients suffering from this severe disease. PMID:22164922

  14. 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

  15. Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

    OpenAIRE

    Kadriye Kılıçkesmez; M. Serdar Küçükoğlu

    2010-01-01

    The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and he...

  16. The limits of oral therapy in pulmonary arterial hypertension management.

    Science.gov (United States)

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  17. 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.

  18. Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.

    Science.gov (United States)

    Clarke, Megan; Walter, Claire; Agarwal, Richa; Kanwar, Manreet; Benza, Raymond L

    2014-07-01

    The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class. PMID:24851934

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

    Science.gov (United States)

    Delcroix, M; Naeije, R

    2010-09-01

    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. PMID:20956193

  20. 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.

  1. 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. PMID:26730462

  2. The limits of oral therapy in pulmonary arterial hypertension management

    Directory of Open Access Journals (Sweden)

    Liu QQ

    2015-11-01

    Full Text Available Qian-Qian Liu,1,2 Zhi-Cheng Jing1,3 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Echocardiography, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Pulmonary arterial hypertension (PAH is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. Keywords: pulmonary arterial hypertension, right heart failure, oral therapy, survival

  3. 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

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

    OpenAIRE

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

    2015-01-01

    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 rev...

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

    OpenAIRE

    Galiè, N.; Sitbon, O

    2010-01-01

    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 Organizat...

  6. New mechanisms of pulmonary arterial hypertension: role of Ca2+ signaling

    OpenAIRE

    Kuhr, Frank K.; Smith, Kimberly A; Song, Michael Y.; Levitan, Irena; Yuan, Jason X-J

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a severe and progressive disease that usually culminates in right heart failure and death if left untreated. Although there have been substantial improvements in our understanding and significant advances in the management of this disease, there is a grim prognosis for patients in the advanced stages of PAH. A major cause of PAH is increased pulmonary vascular resistance, which results from sustained vasoconstriction, excessive pulmonary vascular remod...

  7. Cost effectiveness of first-line oral therapies for pulmonary arterial hypertension: A modelling study

    OpenAIRE

    Coyle, K.; Coyle, D.; Blouin, J.; Lee, K; Jabr, MF; Tran, K.; Mielniczuk, L; Swiston, J; Innes, M.

    2016-01-01

    Background: In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective: The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods: A cost-utility ...

  8. Cost Effectiveness of First-Line Oral Therapies for Pulmonary Arterial Hypertension: A Modelling Study

    OpenAIRE

    Coyle, Kathryn; Coyle, Doug; Blouin, Julie; Lee, Karen; Jabr, Mohammed F.; Tran, Khai; Mielniczuk, Lisa; Swiston, John; Innes, Mike

    2016-01-01

    Background In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods A cost-utility ana...

  9. A New Era in Medical Management of Severe Pediatric Pulmonary Arterial Hypertension

    OpenAIRE

    Ivy, Dunbar; Saji, Ben T

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease whose prognosis has changed dramatically over the past decade since the introduction of new therapeutic agents as well as the off-label application of adult pulmonary hypertension specific therapies to children. Nevertheless, PAH still has no cure and the aim of treatment is to prolong survival by improving quality of life, symptoms, exercise capacity and hemodynamics. The selection of appropriate therapies for PH is complex ...

  10. Pulmonary arterial hypertension in children: Diagnostic work-up and challenges

    OpenAIRE

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

    2009-01-01

    The diagnostic evaluation of a pediatric patient with suspected pulmonary arterial hypertension (PAH) is extensive but essential, given the rapid progression of the disease if left undiagnosed and untreated. The major goals of performing a complete diagnostic work-up are to confirm the diagnosis of PAH, assess disease severity, rule out associated diseases, and begin to formulate an individualized treatment plan for the pediatric patient with pulmonary hypertension. This article will provide ...

  11. New Trial Designs and Potential Therapies for Pulmonary Artery Hypertension

    OpenAIRE

    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.

    2013-01-01

    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 t...

  12. Drug treatment of pulmonary arterial hypertension: current and future agents.

    Science.gov (United States)

    Hoeper, Marius M

    2005-01-01

    During the last decade we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids, including subcutaneous treprostinil and inhaled iloprost, also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for patients with PAH in functional class III. Novel endothelin receptor antagonists such as sitaxsentan sodium and ambrisentan are currently being investigated. The PDE5 sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other PDE5 inhibitors have not yet undergone extensive study in PAH. The increasing insight into the pathogenesis of PAH opens several new therapeutic opportunities, which include vasoactive intestinal peptide, selective serotonin reuptake inhibitors, adrenomedullin and HMG-CoA reductase inhibitors (statins). However, PAH is a complex disorder and targeting a single pathway can not be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, haemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomised clinical trials. PMID:15977967

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

    OpenAIRE

    Prakash Chelladurai; Werner Seeger; Soni Savai Pullamsetti

    2016-01-01

    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. Th...

  14. Pulmonary rehabilitation and exercise in pulmonary arterial hypertension: An underutilized intervention

    OpenAIRE

    Sahni, Sonu; Capozzi, Barbara; Iftikhar, Asma; Sgouras, Vasiliki; Ojrzanowski, Marcin; Talwar, Arunabh

    2015-01-01

    Pulmonary arterial hypertension (PAH) 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. Early thought process was that exercise and increased physical activity may be detrimental to PAH patients however many small cohort trials have proven otherwise. In addition to the many pharmaceutical options, exercise and pulmonary rehabilitation have also...

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

    OpenAIRE

    Farha Samar; Laskowski Daniel; George Deepa; Park Margaret M; Tang WH Wilson; Dweik Raed A; Erzurum Serpil C

    2013-01-01

    Abstract 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 c...

  16. Evidence for cell fusion is absent in vascular lesions associated with pulmonary arterial hypertension

    OpenAIRE

    Majka, S. M.; M. Skokan; Wheeler, L; Harral, J.; Gladson, S.; Burnham, E.; J. E. Loyd; Stenmark, K R; Varella-Garcia, M; West, J.

    2008-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease associated with severe remodeling of the large and small pulmonary arteries. Increased accumulation of inflammatory cells and apoptosis-resistant cells are contributing factors. Proliferative apoptosis-resistant cells expressing CD133 are increased in the circulation of PAH patients. Circulating cells can contribute to tissue repair via cell fusion and heterokaryon formation. We therefore hypothesized that in the presence of increased l...

  17. Sitaxentan for the Oral Treatment of Pulmonary Arterial Hypertension: Benefits from Endothelin Receptor Subtype Selectivity?

    OpenAIRE

    Hermann A.M. Mucke

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a deadly and underdiagnosed disease which causes right heart failure secondary to pressure overload resulting from the thickening of the pulmonary artery endothelium, associated with elevated levels of circulating endothelin-1. Sitaxentan was the first endothelin antagonist with high selectivity for receptor subtype A (over subtype ET-B) to gain regulatory approval for the treatment of PAH in major pharmaceutical markets. This review traces the develop...

  18. 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. PMID:22790921

  19. Initial dual oral combination therapy in pulmonary arterial hypertension.

    Science.gov (United States)

    Sitbon, Olivier; Sattler, Caroline; Bertoletti, Laurent; Savale, Laurent; Cottin, Vincent; Jaïs, Xavier; De Groote, Pascal; Chaouat, Ari; Chabannes, Céline; Bergot, Emmanuel; Bouvaist, Hélène; Dauphin, Claire; Bourdin, Arnaud; Bauer, Fabrice; Montani, David; Humbert, Marc; Simonneau, Gérald

    2016-06-01

    Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. PMID:26989105

  20. Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Ma, Zhiyuan; Mao, Lan; Rajagopal, Sudarshan

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed. PMID:27167679

  1. 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.

  2. Hypertensive encephalopathy complicating transplant renal artery stenosis.

    OpenAIRE

    McGonigle, R J; Bewick, M.; Trafford, J. A.; Parsons, V

    1984-01-01

    A 26-year-old female diabetic patient developed hypertensive encephalopathy with gross neurological abnormalities complicating renal artery stenosis of her transplant kidney. The elevated blood pressure was unresponsive to medical treatment. Surgical correction of the stenoses in the renal artery cured the hypertension and renal failure and led to the patient's complete recovery.

  3. 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.

  4. 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.

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

    OpenAIRE

    Adel Boueiz; Hassoun, Paul M.

    2014-01-01

    The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines. Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases,...

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

    Science.gov (United States)

    Papathanasiou, Athanasios; Nakos, George

    2015-11-01

    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

  7. What Causes Pulmonary Hypertension?

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... different types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the ...

  8. 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......, 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 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...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Antonio Lopes

    2014-01-01

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

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

    Science.gov (United States)

    Barst, Robyn J

    2007-01-01

    Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ET(A)] and/or type-B [ET(B)]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ET(A)-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5-10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ET(A)/ET(B) ERA, bosentan, and the ET(A)-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH. PMID:17583171

  12. Peptide-Coated Liposomal Fasudil Enhances Site Specific Vasodilation in Pulmonary Arterial Hypertension

    OpenAIRE

    Nahar, Kamrun; Absar, Shahriar; Gupta, Nilesh; Kotamraju, Venkata Ramana; McMurtry, Ivan F.; Oka, Masahiko; Komatsu, Masanobu; Nozik-Grayck, Eva; Ahsan, Fakhrul

    2014-01-01

    This study sought to develop a liposomal delivery system of fasudil—an investigational drug for the treatment of pulmonary arterial hypertension (PAH)—that will preferentially accumulate in the PAH lungs. Liposomal fasudil was prepared by film-hydration method, and the drug was encapsulated by active loading. The liposome surface was coated with a targeting moiety, CARSKNKDC, a cyclic peptide; the liposomes were characterized for size, polydispersity index, zeta potential, and storage and neb...

  13. Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency

    OpenAIRE

    Ruiter, Gerrina; Manders, Emmy; Happé, Chris M.; Schalij, Ingrid; Groepenhoff, Herman; Howard, Luke S.; Wilkins, Martin R.; Bogaard, Harm J.; Westerhof, Nico; van der Laarse, Willem J.; de Man, Frances S.; Vonk-Noordegraaf, Anton

    2015-01-01

    In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (...

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

    OpenAIRE

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

    2013-01-01

    Pulmonary arterial hypertension (PAH) remains a life-limiting condition with a major impact on the ability to lead a normal life. Although existing therapies may improve the outlook in some patients there remains a major unmet need to develop more effective therapies in this condition. There have been significant advances in our understanding of the genetic, cell and molecular basis of PAH over the last few years. This research has identified important new targets that could be explored as po...

  15. Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?

    OpenAIRE

    Opitz, Christian F; Ewert, Ralf; Kirch, Wilhelm; Pittrow, David

    2008-01-01

    Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ETA and ETB), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongo...

  16. Safety and tolerability of bosentan in the management of pulmonary arterial hypertension

    OpenAIRE

    Preston, Ioana

    2009-01-01

    Kari E Roberts, Ioana R PrestonPulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothe...

  17. [Pulmonary hypertension and right ventricular failure. Part XI. Endothelin receptor blockers in the treatment of primary pulmonary arterial hypertension].

    Science.gov (United States)

    Batyraliev, T A; Makhmutkhodzhaev, S A; Ekinsi, E; Pataraia, S A; Pershukov, I V; Sidorenko, B A; Preobrazhenskiĭ, D V

    2007-01-01

    In a series of articles the authors discuss literature data concerning epidemiology of pulmonary arterial hypertension (PAH), its current classification; peculiarities of its pathogenesis and treatment in various diseases and conditions. In the eleventh communication the authors discuss literature data related to the role of endothelin system in pathogenesis of primary (idiopathic) PAH, as well as PAH associated with diffuse diseases of connective tissue and congenital heart disease. This communication also contains presentation of clinical pharmacology of three available endothelin receptor blockers - bosentan, sitaxsentan, ambrisentan, and analysis of results of randomized controlled trials of efficacy and safety of these agents in patients with idiopathic PAH and PAH associated with diffuse diseases of connective tissue and congenital heart disease. PMID:18260899

  18. 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

  19. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension.

    Science.gov (United States)

    Yamamura, Aya

    2014-01-01

    Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. PMID:24770445

  20. A Dosing/Cross-Development Study of the Multikinase Inhibitor Sorafenib in Patients With Pulmonary Arterial Hypertension

    OpenAIRE

    Gomberg-Maitland, M.; Maitland, ML; Barst, RJ; Sugeng, L; Coslet, S; Perrino, TJ; Bond, L.; LaCouture, ME; Archer, SL; Ratain, MJ

    2009-01-01

    Pulmonary arterial hypertension (PAH) and cancer share elements of pathophysiology. This provides an opportunity for the cross-development of anticancer agents that can be used in improving PAH care. The adaptation of new drugs across these disease populations warrants a structured approach. This study was a 16-week, phase Ib, single-center, open-label trial of the multikinase/angiogenesis inhibitor sorafenib. In order to assess the safety of sorafenib in PAH, patients with advanced but stabl...

  1. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study

    OpenAIRE

    Khan, Sadiya S.; Cuttica, Michael J.; Beussink-Nelson, Lauren; Kozyleva, Anastasia; Sanchez, Cynthia; Mkrdichian, Hamorabi; Selvaraj, Senthil; Dematte, Jane E.; Daniel C. Lee; Shah, Sanjiv J.

    2015-01-01

    Ranolazine, a late inward sodium current and fatty acid oxidation inhibitor, may improve right ventricular (RV) function in pulmonary arterial hypertension (PAH); however, the safety and efficacy of ranolazine in humans with PAH is unknown. Therefore, we sought to (1) determine whether ranolazine is safe and well tolerated in PAH and (2) explore ranolazine’s effect on symptoms, exercise capacity, RV structure and function, and hemodynamic characteristics. We therefore conducted a 3-month, pro...

  2. 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.

  3. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Fukuda, Yutaka; Momoi, Nobuo; Akaihata, Mitsuko; Nagasawa, Katsutoshi; Mitomo, Masaki; Aoyagi, Yoshimichi; Endoh, Kisei; Hosoya, Mitsuaki

    2015-08-01

    Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists. PMID:25809637

  4. Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension

    Science.gov (United States)

    Adachi, Shiro; Nakano, Yoshihisa; Kamimura, Yoshihiro; Shimokata, Shigetake; Takeshita, Kyosuke; Murohara, Toyoaki; Kondo, Takahisa

    2016-01-01

    Abstract Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% ± 2.42% at baseline to 8.07% ± 3.18% after 3 months (P FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = −0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity. PMID:27252842

  5. 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.)

  6. Oral Therapies for the Treatment of Pulmonary Arterial Hypertension: A Population-Based Cost-Minimization Analysis

    OpenAIRE

    George Dranitsaris; Sanjay Mehta

    2009-01-01

    Background and objective:Background and objective: Pulmonary arterial hypertension (PAH) is a rare but life-threatening condition that is characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right-sided heart failure and frequently death. Orally administered agents used for the treatment of symptomatic, moderate-to-severe PAH include sildenafil and the endothelin (ET) receptor antagonists (ERAs), bosentan and sitaxentan (sitaxsentan...

  7. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  8. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Jane A. Leopold

    2016-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype.

  9. Characteristics of arterial hypertension in obesity

    Directory of Open Access Journals (Sweden)

    Ivković-Lazar Tatjana A.

    2004-01-01

    Full Text Available Introduction Arterial hypertension is the most frequent cardiovascular disease in obese persons, progressing with time to left ventricular hypertension, often associated with dilatation, diastolic disorders, hearth rhythm disturbance, and generalized atherosclerosis. Etiology The origin of this disease is related to hemodynamic disturbances (increased blood volume, minute volume, mainly due to increased stroke volume accompanied with changes of peripheral resistance, which increases in a later phase. However, metabolic factors are presently considered as primarily responsible for appearance of hypertension, which has rightly obtained the attribute of metabolic hypertension. A key role belongs to insulin, in fact, to insulin resistance and hyperinsulinism. Treatment Awareness of the metabolic basis of arterial hypertension in obesity has resulted in a specific approach to its treatment. The primary treatment includes reduction diet, with a drastic reduction of salt intake and with compulsory physical activity, while concerning medications one should consider converting enzyme inhibitors, alpha1 blockers and calcium channel antagonists. .

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

    Science.gov (United States)

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

    2014-07-18

    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 attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rβ phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH. PMID:24950404

  11. Pulmonary arterial hypertension: Advances in pathophysiology and management

    Directory of Open Access Journals (Sweden)

    Sandeep Chopra

    2012-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is a heterogeneous, hemodynamic, and pathophysiological state which is commonly found throughout the world, but the disease burden is greater in India and in other developing countries. It is a disease characterized by vascular obstruction and vasoconstriction leading to progressive increase in pulmonary vascular resistance and right ventricular failure. PAH is a progressive disorder carrying a poor prognosis; however, dramatic progress has occurred in our knowledge of its pathogenesis and consequently, its treatment over the last two decades. In this article, we attempt to provide an overview of the etiology, pathophysiology, and current therapeutic modalities in the treatment of PAH. Patients suspected to have PAH should be submitted to a battery of investigations which help in establishing the diagnosis, identifying the etiology, guiding in treatment and informing the prognosis. All patients should be considered for standard therapy with oxygen, anticoagulation, and diuretics for right heart failure. Oral calcium channel blockers should be used in patients with a favorable response to acute vasodilator challenge. Disease targeted therapies include prostacyclines, endothelin receptor blockers, and phosphodiesterase-5 inhibitors. A brief mention of new and potential therapeutic strategies is also included.

  12. Ambrisentan for the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Brian Casserly

    2008-12-01

    Full Text Available Brian Casserly1,3, James R Klinger2,31Division of Pulmonary Medicine, The Memorial Hospital of Rhode Island, Pawtucket, RI, USA; 2Division of Pulmonary Sleep and Critical Care Medicine, Rhode Island Hospital; 3Waren Alpert Medical School of Brown University, Providence, RI, USAAbstract: Ambrisentan is an endothelin receptor antagonist (ERA that was recently approved for treatment of pulmonary arterial hypertension (PAH. Endothelin (ET is a potent vasoconstrictor with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. The biologic effects of ET are mediated by 2 cell surface receptors termed ETA and ETB. ETA mediates the vasoconstrictor effect of ET on vascular smooth muscle, whereas ETB is expressed primarily on vascular endothelial cells where it induces nitric oxide synthesis and acts to clear ET from the circulation. Ambrisentan is the first ETA selective ERA approved for use in the US. Recently published clinical trials in patients with PAH demonstrate improvement in functional capacity and pulmonary hemodynamics similar to other ETA selective and non-selective ERAs. Its once daily dosing and lower incidence of serum aminotransferase elevation offer potential advantages over other ERAs, but further experience with this agent is needed to fully understand its long-term efficacy and safety. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases. It also examines the development process, safety profile and clinical trials that have resulted in ambrisentan being approved for treatment of PAH.Keywords: ambrisentan, endothelin receptor antagonist, pulmonary hypertension, endothelin

  13. 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

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    Ramani, Gautam V.; Park, Myung H.

    2010-01-01

    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 ba...

  16. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?

    OpenAIRE

    Andrei Seferian; Gérald Simonneau

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the adm...

  17. 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

  18. 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. PMID:27057843

  19. 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

  20. 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.

  1. 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.

  2. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    Science.gov (United States)

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH. PMID:25490411

  3. Expert opinion on available options treating pulmonary arterial hypertension.

    Science.gov (United States)

    Naeije, Robert; Huez, Sandrine

    2007-10-01

    Until in the early nineties, pulmonary arterial hypertension (PAH) was a uniformly fatal disease, with a median life expectancy of approximately 2.5 years. Uncontrolled studies showed that a small proportion of patients responded to high-dose calcium channel blockers, retrospective studies supported the use of anticoagulant therapy and heart-lung or lung transplantation remained the only option. In 1996, a 3-month randomised, placebo-controlled trial showed that chronic intravenous epoprostenol (synthetic prostacyclin) improved functional state, exercise capacity, haemodynamics, and even survival in patients with idiopathic PAH. Similar benefits were subsequently reported and extended to all PAH categories, and confirmed with more stable prostacyclin analogues administered subcutaneously (treprostinil), by inhalation (iloprost), or even orally (beraprost). In the early 2000s, two randomised controlled trials showed efficacy of the oral intake of the dual endothelin A/B receptor antagonist bosentan. Two selective endothelin-A receptor antagonists, sitaxsentan and ambrisentan, are being developed. Finally, a randomised controlled trial has established the therapeutic efficacy of phosphodiesterase-5 inhibition with sildenafil, introducing a third signalling pathway to be targeted by the pharmacological treatment of PAH. Another phosphodiesterase-5 inhibitor, tadalafil, is already being evaluated. While all these treatments have markedly improved the lives of PAH patients, they have not offered yet a cure of the disease. Multi-drug approaches are now under evaluation, with more ambitious therapeutic goals. Alternative approaches with stem cells, RhoA-Rho-kinase inhibitors, platelet derived growth factor inhibitors and vasoactive intestinal peptides are being considered. PMID:17927481

  4. Efficiency of lazer therapy of patients with arterial hypertension

    OpenAIRE

    Krysyuk, O.; Obrezan, A.; Sinitsyn, I.

    2006-01-01

    The article presents results of investigation of efficiency of laser therapy in patients with arterial hypertension. It has been shown that the treatment with laser therapy have got more intensive effects of correction of subjective, metabolic, hemodynemical and ECG distinctions in patients with arterial hypertension than the treatment without laser therapy. Keywards: arterial hypertension, laser t.herapy.

  5. Isolated Pulmonary Arterial Hypertension-Janus' Faces of Hyperthyroidism

    OpenAIRE

    Kang, Beodeul; Cho, Deok-Kyu; Byun, Ki Hyun; Eun, Lucy Youngmin; Cho, Yun-Hyeong

    2009-01-01

    We describe a 54-year-old woman with isolated pulmonary arterial hypertension accompanied by hyperthyroidism due to Graves' disease. Her pulmonary artery hypertension resolved spontaneously after restoration of euthyroidism. This case suggests that hyperthyroidism should be considered a reversible cause of pulmonary arterial hypertension.

  6. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].

    Science.gov (United States)

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    2015-01-01

    In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively. PMID:26047999

  7. [Pulmonary arterial hypertension: a voyage around the year 2008].

    Science.gov (United States)

    Baloira, Adolfo

    2009-01-01

    There have been spectacular developments in pulmonary arterial hypertension (PAH), both in its treatment and knowledge of its pathogenesis. Several studies have been published throughout 2008 that have contributed to improve these two aspects a little. As regards the pathogenesis, mutations in BMPR2 continue gaining points as fundamental factors in the development of the disease. It has been shown that patients who carry any of them have a more rapid and severe clinical course. There is a relationship between the BMPR2 pathway and inflammation of the pulmonary vascular tree. A new anti-endothelin drug, ambrisentan, has also appeared on the scene this year. With an efficacy comparable to other drugs of its group, the secondary effects appear to be a lot less. An important work has been the demonstration of an improvement in several parameters in functional class II in patients with PAH with bosentan. Results using new combinations, such as sildenafil and epoprostenol, have also been presented. A common type of PAH is that which seems to be associated with thromboembolic disease. Treatment with sildenafil and in some selected cases, percutaneous angioplasty, has obtained favourable responses. Finally, in 2008, two new consensus documents have emerged, one Spanish and the other British, which in the light of current knowledge, give a clearer insight into the management of this serious disease. PMID:19303531

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

    International Nuclear Information System (INIS)

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

  9. Noninvasive identification of left-sided heart failure in a population suspected of pulmonary arterial hypertension.

    Science.gov (United States)

    Jacobs, Wouter; Konings, Thelma C; Heymans, Martijn W; Boonstra, Anco; Bogaard, Harm Jan; van Rossum, Albert C; Vonk Noordegraaf, Anton

    2015-08-01

    Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R(2)=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases. PMID:25837029

  10. 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...

  11. [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. PMID:25322625

  12. Acute Effects of Vardenafil on Pulmonary Artery Responsiveness in Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Edibe Karasu-Minareci

    2012-01-01

    Full Text Available Phosphodiesterase type-5 (PDE-5 inhibitors are novel and important options for the treatment of pulmonary arterial hypertension (PAH. Therefore, we aimed to examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries isolated from rats with monocrotaline- (MCT- induced pulmonary hypertension. MCT (60 mg/kg or its vehicle was administered by a single intraperitoneal injection to 6-week-old male Sprague Dawley rats. Rats were sacrificed 21 days after MCT injection, and the main pulmonary arteries were isolated and then mounted in 20 mL organ baths. Concentration-response curves for vardenafil (10−10–10−5 M were constructed in phenylephrine- (Phe- precontracted rings. PAH caused marked rightward shift in the curves to vardenafil whereas maximal responses were not affected. Inhibition of NO synthase (L-NAME, 10−4 M or guanylyl cyclase (ODQ, 10−5 M caused similar attenuation in responses evoked by vardenafil. Moreover, contraction responses induced by CaCl2 (3×10−5–3×10−2 M were significantly reduced in concentration-dependent manner by vardenafil. In conclusion, vardenafil induced pulmonary vasodilatation via inhibition of extracellular calcium entry in addition to NO-cGMP pathway activation. These results provide evidence that impaired arterial relaxation in PAH can be prevented by vardenafil. Thus, vardenafil represents a valuable therapeutic approach in PAH besides other PDE-5 inhibitors.

  13. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study.

    Science.gov (United States)

    Wu, Ji; Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-10-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery-jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189

  14. 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.

  15. Effectiveness of Spironolactone Plus Ambrisentan for Treatment of Pulmonary Arterial Hypertension (from the [ARIES] Study 1 and 2 Trials)

    OpenAIRE

    Maron, Bradley A.; Waxman, Aaron B.; Opotowsky, Alexander R.; Gillies, Hunter; Blair, Christiana; Aghamohammadzadeh, Reza; Loscalzo, Joseph; Jane A. Leopold

    2013-01-01

    In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor—mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to p...

  16. Evaluation of a New Formulation of Epoprostenol Sodium in Japanese Patients with Pulmonary Arterial Hypertension (EPITOME4)

    OpenAIRE

    Tamura, Yuichi; Ono, Tomohiko; Fukuda, Keiichi; Satoh, Toru; Sasayama, Shigetake

    2013-01-01

    ABSTRACT Introduction Pulmonary arterial hypertension (PAH) is associated with poor prognosis despite significant recent advances in its treatment. An intravenous formulation of epoprostenol sodium containing glycine and mannitol (epoprostenol GM; GlaxoSmithKline, London, UK) is widely used to treat PAH. A new formulation of epoprostenol sodium containing arginine and sucrose excipients (epoprostenol AS; Actelion Pharmaceuticals Japan Ltd., Tokyo, Japan) shows better stability at room tempera...

  17. MiRNA-199a-5p influences pulmonary artery hypertension via downregulating Smad3.

    Science.gov (United States)

    Liu, Yuanhua; Liu, Guanghui; Zhang, Hui; Wang, Jing

    2016-05-13

    MicroRNAs (miRNAs) play important roles in pulmonary artery hypertension (PAH). Recently, it has been reported that miR-199a-5p participates in the progression of chronic obstructive pulmonary disease, ventricular hypertrophy and heart failure. However, the roles of miR-199a-5p in PAH are still unclear. In the present study, miR-199a-5p was investigated in PAH rat models and in human pulmonary artery smooth muscle cells (HPASMCs) and endothelial cells (HPAECs). The expression of miR-199a-5p was significantly increased following PAH induction, and anti-miR-199a-5p could increase the nitric oxide (NO) level and decrease the PAH-induced upregulation of pulmonary artery pressure and right ventricular hypertrophy. Moreover, in HPASMCs and HPAECs, miR-199a-5p overexpression could inhibit the level of NO and promote the concentration of Ca(2+), but anti-miR-199a-5p showed opposite results. Further analysis demonstrated that miR-199a-5p attenuated the expression of Smad3. Importantly, Smad3 was confirmed to be the target gene of miR-199a-5p using dual-luciferase reporter assay. Mechanism analyses revealed that the downregulation of NO and the upregulation of Ca(2+) caused by miR-199a-5p were all reversed by Smad3 overexpression in HPASMCs and HPAECs. Moreover, in PAH model, Smad3, p-Smad3 and Smad4 were all downregulated in lung tissues, and SIS3 (Smad3 inhibitor) could reverse the effects of anti-miR-199a-5p in PAH rats. Our date suggest that miR-199a-5p may function as a regulator of PAH by targeting Smad3, indicating a novel therapeutic strategy for patients with PAH. PMID:27038547

  18. 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. PMID:26111581

  19. 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

  20. 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

  1. Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    M Kathryn Steiner

    2008-07-01

    Full Text Available M Kathryn Steiner1, Ioana R Preston21Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Pulmonary Critical Care and Sleep Division, Department of Medicine, Tufts Medical Center, Boston, MA, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH. Bench to bedside scientific research has shown that endothelin-1 (ET-1 is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs improved exercise capacity, functional status, pulmonary hemodymanics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH.Keywords: ambrisentan, bosentan, endothelin receptor antagonists, pulmonary arterial hypertension, sitaxsentan

  2. Safety and tolerability of bosentan in the management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Kari E Roberts

    2009-03-01

    Full Text Available Kari E Roberts, Ioana R PrestonPulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH. Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1 is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.Keywords: bosentan, endothelin receptor antagonists, pulmonary arterial hypertension 

  3. 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.

  4. Use of pulmonary arterial hypertension–approved therapy in the treatment of non–group 1 pulmonary hypertension at US referral centers

    OpenAIRE

    Trammell, Aaron W.; Pugh, Meredith E.; Newman, John H.; Hemnes, Anna R.; Robbins, Ivan M.

    2015-01-01

    Pulmonary hypertension (PH) is a frequent complication of left heart disease and parenchymal lung disease, and it portends increased mortality. A growing number of medications are approved for the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH). However, they are not well studied in PH of other etiologies (WHO groups 2–5). We sought to assess treatment approaches used by PAH referral centers in this diverse group of patients. We developed a semiquant...

  5. 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...

  6. Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension

    OpenAIRE

    Preston, Ioana

    2008-01-01

    M Kathryn Steiner1, Ioana R Preston21Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Pulmonary Critical Care and Sleep Division, Department of Medicine, Tufts Medical Center, Boston, MA, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary ...

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

    OpenAIRE

    Buckley, Mitchell

    2014-01-01

    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 ...

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

    OpenAIRE

    Buckley MS; Berry AJ; Kazem NH; Patel SA; Librodo PA

    2014-01-01

    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 with...

  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. Amlodipine advantages in arterial hypertension therapy

    OpenAIRE

    V.M.Tsareva; N. J. Hozjainova; M. S. Bezaltynnyh; T.V. Brook; N.A. Borohova; I.E. Koltunov; N.M. Ahmedzhanov

    2008-01-01

    Aim. To study effects of calcium channel blocker, amlodipine on indices of ambulatory blood pressure monitoring (ABPM), heart rate variability, corrected QT-interval and its dispersion, structural and functional heart indices, microcirculation in patients with arterial hypertension (HT).Material andmethods. 48 patients with HT of 1-2 stages were involved in the study. After 2 week wash-out period amlodipine (5-10 mg/day) therapy was started. ABPM, 24 hour electrocardiogram monitoring, echocar...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management

    Directory of Open Access Journals (Sweden)

    C.P. Denton

    2010-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a life-threatening complication of systemic sclerosis (SSc. However, PAH-specific treatments are available and can significantly improve survival of patients, especially those diagnosed in World Health Organization (WHO functional class (FC II. Registry data have shown that without screening, more than two-thirds of PAH-SSc patients are in WHO FC III or IV when diagnosed. The recognised predisposition of SSc patients to develop PAH should mean that an optimal screening programme will enable the early diagnosis of PAH, and provide the opportunity for earlier treatment, in this population. Evidence-based treatment guidelines advocate the use of oral PAH-specific therapies, including bosentan, ambrisentan, sildenafil (I-A recommendation, tadalafil (I-B recommendation and sitaxentan (IIA-C recommendation, for patients in WHO FC II. A randomised, placebo-controlled trial of bosentan in WHO FC II PAH patients, including cases of PAH-SSc, showed improved haemodynamics in actively treated patients and a reduced risk of progression from WHO FC II to FC III. For PAH patients diagnosed in WHO FC III, the treatment goal is to improve to WHO FC II. Data from bosentan trials have shown that nearly one-quarter of patients in WHO FC III at baseline can attain WHO FC II status with monotherapy. Maintenance of PAH-SSc patients in WHO FC II with monotherapy is unrealistic, and sequential goal-directed combination therapy is now becoming an accepted treatment strategy. It is hoped that earlier diagnosis, coupled both with regular assessments to ensure treatment goals are being met and timely, appropriate treatment, will further improve the survival rates of those PAH-SSc patients.

  13. Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis.

    Science.gov (United States)

    McLaughlin, V; Humbert, M; Coghlan, G; Nash, P; Steen, V

    2009-06-01

    Pulmonary arterial hypertension (PAH) is a devastating vascular complication of a number of CTDs. In patients with SSc, PAH has a dramatic impact on prognosis and survival and is the single most common cause of disease-related death.Yearly echocardiographic screening for PAH is recommended in patients with SSc. If suspected, confirmation of PAH diagnosis by right heart catheterization is necessary. Treatment goals for patients with PAH associated with SSc (PAH-SSc) aim to slow disease progression and improve quality of life. Some measures used to gauge the effect of treatment in patients with PAH-SSc remain to be fully validated; the 6-min walk distance, for example, is a simple and reproducible means of assessing exercise capacity, but there exists a need to understand what constitutes a clinically relevant change in this specific patient population. Currently, pharmacological intervention in PAH-SSc may target one or more of three pathophysiological pathways in PAH. The prostacyclin analogue epoprostenol has been shown to improve exercise capacity and haemodynamics in PAH-SSc patients and similar data are available from smaller studies on trepostinil and iloprost. The dual endothelin receptor antagonist bosentan has been shown to improve exercise capacity and haemodynamics in PAH-SSc, and similar data have been obtained in small numbers of patients treated with the endothelin receptor A antagonists sitaxsentan and ambrisentan. Impaired production of nitric oxide may be addressed by inhibiting phosphodiesterase type-5 with sildenafil or possibly tadalafil. Combinations of multiple targeted therapies may be beneficial to this patient population. PMID:19487219

  14. Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.

    Science.gov (United States)

    Hachulla, E; Denton, C P

    2010-12-01

    Pulmonary arterial hypertension (PAH) is a life-threatening complication of systemic sclerosis (SSc). However, PAH-specific treatments are available and can significantly improve survival of patients, especially those diagnosed in World Health Organization (WHO) functional class (FC) II. Registry data have shown that without screening, more than two-thirds of PAH-SSc patients are in WHO FC III or IV when diagnosed. The recognised predisposition of SSc patients to develop PAH should mean that an optimal screening programme will enable the early diagnosis of PAH, and provide the opportunity for earlier treatment, in this population. Evidence-based treatment guidelines advocate the use of oral PAH-specific therapies, including bosentan, ambrisentan, sildenafil (I-A recommendation), tadalafil (I-B recommendation) and sitaxentan (IIA-C recommendation), for patients in WHO FC II. A randomised, placebo-controlled trial of bosentan in WHO FC II PAH patients, including cases of PAH-SSc, showed improved haemodynamics in actively treated patients and a reduced risk of progression from WHO FC II to FC III. For PAH patients diagnosed in WHO FC III, the treatment goal is to improve to WHO FC II. Data from bosentan trials have shown that nearly one-quarter of patients in WHO FC III at baseline can attain WHO FC II status with monotherapy. Maintenance of PAH-SSc patients in WHO FC II with monotherapy is unrealistic, and sequential goal-directed combination therapy is now becoming an accepted treatment strategy. It is hoped that earlier diagnosis, coupled both with regular assessments to ensure treatment goals are being met and timely, appropriate treatment, will further improve the survival rates of those PAH-SSc patients. PMID:21119190

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

    Directory of Open Access Journals (Sweden)

    Gautam V Ramani

    2010-05-01

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

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

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    Paulin Roxane

    2011-09-01

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

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

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    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.

  18. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series).

    Science.gov (United States)

    Fessel, Joshua P; West, James D

    2015-12-01

    Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively. PMID:26697167

  19. How to detect disease progression in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2012-03-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rapidly progressive disease, ultimately leading to right heart failure and death. Accumulating evidence indicates that intervention early in disease progression results in better outcomes than delaying treatment. In this review we will discuss the assessments and strategies that can be used to monitor disease progression and guide clinical management. Many tools, such as symptoms, functional classification, exercise capacity, haemodynamic measures, findings on cardiac imaging and levels of biomarkers, have shown to be prognostic for survival both at diagnosis and during treatment. However, attempts to define goal thresholds have produced a variety of results. Several groups have developed risk calculators to estimate individual patients' mortality risk, but the accuracy of these tools across different patient populations remains unknown. What is clear is the importance of regularly assessing a range of parameters and then tailoring treatment goals to each patient. In addition, the use of a multidisciplinary team approach is crucial in order to support patients through all aspects of managing their condition. There is still an urgent need for prospective collaborative initiatives to assess novel goals and improve treatment strategies that would allow physicians to personalise and optimise clinical management for their patients with PAH.

  20. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

    OpenAIRE

    Lammers, Steven R.; Kao, Phil H.; Qi, H. Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R.; Shandas, Robin

    2008-01-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive ...

  1. Renal artery stent angioplasty for renovascular hypertension

    International Nuclear Information System (INIS)

    Objective: To evaluate the therapeutic results of expandable stent for treatment of atherosclerotic renovascular obstructive disease. Methods: 15 patients (10 men and 5 women, 41-75 years old; mean age, 52 years) with renal arterial hypertension underwent renal stent angioplasty including renal arterial stenosis 89%(n=13) and fully obstruction without function in 2, of which 2 patients had bilateral involvement. The stenotic range of all arterial segments showed 60% to 90% width of the normal arterial diameter. 16 stents were implanted under the guidance of fluoroscopy. The most of stents implanted were Palmaz (n=12, 75%) with regular clinical and angiographic follow up. Results: Technical success (residual stenosis <30%) was achieved in all patients without serious complication. During the follow-up (6-15 months; mean, 8 ± 4 months), hypertension was improved in 9 patients and cured in 4 patients with a total benefit of 86% and no efficacy in 2(13%). The average systolic blood pressure decreased from 27.12 ± 3.09 kPa to 18.62 ± 3.12 kPa and the average diastolic blood pressure decreased from 17.73 ± 1.92 kPa to 11.12 ± 2.43 kPa after stent treatment (P<0.05). Serum creatinine remained stable in 60% (n=9) patients with improvement in 33% (n=5) and worsened in 6% (n=1) patients. Follow-up angiography was performed in all patients with 1 case of a restenosis. 6 months after expanding through stent by using balloon, the two follow up angiographies showed a stable restenosis about 20%. Conclusions: Percutaneous transluminal stent placement is highly beneficial for patients who had renal arterial obstructive disease. The success of stent angioplasty of complete obstructive renal arteries reveals wide prospects for interventional method. (authors)

  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. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study

    OpenAIRE

    Beghetti, Maurice; Haworth, Sheila G; Bonnet, Damien; Barst, Robyn J.; Acar, Philippe; Fraisse, Alain; Ivy, Dunbar D; Jais, Xavier; Schulze-Neick, Ingram; Galiè, Nazzareno; Morganti, Adele; Dingemanse, Jasper; Kusic-Pajic, Andjela; Berger, Rolf M F

    2009-01-01

    AIM To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation. METHODS Thirty-six paediatric PAH patients were enrolled in this multicentre, prospective, open-label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg−1 b.i.d. and then for 8 weeks with 4 mg kg−1 b.i.d. Blood samples were taken for pharmacokinetic pur...

  4. 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)

  5. The Relationship of Fluid Overload as Assessed by Bioelectrical Impedance Analysis with Pulmonary Arterial Hypertension in Hemodialysis Patients.

    Science.gov (United States)

    Yılmaz, Süreyya; Yildirim, Yasar; Taylan, Mahsuk; Demir, Melike; Yilmaz, Zülfükar; Kara, Ali Veysel; Aydin, Fatma; Sen, Hadice Selimoglu; Karabulut, Aziz; Topcu, Fusun

    2016-01-01

    BACKGROUND Pulmonary arterial hypertension (PAH) is common disease among hemodialysis (HD) patients and is associated with increased morbidity and mortality. However, its pathogenesis has not been completely elucidated. We aimed to evaluate the frequency of PAH in HD patients, as well as the relationship between fluid status and PAH. MATERIAL AND METHODS We enrolled 77 HD patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status. BIA was performed before and 30 min after the midweek of HD. Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Echocardiographic examinations were performed before and after the HD. Pulmonary arterial hypertension was defined as systolic pulmonary artery pressure at rest (sPAP) higher than 35 mmHg. RESULTS PAH was found in 33.7% of the HD patients. OH/ECW and the frequency of fluid overload were significantly higher in HD patients with PAH than those without PAH, whereas serum albumin and hemoglobin levels were significantly lower. sPAP level was significantly higher in HD patients with fluid overload than in those without fluid overload after hemodialysis session. Furthermore, sPAP, OH/ECW levels, and the frequency of PAH were significantly reduced after HD. We also found a significant positive correlation between sPAP and OH/ECW. Multivariate logistic regression analysis demonstrated fluid overload to be an independent predictor of PAH after HD. CONCLUSIONS PAH is prevalent among HD patients. This study demonstrated a strong relationship between fluid overload and PAH in HD patients. PMID:26874785

  6. Increasing pulmonary artery pulsatile flow improves hypoxic pulmonary hypertension in piglets.

    Science.gov (United States)

    Courboulin, Audrey; Kang, Chantal; Baillard, Olivier; Bonnet, Sebastien; Bonnet, Pierre

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH. PMID:25993379

  7. Novel biomarkers for pulmonary arterial hypertension.

    Science.gov (United States)

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  8. A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

    OpenAIRE

    Koskenvuo, Juha W.; Mirsky, Rachel; Zhang, Yan; Angeli, Franca S.; Jahn, Sarah; Alastalo, Tero-Pekka; Schiller, Nelson B.; Boyle, Andrew J; Chatterjee, Kanu; De Marco, Teresa; Yeghiazarians, Yerem

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigate...

  9. [Management of uncomplicated arterial hypertension in pregnancy].

    Science.gov (United States)

    Gullotti, D; Gullotti, A; Schillaci, L; Lo Genco, A; Figlioli, F; Pira, M; Rotolo, G

    2006-02-01

    In the management of uncomplicated arterial hypertension in pregnancy, blood pressure (BP) values of pregnant women should be treated in order to reduce risks of both maternal and fetal complications. To reduce these risks, it is necessary to monitor BP, some hematochemical parameters and albuminuria, to try to prevent more serious clinical complications. Moreover, repeated measurements of BP, as well as frequent ambulatory blood pressure monitoring (ABPM) over 24 h are necessary. In the treatment of hypertension in pregnancy, if there are no high risks, it is possible to try a non pharmacological antihypertensive therapy consisting of a suitable diet, reduction of weight, abolition of some lifestyles (smoking, excessive alcohol consumption and heavy physical exercises). If these measures are not sufficient or the risk is high, a pharmacological therapy with neither toxic nor teratogenic drugs for the fetus will be administered in order to normalize BP without reducing perfusion of the uterus/placenta. Only in case of severe hypertension, a more aggressive pharmacological treatment should be carried out and, if necessary, hospitalization. The drugs suggested in these cases are those which have already been recognised as presenting low side effects. Antihypertensive drugs used in pregnancy can be classified as: suitable (methyldopa, clonidine, long acting calcioantagonists); cautiously used (alpha-blockers, beta-betablockers); contraindicated (ACE-inhibitors, sartans, short acting calcioantagonists). Hyper-tensive crises should be treated with an injection therapy (clonidine, labetalol), with hospital admission if necessary, or if preeclampsia or eclampsia may occur. PMID:16565702

  10. Endothelin receptor antagonism: role in the treatment of pulmonary arterial hypertension related to scleroderma.

    Science.gov (United States)

    Kabunga, Peter; Coghlan, Gerry

    2008-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease, which is associated with a 1-year survival of about 50% without specific treatment. Pulmonary vascular remodelling, thrombosis and vasoconstriction are thought to be directly involved in increasing pulmonary vascular resistance (PVR), which, left untreated, ultimately leads to right ventricular failure and death. A total of 10-12% of patients with systemic sclerosis (SSc) develop PAH, which is a leading cause of mortality in these patients. Targeted treatment regimens involving oral therapies, in particular endothelin receptor antagonists (ERAs), such as bosentan, sitaxsentan (sitaxentan) and ambrisentan, are now being used and this approach has improved symptoms as well as survival. 1-Year survival has improved to about 80%, while 3-year survival in advanced SSc-PAH has improved from 44% to 65% since the introduction of ERAs. Subanalysis of BREATHE-1, a pilot study and the STRIDE-2X randomized controlled trials has reported improvements in time to clinical worsening, 6-minute walk distance (6mwd) and right heart haemodynamics in SSc-PAH patients given bosentan and sitaxsentan, respectively, compared with placebo. The ARIES studies have also demonstrated a delay in the time to clinical worsening and improvement in 6mwd in connective tissue associated-PAH patients given ambrisentan compared with placebo. Unfortunately, these drugs are expensive and also have the potential for adverse interactions with other PAH and supportive therapies. Mandatory monthly liver function tests are required for safe administration of bosentan, ambrisentan and sitaxsentan, while dose adjustment of warfarin and careful monitoring are required when sitaxsentan is initiated. Earlier diagnosis and treatment of PAH may further improve outcomes with current ERAs. WHO functional class (FC) has traditionally been used to determine which patients with PAH will start therapy. The EARLY study has reported significant reductions in PVR

  11. Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge.

    Science.gov (United States)

    Roldan, Tamara; Landzberg, Michael J; Deicicchi, David J; Atay, Julie K; Waxman, Aaron B

    2016-02-01

    Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk. PMID:26527532

  12. 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.

  13. 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

  14. Drugs and toxins-associated pulmonary arterial hypertension: lessons learned and challenges ahead.

    Science.gov (United States)

    de Jesus Perez, V; Kudelko, K; Snook, S; Zamanian, R T

    2011-01-01

    Since the identification of the link between pulmonary arterial hypertension (PAH) and exposure to certain drugs and toxins nearly fifty years ago, the expanding landscape of available pharmaceuticals and illicit drugs is further fueling this association. While some causative agents in drugs and toxins associated PAH (D&T-APAH) have been identified, little is known about the exact biology and clinical implications of the disease. In this review, we discuss the historical evidence that links PAH with exposure to anorexinogens, cocaine, and methamphetamines and concentrate on what is known about potential pathogenesis, clinical manifestations, and current management. We conclude that future research should focus on studies looking at clinical outcome and susceptibility factors. PMID:21176010

  15. Drug Insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.

    Science.gov (United States)

    Humbert, Marc; Simonneau, Gérald

    2005-12-01

    Rapid advances in the understanding of endothelin as a naturally occurring peptide with developmental and regulatory roles in normal physiology, along with a number of deleterious effects under pathologic conditions (including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation) have led to the development of endothelin-receptor antagonists (ERAs). Bosentan, an antagonist with dual specificity for the endothelin-receptor subtypes A and B, has been shown to be efficacious and well tolerated in placebo-controlled clinical trials and is now approved in many countries, including the US, Canada, and Europe, for treatment of pulmonary arterial hypertension (PAH), including PAH associated with rheumatic diseases. ERAs with specificity for the endothelin-receptor subtype A, including sitaxsentan and ambrisentan, are currently undergoing investigation. This article reviews PAH associated with systemic rheumatic diseases and describes the role of ERAs in this setting. PMID:16932638

  16. Autoimmune hepatitis in a patient with pulmonary arterial hypertension treated with endothelin receptor antagonists.

    Science.gov (United States)

    Naito, Akira; Terada, Jiro; Tanabe, Nobuhiro; Sugiura, Toshihiko; Sakao, Seiichiro; Kanda, Tatsuo; Yokosuka, Osamu; Tatsumi, Koichiro

    2014-01-01

    A 48-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension (PAH) and administered PAH-specific therapies, including bosentan. Four years after the initiation of treatment with bosentan, liver dysfunction appeared, and ambrisentan was substituted for bosentan. One-and-a half years later, a second episode of liver dysfunction occurred. The pathological findings of a liver biopsy specimen were not definitive, although drug-induced hepatotoxicity caused by ambrisentan was considered. However, the patient's liver dysfunction did not improve even after the discontinuation of ambrisentan. Finally, we diagnosed her with autoimmune hepatitis (AIH). Providing careful observation with a suspicion of AIH is important when treating PAH patients with autoantibodies. PMID:24694495

  17. Intratracheal Administration of Prostacyclin Analogue-incorporated Nanoparticles Ameliorates the Development of Monocrotaline and Sugen-Hypoxia-induced Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Kondo, Megumi; Miura, Daiji; Matoba, Tetsuya; Egashira, Kensuke; Ito, Hiroshi

    2016-04-01

    Nanoparticles (NPs) have been used as novel drug delivery systems. Drug-incorporated NPs for local delivery might optimize the efficacy and minimize the side effects of drugs. Intravenous prostacyclin improves long-term survival in patients with pulmonary arterial hypertension (PAH), but it causes serious side effects such as catheter-related infections. We investigated the efficacy and safety of intratracheal administration of a prostacyclin analogue, beraprost (BPS), incorporated NPs in Sugen-hypoxia-normoxia and monocrotaline rat models of PAH and in human PAH pulmonary arterial smooth muscle cells (PASMCs). After a single administration, BPS NPs significantly decreased right ventricular pressure, right ventricular hypertrophy, and pulmonary artery muscularization in the 2 rat models. BPS NPs significantly improved the survival rate in the monocrotaline rat model. No infiltration of inflammatory cells, hemorrhage, or fibrosis was found in the liver, kidney, spleen, and heart after the administration of BPS NPs. No liver or kidney dysfunction was found in the blood examinations. BPS and BPS NPs significantly inhibited the proliferation of human PAH PASMCs after 24 hours of treatment. BPS NPs significantly continued to inhibit the proliferation of human PAH PASMCs at 24 hours after the removal of BPS NPs. BPS NPs significantly induced apoptosis in PAH PASMCs compared to that in non-PAH PASMCs. Intratracheal administration of BPS NPs ameliorates pulmonary hypertension in PAH rat models by a sustained antiproliferative effect and a proapoptotic effect on PAH PASMCs. PMID:26745002

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

    Science.gov (United States)

    Sasagawa, Shota; Nishimura, Yuhei; Sawada, Hirofumi; Zhang, Erquan; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Mitani, Yoshihide; Maruyama, Kazuo; Tanaka, Toshio

    2016-01-01

    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 two genes was significantly increased in the five datasets, whereas expression of SMAD family member six 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 examined Ccdc

  19. Looking to the future: a new decade of pulmonary arterial hypertension therapy

    Directory of Open Access Journals (Sweden)

    V.V. McLaughlin

    2011-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a severe and debilitating disease characterised by vascular proliferation and remodelling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance, increased afterload on the right ventricle and, ultimately, right heart failure. Although there is no “cure” for PAH, the availability of targeted therapies over the past decade has led to major advances in the management of PAH, reflected in improvements in survival in the modern treatment era. However, despite this, disease progression is inevitable in the majority of patients with PAH and overall the long-term prognosis, although improved, remains poor. There is a clear and urgent need for new therapeutic options, either through the development of improved drugs that act on targets established by existing PAH-specific therapies, or of agents targeting novel pathogenic pathways not addressed by currently available therapies. A number of such new agents that have shown promise in experimental models and preliminary human studies are discussed in this article.

  20. 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...

  1. Understanding the impact of pulmonary arterial hypertension on patients' and carers' lives

    Directory of Open Access Journals (Sweden)

    Loïc Guillevin

    2013-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare, debilitating and rapidly progressive disease. Although there have been important medical advances in PAH management, the search for a cure continues. Despite an increased understanding of the disease, data on the wider effect of PAH on patients and carers, beyond the clinical symptoms, are still limited. In order to explore this, a large-scale international survey investigated four key areas affected by PAH (physical and practical, emotional, social, and information needs and provides new insight into patients’ and carers’ experiences of living with the disease. The results from the survey highlight not only the limited ability of patients to carry out everyday tasks, but also the financial impact and social isolation experienced by both patients and carers. The study confirmed that a decline in a patient’s World Health Organization functional class, which indicates an increase in clinical severity of the disease, is associated with greater limitations. Results from the survey demonstrate the need for multidisciplinary PAH management and a comprehensive standard of care to assess and improve all aspects of well-being for both patients and carers. In addition, they underline the need for updated PAH guidelines that address these needs.

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

    Science.gov (United States)

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

    2016-08-01

    Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p Tregs (p Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH. PMID:26319442

  3. 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. PMID:27419193

  4. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    Science.gov (United States)

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

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

    Directory of Open Access Journals (Sweden)

    Farha Samar

    2013-01-01

    Full Text Available Abstract 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 CO of PAH patients did not change over time, 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.

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

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    Sakkas Lazaros

    2009-05-01

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

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

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    M. Rizzo

    2011-09-01

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

  8. Plasma 12- and 15-hydroxyeicosanoids are predictors of survival in pulmonary arterial hypertension

    Science.gov (United States)

    Al-Naamani, Nadine; Sagliani, Kristen D.; Dolnikowski, Gregory G.; Warburton, Rod R.; Toksoz, Deniz; Kayyali, Usamah; Hill, Nicholas S.; Fanburg, Barry L.; Roberts, Kari E.

    2016-01-01

    Abstract This study aimed to characterize alterations in select eicosanoids in experimental and human pulmonary arterial hypertension (PAH) and to assess their potential utility as predictors of outcome. Using liquid chromatography–mass spectrometry, we performed targeted lipidomic analyses of the lungs and right ventricles (RVs) of chronically hypoxic rats and plasma of consecutive PAH patients and healthy controls. In rat lungs, chronic hypoxia was associated with significantly decreased lung prostacyclin (PGI2)/thromboxane B2 (TXB2) ratio and elevated lung 8-hydroxyeicosanoid (HETE) acid concentrations. RV eicosanoids did not exhibit any changes with chronic hypoxia. PAH treatment–naïve patients had significantly increased plasma concentrations of TXB2 and 5-, 8-, 12-, and 15-HETE. The PGI2/TXB2 ratio was lower in PAH patients than in controls, especially in the treatment-naïve cohort (median: 2.1, 0.3, and 1.3 in controls, treatment-naïve, and treated patients, respectively, P = 0.001). Survival was significantly worse in PAH patients with 12-HETEhigh (≥57 pg/mL) and 15-HETEhigh (≥256 pg/mL) in unadjusted and adjusted analyses (hazard ratio [HR]: 2.8 [95% confidence interval (CI): 1.1–7.3], P = 0.04 and HR: 4.3 [95% CI: 1.6–11.8], P = 0.004, respectively; adjustment was performed with the REVEAL [Registry to Evaluate Early and Long-Term PAH Disease Management] risk score). We demonstrate significant alterations in eicosanoid pathways in experimental and human PAH. We found that 12- and 15-HETE were independent predictors of survival in human PAH, even after adjusting for the REVEAL score, suggesting their potential role as novel biomarkers.

  9. Identification of multiple ACVRL1 mutations in patients with pulmonary arterial hypertension by targeted exome capture.

    Science.gov (United States)

    Piao, Chunmei; Zhu, Yan; Zhang, Chen; Xi, Xin; Liu, Xuxia; Zheng, Shuai; Li, Xiaoyan; Guo, Jun; Jia, Lixin; Nakanishi, Toshio; Cai, Tao; Gu, Hong; Du, Jie

    2016-09-01

    Pulmonary artery hypertension (PAH) is characterized as sustained elevation of pressure in the pulmonary vascular system that is attributable to a variety of causes. More than a dozen genes have previously been proposed as being associated with PAH. To examine potential mutations of these genes in patients with PAH, we developed a targeted exome kit containing 22 PAH-associated genes for genetic screens of 80 unrelated patients with PAH. As a result, we identified 16 different mutations in the BMPR2 gene and four different mutations in ACVRL1, the gene for activin receptor-like kinase-1 (ACVRL1). However, no deleterious mutations were found in the remaining 20 genes. In the present study, we provided detailed characterization of the ACVRL1 mutations in four pedigrees, including two novel missense mutations (c.676G>A, p.V226M; c.955G>C, p.G319R) and two recurrent mutations (c.1231C>T, p.R411W; c.1450C>T, p.R484W). Furthermore, we showed that markedly reduced Smad1/5 phosphorylation levels and reduced activities of luciferase reporters in each of the four ACVRL1 mutant-transfected NIH-3T3 cells. Therefore, our findings demonstrated that missense mutations of ACVRL1 identified in the present study significantly affected the bone morphogenetic protein 9 (BMP-9) pathway, implicating PAH pathogenesis. Detailed genotype-phenotype correlation analysis revealed initial symptoms of hereditary haemorrhagic telangiectasia (HHT) in some of the patients, suggesting the importance of sequencing molecular markers for early identification and intervention of individuals at risk for PAH and potential HHT. We developed a customized exome sequencing system to identify mutations in these PAH-associated genes, and found two novel missense mutations and two recurrent mutations in the ACVRL1 gene in four unrelated Chinese families; we also determined hypomorphic alleles using functional studies. PMID:27316748

  10. AMLODIPINE ADVANTAGES IN ARTERIAL HYPERTENSION THERAPY

    Directory of Open Access Journals (Sweden)

    V. M. Tsareva

    2016-01-01

    Full Text Available Aim. To study effects of calcium channel blocker, amlodipine on indices of ambulatory blood pressure monitoring (ABPM, heart rate variability, corrected QT-interval and its dispersion, structural and functional heart indices, microcirculation in patients with arterial hypertension (HT.Material and methods. 48 patients with HT of 1-2 stages were involved in the study. After 2 week wash-out period amlodipine (5-10 mg/day therapy was started. ABPM, 24 hour electrocardiogram monitoring, echocardiography, laser Doppler flowmetry was performed initially and in 24 weeks of therapy.Results. Amlodipine therapy increased microcirculation efficacy, reduced repolarization nonhomogeneity, contributed to myocardial electrophysiological stability. Besides it improved structural and functional heart indices, decreased systolic and diastolic blood pressure (BP, reduced indices of BP load during a day.Conclusion. Amlodipine is effective antihypertensive medicine, having prominent cardio- and vasoprotective effects and good tolerability.

  11. Answers about 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 ...

  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. PMID:26082002

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

    Directory of Open Access Journals (Sweden)

    Cha Gon Lee

    2010-02-01

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

  14. 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

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

    International Nuclear Information System (INIS)

    Increased stiffness of the pulmonary vascular bed is known to increase mortality in patients with pulmonary arterial hypertension (PAH); and pulmonary artery (PA) stiffness is also thought to be associated with exercise capacity. The purpose of the present study was to investigate whether cardiac magnetic resonance imaging (CMRI)-derived PA distensibility index correlates with PA stiffness estimated on right heart catheterization (RHC) and predicts functional capacity (FC) in patients with PAH. Thirty-five consecutive PAH patients (23% male, mean age, 44±13 years; 69% idiopathic) underwent CMRI, RHC, and 6-min walk test (6MWT). PA distensibility indices were derived from cross-sectional area change (%) in the transverse view, perpendicular to the axis of the main PA, on CMRI [(maximum area-minimum area)/minimum area during cardiac cycle]. Among the PA stiffness indices, pulmonary vascular resistance (PVR) and PA capacitance were calculated using hemodynamic dataset from RHC. CMRI-derived PA distensibility was inversely correlated with PVR (R2=0.34, P2=0.35, P2=0.61, P<0.001). Furthermore, PA distensibility <20% predicted poor FC (<400 m in 6MWT) with a sensitivity of 82% and a specificity of 94%. Non-invasive CMRI-derived PA distensibility index correlates with PA stiffness and can predict FC in patients with PAH. (author)

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

    Science.gov (United States)

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

    2009-12-01

    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, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged. PMID:21852894

  17. Asymptomatic Pulmonary Hypertension in Systemic Lupus Erythematosus

    OpenAIRE

    Kamel, Shereen R.; Omar, Gihan M.; Darwish, Ayman F.; Asklany, Hany T.; Abdou S. Ellabban

    2011-01-01

    Introduction: Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of systemic lupus erythematosus (SLE). Because the diagnosis of PAH often is made years after symptom onset, early diagnostic strategies are essential. Doppler echocardiography currently is considered the noninvasive screening test of choice for evaluating pulmonary hypertension. Aim: Screening for asymptomatic pulmonary hypertension in systemic lupus erythematosus patients using Doppler echocardiogr...

  18. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?

    Directory of Open Access Journals (Sweden)

    Andrei Seferian

    2013-09-01

    Full Text Available Pulmonary arterial hypertension (PAH is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the administration inconveniences, represent established therapies for severe cases of PAH. Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug. Sildenafil and tadalafil, two phosphodiesterase type-5 inhibitors, have shown improved exercise capacity by increasing the nitric oxide level. Riociguat, acting on the same nitric oxide pathway, as a guanylatecyclase activator, has shown promising results in clinical trials and will be available soon. Long-awaited results for tyrosin-kinase inhibitor, imatinib, as an antiproliferative therapy in PAH have been disappointing, due to severe adverse events. In conclusion, although it remains a disease with severe prognosis, the past 20 years have represented a huge progress in terms of treatments for PAH with interesting opportunities for the future.

  19. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?

    Science.gov (United States)

    Seferian, Andrei; Simonneau, Gérald

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the administration inconveniences, represent established therapies for severe cases of PAH. Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug. Sildenafil and tadalafil, two phosphodiesterase type-5 inhibitors, have shown improved exercise capacity by increasing the nitric oxide level. Riociguat, acting on the same nitric oxide pathway, as a guanylatecyclase activator, has shown promising results in clinical trials and will be available soon. Long-awaited results for tyrosin-kinase inhibitor, imatinib, as an antiproliferative therapy in PAH have been disappointing, due to severe adverse events. In conclusion, although it remains a disease with severe prognosis, the past 20 years have represented a huge progress in terms of treatments for PAH with interesting opportunities for the future. PMID:23997048

  20. 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.

  1. New perspectives in long-term outcomes in clinical trials of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Ioana R. Preston

    2013-12-01

    Full Text Available The past two decades have seen significant improvements in the management of patients with pulmonary arterial hypertension (PAH. Although outcome has improved, long-term prognosis remains unsatisfactory. The development of new treatment options is clearly important. Equally important is testing new agents in trials designed to provide robust evidence for sustained clinical benefits enabling clinicians to determine the optimal treatment strategy for individual patients. End-points such as the change in 6-min walk distance (6MWD have been pivotal in the registration trials of currently available PAH-specific therapies. However, as current clinical trials enrol patients with milder disease, many already on background therapy, there is growing evidence that change from baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short-term trials allowed for the rapid approval of PAH therapies in the past, there is increasing recognition that clinical trials for new agents must provide evidence of long-term benefits. Clinical trials need to evolve to provide the long-term, clinically relevant data required to appropriately assess new therapies. Event-driven long-term morbidity and mortality trials are currently underway, and will provide robust data on the frequency and timing of events, and are likely to reflect the future of clinical trial design in PAH.

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

    Science.gov (United States)

    Buckley, Mitchell S; Berry, Andrew J; Kazem, Nadine H; Patel, Shardool A; Librodo, Paul A

    2014-01-01

    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. PMID:25018685

  3. Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension.

    Science.gov (United States)

    Steiner, M Kathryn; Preston, Ioana R

    2008-01-01

    Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodynamics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH. PMID:19183742

  4. Safety and tolerability of bosentan in the management of pulmonary arterial hypertension.

    Science.gov (United States)

    Roberts, Kari E; Preston, Ioana R

    2009-01-01

    Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies. PMID:19920927

  5. Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus-infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor

    OpenAIRE

    Pierangelo Chinello; Stefania Cicalini; Simona Pichini; Roberta Pacifici; Massimo Tempestilli; Cicini, Maria P.; Leopoldo P. Pucillo; Nicola Petrosillo

    2015-01-01

    Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH) in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI). We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral the...

  6. Prevalence of breast arterial calcification in hypertensive patients

    Energy Technology Data Exchange (ETDEWEB)

    Cetin, M. E-mail: muzuncetin@yahoo.comakdeniz9999@ttent.net.tr; Cetin, R.; Tamer, N

    2004-01-01

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

  7. Prevalence of breast arterial calcification in hypertensive patients

    International Nuclear Information System (INIS)

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

  8. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    Science.gov (United States)

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension. PMID:26522797

  9. Selexipag for the Treatment of Pulmonary Arterial Hypertension

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. Initial experience with Tadalafil in Pediatric Pulmonary Arterial Hypertension

    OpenAIRE

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

    2012-01-01

    Our objective was to investigate the safety, tolerability, and effects of tadalafil in children with pulmonary arterial hypertension after transition from sildenafil or receiving tadalafil as initial therapy. Thirty three pediatric patients with pulmonary arterial hypertension were retrospectively evaluated. Twenty nine of 33 patients were switched from sildenafil to tadalafil. The main reason for changing from sildenafil was once daily dosing. The average dose of sildenafil and tadalafil wer...

  11. Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Mediated Redox Signaling and Vascular Remodeling by 16α-Hydroxyestrone in Human Pulmonary Artery Cells: Implications in Pulmonary Arterial Hypertension.

    Science.gov (United States)

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

    2016-09-01

    Estrogen and oxidative stress have been implicated in pulmonary arterial hypertension (PAH). Mechanisms linking these systems are elusive. We hypothesized that estrogen metabolite, 16α-hydroxyestrone (16αOHE1), stimulates nicotinamide adenine dinucleotide phosphate oxidase (Nox)-induced reactive oxygen species (ROS) generation and proliferative responses in human pulmonary artery smooth muscle cells (hPASMCs) and that in PAH aberrant growth signaling promotes vascular remodeling. The pathophysiological significance of estrogen-Nox-dependent processes was studied in female Nox1(-/-) and Nox4(-/-) mice with PAH. PASMCs from control subjects (control hPASMCs) and PAH patients (PAH-hPASMCs) were exposed to estrogen and 16αOHE1 in the presence/absence of inhibitors of Nox, cytochrome P450 1B1, and estrogen receptors. Estrogen, through estrogen receptor-α, increased Nox-derived ROS and redox-sensitive growth in hPASMCs, with greater effects in PAH-hPASMCs versus control hPASMCs. Estrogen effects were inhibited by cytochrome P450 1B1 blockade. 16αOHE1 stimulated transient ROS production in hPASMCs, with sustained responses in PAH-hPASMCs. Basal expression of Nox1/Nox4 was potentiated in PAH-hPASMCs. In hPASMCs, 16αOHE1 increased Nox1 expression, stimulated irreversible oxidation of protein tyrosine phosphatases, decreased nuclear factor erythroid-related factor 2 activity and expression of nuclear factor erythroid-related factor 2-regulated antioxidant genes, and promoted proliferation. This was further amplified in PAH-hPASMCs. Nox1(-/-) but not Nox4(-/-) mice were protected against PAH and vascular remodeling. Our findings demonstrate that in PAH-hPASMCs, 16αOHE1 stimulates redox-sensitive cell growth primarily through Nox1. Supporting this, in vivo studies exhibited protection against pulmonary hypertension and remodeling in Nox1(-/-) mice. This study provides new insights through Nox1/ROS and nuclear factor erythroid-related factor 2 whereby 16αOHE1 influences

  12. Heart rate slopes during 6‐min walk test in pulmonary arterial hypertension, other lung diseases, and healthy controls

    OpenAIRE

    Tonelli, Adriano R.; Wang, Xiao‐Feng; Alkukhun, Laith; Zhang, Qi; Dweik, Raed A.; Minai, Omar A.

    2014-01-01

    Abstract Six‐minute walk test (6MWT) continues to be a useful tool to determine the functional capacity in patients with vascular and other lung diseases; nevertheless, it has a limited ability to predict prognosis in this context. We tested whether the heart rate (HR) acceleration and decay slopes during the 6‐m walk test are different in patients with pulmonary arterial hypertension (PAH), other lung diseases, and healthy controls. In addition, we assessed whether the HR slopes are associat...

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

    OpenAIRE

    Bossini-Castillo, L.; Simeón, Carmen P.; Beretta, L; Broen, Jasper C.; Vonk, Madelon C; Callejas-Rubio, J. L.; Carreira, P; Rodríguez-Rodríguez, Luis; García-Portales, Rosa; González-Gay, M. A.; Castellví, I.; Camps, M T; Tolosa, Carlos; Vicente-Rabaneda, Esther; Egurbide, M V

    2012-01-01

    Introduction: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods: The 2,343 SSc cases...

  14. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Schistosomiasis and pulmonary arterial hypertension.

    Science.gov (United States)

    Butrous, Ghazwan

    2014-07-01

    Schistosomiasis is caused by infection with the parasite Schistosoma, which is a flat-worm or fluke. The dominant species are Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium. Schistosomiasis is the third most common parasitic disease in the world after malaria and amoebiasis. It is endemic in more than 70 countries affecting about 200 million people worldwide, of whom 80% are in sub-Saharan Africa. There are pockets of infection in north-eastern Brazil, near the Yangtze River in China, and some pockets in south East Asia. In the East Mediterranean regions, the Schistosoma have been reported in Iraq and Egypt as well as in Sudan. The latter has the highest infection rate nowadays, particularly in the Al Jazeera area, due to the poor Schistosoma control program. In the Arabian peninsula, schistosomiasis has been reported in southwest part of Saudi Arabia, mainly in the Asir province and Jizan province, which lay in the southwest corner of Saudi Arabia and directly north of the border with Yemen. The efforts to control schistosomiasis have been very successful in Saudi Arabia due to the irrigation system control. However, the infection is prone in Yemen, where the schistosomiasis control is much less strict. Thus as a result, the problem still exists due to transmigration of the populations from both countries. As a cause of pulmonary arterial hypertension (PAH), schistosomiasis is still under diagnosed and undertreated. This article with give a highlight about the pathophysiology of the disease and both diagnostic and therapeutic strategies. PMID:25076995

  15. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Schistosomiasis and pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Ghazwan Butrous

    2014-01-01

    Full Text Available Schistosomiasis is caused by infection with the parasite Schistosoma, which is a flat-worm or fluke. The dominant species are Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium. Schistosomiasis is the third most common parasitic disease in the world after malaria and amoebiasis. It is endemic in more than 70 countries affecting about 200 million people worldwide, of whom 80% are in sub-Saharan Africa. There are pockets of infection in north-eastern Brazil, near the Yangtze River in China, and some pockets in south East Asia. In the East Mediterranean regions, the Schistosoma have been reported in Iraq and Egypt as well as in Sudan. The latter has the highest infection rate nowadays, particularly in the Al Jazeera area, due to the poor Schistosoma control program. In the Arabian peninsula, schistosomiasis has been reported in southwest part of Saudi Arabia, mainly in the Asir province and Jizan province, which lay in the southwest corner of Saudi Arabia and directly north of the border with Yemen. The efforts to control schistosomiasis have been very successful in Saudi Arabia due to the irrigation system control. However, the infection is prone in Yemen, where the schistosomiasis control is much less strict. Thus as a result, the problem still exists due to transmigration of the populations from both countries. As a cause of pulmonary arterial hypertension (PAH, schistosomiasis is still under diagnosed and undertreated. This article with give a highlight about the pathophysiology of the disease and both diagnostic and therapeutic strategies.

  16. Early autonomic changes in patients with newly diagnosed arterial hypertension

    Czech Academy of Sciences Publication Activity Database

    Fráňa, P.; Plachý, M.; Jurák, Pavel; Halámek, Josef; Řiháček, I.; Pinková, L.; Souček, M.; Bartošíková, L.; Fráňová, J.

    2010-01-01

    Roč. 28, e-Supplement A (2010), e450. ISSN 0263-6352. [European Meeting on Hypertension /20./. 18.06.2010-21.06.2010, Oslo] Institutional research plan: CEZ:AV0Z20650511 Keywords : arterial hypertension * blood pressure Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  17. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

    Directory of Open Access Journals (Sweden)

    Mehdi Peighambari

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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. [Effect of sanatorium treatment on endothelial function in children with primary arterial hypertension].

    Science.gov (United States)

    Ianina, T Iu

    2014-01-01

    To study the effect of sanatorium treatment (ST) using sodium chloride baths and metabolic drug mildronat on the dynamics of the ambulatory blood pressure monitoring (ABPM), markers of endothelial function in children with primary arterial hypertension (PAH). ABPM and held defined level of asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and nitric oxide (NO) in the serum of 114 children with PAH aged 12-17. The positive dynamics of ABPM in all groups, but significantly (P metabolic therapy, but significantly (P metabolic therapy. Analysis of ET-1 and ADMA at ST in conjunction with therapy and metabolic rate of sodium chloride baths there was a significant (P metabolic therapy helps to reduce average daily blood pressure, normalization of functional activity of the endothelium as a normalization of the synthesis of NO (P < 0.,001), a significant decrease of ET-1 (P < 0.01) and ADMA (P < 0.01). PMID:24908958

  20. Urinoma and arterial hypertension complicating neonatal renal candidiasis

    International Nuclear Information System (INIS)

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

  1. 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.

  2. An inadequate pulmonary vascular capacity and susceptibility to pulmonary arterial hypertension in broilers.

    Science.gov (United States)

    Wideman, R F; Chapman, M E; Hamal, K R; Bowen, O T; Lorenzoni, A G; Erf, G F; Anthony, N B

    2007-05-01

    Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary vascular capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary vascular capacity have been demonstrated experimentally and include elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully engorged vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by

  3. Inaccuracy of doppler echocardiographic estimates of pulmonary artery pressures in adult atrial septal defect patients with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Zhang Caojin; Huang Tao; Huang Xinsheng; Huang Yigao; Chen Jimei; Chen Jiyan; Wu Shulin

    2014-01-01

    Background While echocardiography has been a pivotal screening test in pulmonary arterial hypertension (PAH),the presence of structural cardiac defects may affect the ability to reliably predict pulmonary artery pressures (PAPs).This study sought to evaluate the accuracy of Doppler echocardiography (DE) for estimating PAPs in adult atrial septal defect (ASD) patients with PAH.Methods A prospective study was carried out to compare the echocardiographic assessment of PAP with the same pressures obtained by right heart catheterization (RHC) in adult ASD patients with PAH who underwent simultaneous DE and RHC.Bland-Altman analyses were performed to evaluate the agreement between DE and RHC measurements of PAPs.Results Two hundred and fifty-seven patients were included in the study.A significant overestimation of the systolic pulmonary arterial pressure (sPAP) and mean pulmonary artery pressure (mPAP) was reported by echocardiography compared with those by catheterization ((81.8±26.9) mmHg vs.(72.9±26.9) mmHg,P <0.01; (51.9±16.4) mmHg vs.(41.4±17.2) mmHg,P <0.01,respectively).Twenty-one percent (55/257) of the patients had PAH when estimated by echocardiography whereas showed normal results in the subsequent catheterization test.Using Bland-Altman analytic methods,the bias for the echocardiographic assessment of the sPAP was 9.1 mmHg with 95% limits of agreement ranging from-24.4 to 42.6 mmHg.For mPAP measurement,the bias was 10.5 mmHg with 95% limits of agreement ranging from-12.4 to 33.4 mmHg.On multiple linear regression analysis,age,gender,body surface area,ASDs' diameter,PVR,diastolic blood pressure,and echocardiographic assessment of right atrial pressure (RAP) explained 68.8% of the total variability in the model (r2=0.688,P <0.01).Conclusion Inaccuracy was frequently reported in Doppler echocardiographic assessment of the PAP in adult ASD patients with PAH and was often associated with age,gender,body surface area,ASDs' diameter

  4. Serum Caveolin-1 as a Novel Biomarker in Idiopathic Pulmonary Artery Hypertension

    Directory of Open Access Journals (Sweden)

    Kuo-Yang Wang

    2015-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare disease but with significant morbidity and high mortality. There is no specific way to diagnose PAH. Thus, an easy used with good sensitivity and specificity biomarker of PAH is highly desirable to aid in the screening, diagnosis, and follow-up. Caveolin-1 (Cav1 is the structural protein of caveolae and is highly expressed in type I pneumocytes. Lungs tissues from idiopathic PAH (IPAH patients showed decreased expression of Cav1 in vascular endothelial cells. Therefore, we developed a direct sandwich immunoassay for the determination of Cav1 in IAPH patient’s serum. The result disclosed serum Cav1 level was significantly lower in IPAH than control groups. Using serum Cav1, 17.17 pg/mL as a cutoff value, the sensitivity was 0.59 and the specificity was 1.0. There were two major findings in our results. First, serum Cav1 might be a novel biomarker in the diagnosis of IPAH with fare sensitivity and good specificity. Second, Cav1 might be used to make differential diagnosis between COPD-PH and IPAH group.

  5. 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.

  6. 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

    BACKGROUND AND AIMS: Arterial hypertension is a common disorder. Hyperkinetic circulation and reduced effective volaemia are central elements in the haemodynamic dysfunction in cirrhosis. The aim of the present study was to investigate whether cirrhotic patients with arterial hypertension are...... normokinetic and normovolaemic or whether they reveal the same circulatory dysfunction as their normotensive counterparts. MATERIAL AND METHODS: Thirty three patients with arterial hypertension were identified among 648 patients with cirrhosis: 14 in Child class A, 12 in class B, and seven in class C. Controls...... 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...

  7. 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.

  8. Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Christopher J Valerio

    2009-01-01

    Full Text Available Three different classes of specific therapy exist for pulmonary arterial hypertension. Ambrisentan belongs to the endothelin receptor antagonist (ERA class of drugs, which inhibit the action of Endothelin-1; a potent vasoconstrictor and mitogen. Unlike bosentan and sitaxentan, it has a propanoic-acid based structure and like sitaxentan it has selective affinity for type A Endothelin receptors. Two large randomized controlled trials (ARIES-1 and ARIES-2 have demonstrated clinical benefit with ambrisentan in pulmonary arterial hypertension by repeated measurement of 6-minute walk distance. The most common adverse effect associated with ambrisentan use is peripheral edema, the incidence of liver enzyme elevation seen is lower than for other ERAs. Ambrisentan is safe in combination with warfarin and sildenafil. It offers further flexibility in the treatment of PAH as monotherapy and in combination. Although encouraging, trial data do not exhibit improved efficacy compared with other ERAs or sildenafil and there are no direct comparison studies. Long-term outcome data, including subgroup analysis are awaited to see if there are particular benefits of this therapy in PAH.

  9. Endothelin receptor antagonists for pulmonary arterial hypertension: rationale and place in therapy.

    Science.gov (United States)

    Price, Laura C; Howard, Luke S G E

    2008-01-01

    The last decade has seen significant advances in the understanding and treatment of pulmonary arterial hypertension (PAH). Three main pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in its pathogenesis and these have all led to the development of therapies in current use. While the nitric oxide and prostacyclin pathways require augmentation, the endothelin system is overactive in PAH, with increased endothelin synthesis and receptor expression and, therefore, requires blockade. There are two known endothelin receptors. The type A receptor, expressed in pulmonary artery media, mediates vasoconstriction and remodeling, whereas the function of the type B receptor is more complex. Like the type A receptor, the type B receptor mediates vasoconstriction and remodeling effects when expressed on smooth muscle cells and (myo)fibroblasts, yet functions to clear endothelin from the circulation and induce release of endogenous nitric oxide and prostacyclin, when activated in the pulmonary artery endothelium. Consequently, it is not clear from in vitro data whether the optimal strategy is to block only the type A receptor or both receptors. Phase III clinical studies show clear short-term physiologic benefit with both dual and selective endothelin blockade in PAH. Longer-term experience with bosentan, a dual receptor antagonist, has shown improved outcomes compared with historic control data and comparable survival to intravenous prostacyclin therapy. The newer selective blockers, sitaxsentan and ambrisentan, appear to have similar short-term efficacy, but long-term data are as yet either lacking or unpublished. They may be less hepatotoxic than bosentan, although long-term follow-up of patients receiving bosentan has shown this is not a significant problem. On the basis of available evidence, the endothelin receptor antagonists have become first-line therapy for patients with PAH, except in the most severely affected who still require

  10. 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

  11. 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. PMID:25993253

  12. Arterial stiffness, hypertension, and rational use of nebivolol

    Directory of Open Access Journals (Sweden)

    Enrico Agabiti-Rosei

    2009-05-01

    Full Text Available Enrico Agabiti-Rosei, Enzo Porteri, Damiano RizzoniClinica Medica, Department of Medical and Surgical Sciences, University of Brescia, ItalyAbstract: Arterial stiffness plays a key role in the pathophysiology of the cardiovascular system. Some indices of arterial stiffness (pulse wave velocity, augmentation index, characteristics of central blood pressure waveform may be presently calculated and evaluated in the clinical setting. Age and blood pressure are the two major clinical determinants of increased arterial stiffness, while molecular determinants of arterial stiffness are related to fibrotic components of the extracellular matrix, mainly elastin, collagen and fibronectin. Increased arterial stiffness has been consistently observed in conditions such as hypertension, dyslipidemia and diabetes. Arterial stiffness evaluated by means of carotid-femoral pulse wave velocity yielded prognostic significance beyond and above traditional risk factors. A more favorable effect of calcium channel blockers, diuretics and ACE inhibitors compared with β-blockers on indices of arterial stiffness was observed in several studies. It is conceivable that newer β-blockers with additional vasodilating properties, such as nebivolol, which has favorable effects on carbohydrate and lipid metabolism, as well as on endothelial function and on oxidative stress, may have favorable effects on arterial stiffness, compared with atenolol. In fact, in recent studies, nebivolol was demonstrated to improve artery stiffness to a greater extent than older β-blockers. Because endothelial dysfunction and increased arterial stiffness play an important role in the early atherosclerotic processes and are associated with poor outcomes and increased mortality, independently of blood pressure, the ability of nebivolol to enhance release of endothelium-derived nitric oxide, and consequently improve endothelial function and arterial stiffness, may have significant clinical

  13. 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.

  14. Norepinephrine release in arteries of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

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

  15. Management of pulmonary arterial hypertension associated with congenital heart disease.

    Science.gov (United States)

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

    2007-01-01

    Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data. PMID:18333354

  16. Secondary Pulmonary Arterial Hypertension Treated with Endothelin Receptor Blockade

    OpenAIRE

    Sharma, Sat; Kashour, Tarek; Philipp, Roger

    2005-01-01

    Secondary pulmonary arterial hypertension (SPAH) is an adverse outcome of a variety of systemic disorders. These include collagen vascular diseases, chronic thromboembolism, human immunodeficiency virus, portopulmonary hypertension, and other diseases. Progression of SPAH may persist despite stabilization of the causative disease, thereby contributing to the poor quality of life and unfavorable survival in these patients. Treatment of the underlying cause and oxygen supplementation may allevi...

  17. Modulation of endothelin receptors in the failing right ventricle of the heart and vasculature of the lung in human pulmonary arterial hypertension

    Science.gov (United States)

    Kuc, Rhoda E.; Carlebur, Myrna; Maguire, Janet J.; Yang, Peiran; Long, Lu; Toshner, Mark; Morrell, Nicholas W.; Davenport, Anthony P.

    2014-01-01

    Aims In pulmonary arterial hypertension (PAH), increases in endothelin-1 (ET-1) contribute to elevated pulmonary vascular resistance which ultimately causes death by right ventricular (RV) heart failure. ET antagonists are effective in treating PAH but lack efficacy in treating left ventricular (LV) heart failure, where ETA receptors are significantly increased. The aim was to quantify the density of ETA and ETB receptors in cardiopulmonary tissue from PAH patients and the monocrotaline (MCT) rat, which recapitulates some of the pathophysiological features, including increased RV pressure. Main methods Radioligand binding assays were used to quantify affinity, density and ratio of ET receptors. Key findings In RV from human PAH hearts, there was a significant increase in the ratio of ETA to ETB receptors compared with normal hearts. In the RV of the MCT rat, the ratio also changed but was reversed. In both human and rat, there was no change in LV. In human PAH lungs, ETA receptors were significantly increased in the medial layer of small pulmonary arteries with no change detectable in MCT rat vessels. Significance Current treatments for PAH focus mainly on pulmonary vasodilatation. The increase in ETA receptors in arteries provides a mechanism for the beneficial vasodilator actions of ET antagonists. The increase in the ratio of ETA in RV also implicates changes to ET signalling although it is unclear if ET antagonism is beneficial but the results emphasise the unexploited potential for therapies that target the RV, to improve survival in patients with PAH. PMID:24582810

  18. Essential Arterial Hypertension – Psycho-social Features

    Directory of Open Access Journals (Sweden)

    Adina Karner-HUTULEAC

    2012-12-01

    Full Text Available Essential Arterial Hypertension (EAHT is one of the most spread cardiovascular diseases. EAHT is considered to be a mostly psychosomatic disease, which can affect the psycho-social functioning (depression, anxiety as well as the neuro-cognitive one (attention, memory and executive function disorders. These could lead to the negative influence of the patient and important family members’ level of quality of life. The psycho-social factors (type A behaviour pattern, negative close relationships, social preasure etc. can also influence adherence to treatment and the control of arterial hypertension.

  19. The unique heart sound signature of children with pulmonary artery hypertension.

    Science.gov (United States)

    Elgendi, Mohamed; Bobhate, Prashant; Jain, Shreepal; Guo, Long; Kumar, Shine; Rutledge, Jennifer; Coe, Yashu; Zemp, Roger; Schuurmans, Dale; Adatia, Ian

    2015-12-01

    We hypothesized that vibrations created by the pulmonary circulation would create sound like the vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) might have a unique sound signature. We recorded heart sounds at the cardiac apex and the second left intercostal space (2LICS), using a digital stethoscope, from 27 subjects (12 males) with a median age of 7 years (range: 3 months-19 years) undergoing simultaneous cardiac catheterization. Thirteen subjects had mean pulmonary artery pressure (mPAp) < 25 mmHg (range: 8-24 mmHg). Fourteen subjects had mPAp ≥ 25 mmHg (range: 25-97 mmHg). We extracted the relative power of the frequency band, the entropy, and the energy of the sinusoid formants from the heart sounds. We applied linear discriminant analysis with leave-one-out cross validation to differentiate children with and without PAH. The significance of the results was determined with a t test and a rank-sum test. The entropy of the first sinusoid formant contained within an optimized window length of 2 seconds of the heart sounds recorded at the 2LICS was significantly lower in subjects with mPAp ≥ 25 mmHg relative to subjects with mPAp < 25 mmHg, with a sensitivity of 93% and specificity of 92%. The reduced entropy of the first sinusoid formant of the heart sounds in children with PAH suggests the existence of an organized pattern. The analysis of this pattern revealed a unique sound signature, which could be applied to a noninvasive method to diagnose PAH. PMID:26697170

  20. Exercise testing in the clinical management of patients affected by pulmonary arterial hypertension.

    Science.gov (United States)

    Paolillo, Stefania; Farina, Stefania; Bussotti, Maurizio; Iorio, Annamaria; PerroneFilardi, Pasquale; Piepolil, Massimo F; Agostoni, Piergiuseppe

    2012-10-01

    Patients affected by pulmonary arterial hypertension (PAH) show a reduced exercise tolerance with early occurrence of dyspnoea and fatigue. The origin of functional capacity limitation is multifactorial and several mechanisms have been proposed, including right heart failure, which leads to a limited increase in cardiac output during exercise, and hyperventilation with a reduced perfusion of properly ventilated alveoli. In addition, abnormalities in arterial blood gases are observed, with the occurrence of hypoxemia and hypocapnia, related to an abnormal ventilation/perfusion match, gas diffusion abnormalities, low mixed venous oxygen saturation and to the development of intra- and extra-pulmonary right-to-left shunts. At present, the 6-minute walking test is the most used method to assess exercise tolerance in PAH; it is also useful to monitor the response to therapy and provides prognostic information. However, the assessment of functional capacity by cardiopulmonary exercise test (CPET) seems to be more complete, because CPET allows for discrimination between the metabolic, cardiovascular and pulmonary components of exercise limitation. Moreover, CPET estimates the severity of disease and assesses patients' prognosis and response to therapy. In PAH, a typical CPET-response is observed, characterized by a severe reduction in peak VO2, work rate, O2 pulse and anaerobic threshold and by a marked increase in VE/VCO2 slope and in the dead space to tidal volume ratio. However, the use of CPET should be limited to experienced centres. This review will focus on resting lung function and exercise tolerance tests, showing that CPET can provide the physiological explanation of functional limitation in PAH. PMID:23126000

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Baseline Characteristics and Risk Factors of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus Patients.

    Science.gov (United States)

    Huang, Can; Li, Mengtao; Liu, Yongtai; Wang, Qian; Guo, Xiaoxiao; Zhao, Jiuliang; Lai, Jinzhi; Tian, Zhuang; Zhao, Yan; Zeng, Xiaofeng

    2016-03-01

    Peking Union Medical College Hospital (PUMCH) has started a single-center right heart catheterization (RHC)-based pulmonary arterial hypertension (PAH) study in systemic lupus erythematosus (SLE) since 2006. The baseline characteristics of these patients were described and the risk factor for PAH in lupus was identified.The demographic, clinical, laboratory, and treatment characteristics of SLE patients with PAH when they were registered were collected as the baseline data. A case-control study was conducted by taking the admitted SLE-non-PAH patients adjusted for age and gender in a 4:1 ratio during the same period as the controls. The associated variables were examined by binary multivariate logistic regression analysis to identify possible risk factors. A total of 111 RHC-confirmed SLE-PAH patients were enrolled, with the onset age of 34.6 ± 8.6 years old and the average SLE duration of 5 years. RHC revealed mPAP as 46.4 ± 11.4 mm Hg, CI as 2.7 ± 0.8 L/min × m, and PVR as 10.5 ± 4.8 WU. 46% of patients were WHO Fc I-II. All patients were treated with immunosuppressive agents and 65% patients had PAH-targeted therapy. The case-control study had confirmed 2 independent risk factors previously published: pericardial effusion (OR = 21.290, P RNP antibody (OR = 12.399, P antibody (OR = 4.836, P = 0.004), SLEDAI≤9 (OR = 26.426, P  357 μmol/L (OR = 9.666, P RNP antibody are risk factors for SLE-associated PAH. Long SLE disease duration, the presence of interstitial lung disease, without acute skin rash, positive anti-SSA antibody, low SLEDAI and ESR, and high uric acid levels are also associated with PAH in SLE patients. PMID:26962774

  3. 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.

  4. Successful outcome of pregnancy in RHD with severe MS, severe pulmonary artery hypertension, moderate MR/TR/AR and mild AR

    Directory of Open Access Journals (Sweden)

    Anjali Rani

    2014-06-01

    Full Text Available Rheumatic heart disease with severe Pulmonary Arterial Hypertension (PAH in pregnancy is a grave situation, present with high maternal morbidity and mortality. In this case report, we describe our successful management of such a case which was even more difficult in combination with sever mitral stenosis, severe pulmonary artery hypertension and mild to moderate MR/TR. This patient got her diagnosis late in pregnancy, beyond the time at which a therapeutic termination could not have been performed. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 796-798

  5. 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.)

  6. Hypertension

    Science.gov (United States)

    ... or adrenal-gland disorders. Conditions that can cause secondary hypertension may include: Cushing syndrome Primary aldosteronism Pheochromocytoma Hyperthyroidism Hyperparathyroidism Hypothyroidism Narrowing of the arteries that carry ...

  7. 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.

  8. Lymph node enlargement in pulmonary arterial hypertension due to chronic thromboembolism

    International Nuclear Information System (INIS)

    The aim of this study was to determine the prevalence and location of enlarged mediastinal and hilar lymph nodes in patients with pulmonary arterial hypertension (PAH) due to chronic pulmonary thromboembolism (CPTE) and to identify possible causes. Thoracic CT images of 85 patients(43 men and 42 women, aged 18-80 years) with PAH in whom CPTE was confirmed at surgery (n = 75) or angiography and angioscopy (n = 10) were evaluated by two thoracic radiologists to determine the presence, size and location of lymph nodes more than 1 cm in the short axis. The presence of pleural and pericardial effusions and parenchymal abnormalities were also noted. Enlarged lymph nodes were identified in 38 patients (44.7%), including 11 with possible causes of lymphadenopathy other than CPTE. In the 27 patients with CPTE alone, 67 enlarged lymph nodes were detected (average 2.5 per patient). Nine patients had three or more enlarged lymph nodes. The most common sites of lymph node enlargement were American Thoracic Society locations 7 (n = 13), 6 (n = 10), 11L (n = 9), 10R (n = 7) and 4R (n = 7). Pleural and pericardial effusions were more common in patients with CPTE who also had lymphadenopathy than in the group with no lymphadenopathy (P < 0.05). Lymph node enlargement is common in patients with PAH caused by CPTE. The frequent association of lymphadenopathy with pleural and pericardial effusions suggest a possible pathophysiological mechanism of increased lymphatic flow caused by right heart failure.

  9. Comparative safety and tolerability of endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Aversa, Meghan; Porter, Sandra; Granton, John

    2015-05-01

    Pulmonary arterial hypertension (PAH) is a condition that leads to progressive right heart failure and death unless recognized and treated early. Endothelin, a potent endogenous vasoconstrictor, has been identified as an important mediator of PAH. Endothelin receptor antagonists (ERAs) have been associated with an improvement in exercise capacity and time to clinical worsening in patients with Group 1 PAH, and three different ERAs are currently approved for use in this population: bosentan, ambrisentan, and macitentan. While all three ERAs are generally well-tolerated, they each have important adverse effects that need to be recognized and monitored. In particular, they may cause anemia, peripheral edema, and mild cardiac, respiratory, neurologic, and gastrointestinal adverse effects to varying degrees. Although bosentan increases a patient's risk of developing liver transaminitis, ambrisentan and macitentan do not appear to confer the same risk of hepatotoxicity at this time. Important drug-drug interactions, particularly involving other drugs metabolized via the cytochrome P450 pathway, are important to recognize when prescribing ERAs. In this review, we provide a brief overview of the current state of knowledge as it relates to the adverse effect profiles, tolerability, and drug-drug interactions of this class of medication as informed by the results of randomized clinical trials, drug surveillance programs, and regulatory agencies. PMID:25792028

  10. Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?

    Science.gov (United States)

    Opitz, Christian F; Ewert, Ralf; Kirch, Wilhelm; Pittrow, David

    2008-08-01

    Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ET(A) and ET(B)), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongoing debate as to whether selective or non-selective ET-receptor antagonism is more beneficial in the treatment of PAH. This paper reviews the current evidence from experimental and clinical studies obtained from a thorough literature search focusing on the three marketed drugs bosentan, sitaxentan, and ambrisentan. A clinically meaningful difference among the three approved ETRAs with respect to their ET-receptor selectivity could not be demonstrated to date. Therefore, in clinical practice, other features are likely to be of greater relevance when considering treatment, such as the potential for serious drug-drug interactions, convenience of dosing schedule, or rates of limiting side effects. These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself. PMID:18562303

  11. Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Venitz, Jürgen; Zack, Julia; Gillies, Hunter; Allard, Martine; Regnault, Jean; Dufton, Christopher

    2012-12-01

    The authors review the basic pharmacology and potential for adverse drug-drug interactions (DDIs) of bosentan and ambrisentan, the 2 endothelin receptor antagonists currently approved for pulmonary arterial hypertension (PAH) treatment. Bosentan, an endothelin (ET) receptor-type ET(A) and ET(B) antagonist, is metabolized to active metabolites by and an inducer of cytochrome P450 (CYP)2C9 and CYP3A. Ambrisentan, a selective ET(A) receptor antagonist, is metabolized primarily by uridine 5'diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S and, to a lesser extent, by CYP3A and CYP2C19. Drug interactions observed with bosentan DDI studies have demonstrated a potential for significant clinical implications during PAH management: bosentan is contraindicated with cyclosporine A and glyburide, and additional monitoring/dose adjustments are required when coadministered with hormonal contraceptives, simvastatin, lopinavir/ritonavir, and rifampicin. As bosentan carries a boxed warning regarding risks of liver injury and showed dose-dependant increases in serum aminotransferase abnormalities, drug interactions that increase bosentan exposure are of particular clinical concern. Ambrisentan DDI studies performed to date have shown only one clinically relevant DDI, an interaction with cyclosporine A that requires ambrisentan dose reduction. As the treatment of PAH moves toward multimodal combination therapy, scrutiny should be placed on ensuring that drug combinations achieve maximal clinical benefit while minimizing side effects. PMID:22205719

  12. Managing the Patient with Pulmonary Hypertension: Specialty Care Centers, Coordinated Care, and Patient Support.

    Science.gov (United States)

    Chakinala, Murali M; Duncan, Maribeth; Wirth, Joel

    2016-08-01

    Pulmonary hypertension remains a challenging condition to diagnose and manage. Decentralized care for pulmonary arterial hypertension (PAH) has led to shortcomings in the diagnosis and management of PAH. The Pulmonary Hypertension Association-sponsored Pulmonary Hypertension Care Center program is designed to recognize specialty centers capable of providing multidisciplinary and comprehensive care of PAH. Ideally, Pulmonary Hypertension Care Centers will comanage PAH patients with community-based practitioners and address the growing needs of this emerging population of long-term PAH patients. PMID:27443143

  13. 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

    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....

  14. Pulmonary arterial hypertension as a manifestation of lupus erythematosus

    International Nuclear Information System (INIS)

    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. (orig.)

  15. Сharacteristics of flexible elastic properties of the carotid arteries in women with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Коval О.A.

    2013-10-01

    Full Text Available The article presents the results of study of the features of the carotid wall structure using ultrasound scanning with differential measurement of intima and media thickness, as well as characteristics of arterial elasticity in women with hypertension without comorbidities. It is shown that in women with hypertension vascular remodeling occurs mainly in the form of thickening of the intima-media due to increase in the media layer and is associated with remodeling of the left heart. Carotid remodeling in women with hypertension is associated with worsening of vascular elasticity - increased vascular stiffness and decreased distension, wherein correlation analysis has shown that mentioned parameters are mostly associated with thickening of the medial layer of the artery wall and increase of internal diameter of the artery, as well as with increase in left ventricular mass. Ultrasound method of estimating elastic characteristics of arterial vessels is informative, relatively inexpensive and safe.

  16. Glycogen synthase kinase 3beta contributes to proliferation of arterial smooth muscle cells in pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Piotr Sklepkiewicz

    Full Text Available RATIONALE: Pulmonary arterial hypertension (PAH is a rare progressive pulmonary vascular disorder associated with vascular remodeling and right heart failure. Vascular remodeling involves numerous signaling cascades governing pulmonary arterial smooth muscle cell (PASMC proliferation, migration and differentiation. Glycogen synthase kinase 3beta (GSK3ß is a serine/threonine kinase and can act as a downstream regulatory switch for numerous signaling pathways. Hence, we hypothesized that GSK3ß plays a crucial role in pulmonary vascular remodeling. METHODS: All experiments were done with lung tissue or isolated PASMCs in a well-established monocrotaline (MCT-induced PAH rat model. The mRNA expression of Wnt ligands (Wnt1, Wnt3a, Wnt5a, upstream Wnt signaling regulator genes (Frizzled Receptors 1, 2 and secreted Frizzled related protein sFRP-1 and canonical Wnt intracellular effectors (GSK3ß, Axin1 were assessed by real-time polymerase chain reaction and protein levels of GSK3ß, phospho-GSK3ß (ser 9 by western blotting and localization by immunohistochemistry. The role of GSK3ß in PASMCs proliferation was assessed by overexpression of wild-type GSK3ß (WT and constitutively active GSK3ß S9A by [(3H]-thymidine incorporation assay. RESULTS: Increased levels of total and phosphorylated GSK3ß (inhibitory phosphorylation were observed in lungs and PASMCs isolated from MCT-induced PAH rats compared to controls. Further, stimulation of MCT-PASMCs with growth factors induced GSK3ß inactivation. Most importantly, treatment with the PDGFR inhibitor, Imatinib, attenuated PDGF-BB and FCS induced GSK3ß phosphorylation. Increased expression of GSK3ß observed in lungs and PASMC isolated from MCT-induced PAH rats was confirmed to be clinically relevant as the same observation was identified in human iPAH lung explants. Overexpression of GSK3ß significantly increased MCT-PASMCs proliferation by regulating ERK phosphorylation. Constitutive activation of

  17. Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension.

    Science.gov (United States)

    Takatsuki, Shinichi; Rosenzweig, Erika B; Zuckerman, Warren; Brady, Daniela; Calderbank, Michelle; Ivy, D Dunbar

    2013-01-01

    Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 ± 18 vs. 45 ± 20 mmHg, n = 13, P = 0.04, add-on; 52 ± 17 vs. 45 ± 19 mmHg, n = 13, P = 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4-44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 ± 452 ng/ml, mean time to peak plasma concentration was 3.2 ± 2.1 hours, and mean area under the

  18. The arterial load in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    , 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...... 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......-years, 18 (9%) of the hypertensive subjects developed ischemic heart disease. Microalbuminuria, defined as a urinary albumin/creatinine ratio above the upper decile (1.07 mg/mmol), was the strongest predictor of ischemic heart disease, with an unadjusted relative risk of 4.2 (95% CI 1.5 to 11.9, P=0...

  20. 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 in...... Nijmegen (mean age = 46.2 years; 76.3% with systolic and diastolic hypertension) and 145 patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial (71.0 years) underwent 24-h BP monitoring at a median interval of 8 and 31 days, respectively. We used the repeatability coefficient, which is...... were approximately 30%. Differences in AASI between paired recordings were correlated with differences in the goodness of fit (r2) of the AASI regression line as well as with differences in the night-to-day BP ratio. However, in sensitivity analyses stratified for type of hypertension, r2, or dipping...

  1. Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.

    Science.gov (United States)

    Peng, Xue; Li, Hong-Xia; Shao, Hong-Jiang; Li, Guang-Wei; Sun, Jian; Xi, Yu-Hui; Li, Hong-Zhu; Wang, Xin-Yan; Wang, Li-Na; Bai, Shu-Zhi; Zhang, Wei-Hua; Zhang, Li; Yang, Guang-Dong; Wu, Ling-Yun; Wang, Rui; Xu, Chang-Qing

    2014-11-01

    Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SMα-actin (SMAα), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMAα and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an

  2. Recent trends in pulmonary arterial hypertension

    OpenAIRE

    Rajagopalan Natarajan

    2011-01-01

    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 ...

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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

  6. Сharacteristics of flexible elastic properties of the carotid arteries in women with arterial hypertension

    OpenAIRE

    Коval О.A.; Zubko I.M.

    2013-01-01

    The article presents the results of study of the features of the carotid wall structure using ultrasound scanning with differential measurement of intima and media thickness, as well as characteristics of arterial elasticity in women with hypertension without comorbidities. It is shown that in women with hypertension vascular remodeling occurs mainly in the form of thickening of the intima-media due to increase in the media layer and is associated with remodeling of the left heart. Carotid re...

  7. 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)

  8. 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

  9. Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation

    OpenAIRE

    Sakao Seiichiro; Tatsumi Koichiro; Voelkel Norbert F

    2009-01-01

    Abstract Severe pulmonary arterial hypertension, whether idiopathic or secondary, is characterized by structural alterations of microscopically small pulmonary arterioles. The vascular lesions in this group of pulmonary hypertensive diseases show actively proliferating endothelial cells without evidence of apoptosis. In this article, we review pathogenetic concepts of severe pulmonary arterial hypertension and explain the term "complex vascular lesion ", commonly named "plexiform lesion", wit...

  10. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    OpenAIRE

    Rothman, A.M.K.; Arnold, N D; Chang, W.; Watson, O.; Swift, A J; Condliffe, R; Elliot, C A; Kiely, D. G.; Suvarna, S K; Gunn, J.; Lawrie, A.

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to de...

  11. mTORC2 coordinates pulmonary artery smooth muscle cell metabolism, proliferation and survival in pulmonary arterial hypertension

    Science.gov (United States)

    Goncharov, Dmitry A.; Kudryashova, Tatiana V.; Ziai, Houman; Ihida-Stansbury, Kaori; DeLisser, Horace; Krymskaya, Vera P.; Tuder, Rubin M.; Kawut, Steven M.; Goncharova, Elena A.

    2014-01-01

    Background Enhanced proliferation, resistance to apoptosis and metabolic shift to glycolysis of pulmonary arterial vascular smooth muscle cells (PAVSMC) are key pathophysiological components of pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH). The role of distinct mTOR complexes mTORC1 (mTOR-raptor) and mTORC2 (mTOR-rictor) in PAVSMC proliferation and survival in PAH and their therapeutic relevance is unknown. Methods and Results Immunohistochemical and immunoblot analyses revealed that mTORC1 and mTORC2 pathways are markedly up-regulated in small remodeled PAs and isolated distal PAVSMC from IPAH subjects that have increased ATP levels, proliferation and survival that depend on glycolytic metabolism. siRNA- and pharmacological-based analysis showed that while both mTORC1 and mTORC2 contributing to proliferation, only mTORC2 is required for ATP generation and survival of IPAH PAVSMC. mTORC2 down-regulated energy sensor AMPK allowing activation of mTORC1-S6 and increased proliferation, and deficiency of pro-apoptotic protein Bim and IPAH PAVSMC survival. Nox4 protein levels were increased in IPAH PAVSMC that was necessary for mTORC2 activation, proliferation and survival. Nox4 levels and mTORC2 signaling were significantly up-regulated in small PAs from hypoxia-exposed rats at days 2-28 of hypoxia. Treatment with the mTOR kinase inhibitor PP242 at days 15-28 suppressed mTORC2, but not Nox4, induced SM-specific apoptosis in small PAs and reversed hypoxia-induced pulmonary vascular remodeling in rats. Conclusions These data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via energy sensor AMPK to increased proliferation and survival of PAVSMC in PAH suggesting a new potential pathway for the therapeutic interventions. PMID:24270265

  12. The relationship between the pathologic changes of lung tissue in experimental pulmonary artery hypertension and pulmonary perfusion imaging

    International Nuclear Information System (INIS)

    Objective: To study the relationship between the pathologic changes of lung tissue in experimental pulmonary artery hypertension and pulmonary perfusion imaging. Methods: Twenty-nine japan big-eared white rabbits were used as the animal models. Among them, 13 rabbits underwent pulmonary perfusion imaging, 5 rabbits underwent cardiac catheterization and 2 rabbits underwent lung tissue biopsy before the experiment. Models of pulmonary artery hypertension (PAH) were established in 27 rabbits in different degrees by means of drug and shortage of oxygen. The rabbits were sacrificed after the pulmonary perfusion imaging and the cardiac catheterization to observe the pathological changes of lung tissue. Results: In cases of normal lung tissues, the alveoli and alveolar capsules were uniform in size and there were no dilatation of the arterioles and venulae; In pulmonary perfusion imaging, the radioactivity distribution count ratio of the dorsal side to the ventral side (as apex to bottom in human) was less than 1; The pressure detected by cardiac catheterization was normal. In cases of mild PAH, the lung tissue showed compensatory pulmonary emphysema and dilatation of the venulae; In pulmonary perfusion imaging, the radioactivity distribution count ratio of the dorsal side to the ventral side was more than or equal to 1, and there was difference compared with the normal control (P0.05). In cases of moderate PAH, endothelial cells of the arteriole proliferated and dropped, and the alveoli expanded and fused. In pulmonary perfusion imaging, the radioactivity distribution count ratio of the dorsal side to the ventral side was more than 1. There was significant difference compared with the normal control (P<0.01). The pressure detected by the cardiac catheterization increased significantly too (P<0.05, vs normal control). In severe PAH, hypertrophy was found in muscular layer of arteriole, and stenosis and distortion were found in endomembrane and mid membrane of the

  13. Control of Arterial Hypertension among Type 2 Diabetics

    OpenAIRE

    Ylber Jani; Amet Kamberi; Dali Lala; Gafur Polisi; Mair Iseni; Arben Mirto; Fatmir Ferati; Agim Zeqiri; Atila Rexhepi; Nikola Orovcanec

    2013-01-01

    Arterial hypertension (AH) frequently coexists with diabetes mellitus, occurring twice as frequently in diabetics as in the nondiabetic subjects. AH in diabetic patients is a well-recognized cardiovascular risk factor, accounting for up to 75% of additional cardiovascular disease risks, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with both disorders are prone to a markedly higher risk for premature microvascular and macrovascular co...

  14. Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future.

    Science.gov (United States)

    Lythgoe, Mark P; Rhodes, Christopher J; Ghataorhe, Pavandeep; Attard, Mark; Wharton, John; Wilkins, Martin R

    2016-08-01

    The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). However, against this backdrop, there have been some notable disappointments in drug development. Here we use these as case studies to emphasize the importance of informed drug target selection, the early evaluation of dose-response relationships in human studies, and the value of the deep phenotyping of patients in clinical studies to better understand inter-individual variation in patient response. The integration of "omics" technologies and advanced clinical imaging offer the potential to reduce the risk, and so cost, of drug development in PAH and bring much needed new medicines to those patients most likely to benefit with greater efficiency. PMID:27133570

  15. Current pathophysiological concepts and management of pulmonary hypertension

    OpenAIRE

    Lourenço, AP; Fontoura, D.; Henriques-Coelho, T; Leite-Moreira, AF

    2012-01-01

    Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim ...

  16. Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

    Science.gov (United States)

    Golob, Mark J; Wang, Zhijie; Prostrollo, Anthony J; Hacker, Timothy A; Chesler, Naomi C

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 ± 2 mmHg; Col1a1(R/R): 47 ± 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients. PMID:27252252

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

    Directory of Open Access Journals (Sweden)

    Donna Coffin

    2008-01-01

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

  18. Arterial hypertension aggravates innate immune responses after experimental stroke

    Directory of Open Access Journals (Sweden)

    Karoline Möller

    2015-11-01

    Full Text Available Arterial hypertension is not only the leading risk factor for stroke, but also attribute to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHR and normotensive Wistar Kyoto rats (WKY were subjected to photothrombotic stroke. One and three days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines, along with the post-stroke inflammatory response was analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains four days after stroke. Although comparable at day one, lesion volumes were significantly larger in SHR at day three. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion molecule 1 (VCAM-1 and P-selectin (CD62P was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may

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

    Science.gov (United States)

    Semen, Khrystyna; Yelisyeyeva, Olha; Jarocka-Karpowicz, Iwona; Kaminskyy, Danylo; Solovey, Lyubomyr; Skrzydlewska, Elzbieta; Yavorskyi, Ostap

    2016-04-01

    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. PMID:26654977

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

    OpenAIRE

    Streit Michael; Speich Rudolf; Fischler Manuel; Ulrich Silvia

    2009-01-01

    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 caes...

  1. 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.

  2. Reconciling paradigms of abnormal pulmonary blood flow and quasi-malignant cellular alterations in pulmonary arterial hypertension.

    Science.gov (United States)

    Happé, C M; Szulcek, R; Voelkel, N F; Bogaard, H J

    2016-08-01

    In pulmonary arterial hypertension (PAH) structural and functional abnormalities of the small lung vessels interact and lead to a progressive increase in pulmonary vascular resistance and right heart failure. A current pathobiological concept characterizes PAH as a 'quasi-malignant' disease focusing on cancer-like alterations in endothelial cells (EC) and the importance of their acquired apoptosis-resistant, hyper-proliferative phenotype in the process of vascular remodeling. While changes in pulmonary blood flow (PBF) have been long-since recognized and linked to the development of PAH, little is known about a possible relationship between an altered PBF and the quasi-malignant cell phenotype in the pulmonary vascular wall. This review summarizes recognized and hypothetical effects of an abnormal PBF on the pulmonary vascular bed and links these to quasi-malignant changes found in the pulmonary endothelium. Here we describe that abnormal PBF does not only trigger a pulmonary vascular cell growth program, but may also maintain the cancer-like phenotype of the endothelium. Consequently, normalization of PBF and EC response to abnormal PBF may represent a treatment strategy in patients with established PAH. PMID:26804008

  3. 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. PMID:26993164

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

    Directory of Open Access Journals (Sweden)

    Tiede Henning

    2011-07-01

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

  5. [Emerging therapies for the treatment of pulmonary arterial hypertension].

    Science.gov (United States)

    Ghofrani, Hossein Ardeschir; Voswinckel, Robert; Reichenberger, Frank; Grimminger, Friedrich; Seeger, Werner

    2005-06-01

    Besides all progress in the therapy of pulmonary arterial hypertension over the past years, there is still no cure for this devastating disease. By introducing effective and nonparenteral medications (e. g., oral endothelin receptor antagonists [ERAs], inhaled prostanoids), quality of life, exercise tolerance and prognosis of patients have substantially improved. However, applicability of these therapies can be hampered by serious side effects and/or the necessity for elaborate application techniques. Whether selective ERAs--due to their specificity for the A-type receptor--have potential benefits over the nonselective ERA bosentan remains to be answered by the analysis of pivotal trials recently carried out with ambrisentan and sitaxsentan. Inhaled treprostinil can potentially have benefits over the already approved inhaled iloprost, related to its higher pulmonary selectivity as well as to the longer biological half-life. However, this has yet to be proven in long-term randomized controlled trials. In comparison to the previously mentioned substances, the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil approached approval closest as new therapy for pulmonary arterial hypertension. Oral sildenafil has proven its efficacy as a selective pulmonary vasodilator in various forms of pulmonary hypertension. The results of the pivotal phase III trial have confirmed the strong efficacy and excellent tolerability of this substance. Combination therapies, despite all progress seen for single agents, can be regarded as the most promising therapeutic approach for the future. However, controlled randomized trials that are currently under consideration have to confirm this notion. PMID:15965806

  6. 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

  7. Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gabbay E

    2011-12-01

    Full Text Available Robin Fowler1–3, Sue Jenkins2,3,5, Andrew Maiorana2,4, Kevin Gain2,3,6,7, Gerry O'Driscoll7–9, Eli Gabbay1–3,7–91Advanced Lung Disease Program, Royal Perth Hospital, 2School of Physiotherapy and Curtin Health Innovation Research Institute, Curtin University, 3Lung Institute of Western Australia (LIWA, Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, 4Advanced Heart Failure and Cardiac Transplant Service, Royal Perth Hospital, 5Physiotherapy Department, Sir Charles Gairdner Hospital, 6Respiratory Medicine Department, Royal Perth Hospital, 7School of Medicine, University of Western Australia, 8School of Medicine, University of Notre Dame, 9Heart and Lung Transplant Foundation of Western Australia, Perth, Western Australia, AustraliaAim: To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH.Method: In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO functional classes II–IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities.Results: The response rate was 70% (n = 53. Overall, 58% of respondents recommended patients undertake daily activities 'as tolerated'. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73% and no more than mild light-headedness (92% during daily activities

  8. ARTERIAL HYPERTENSION IN YOUNG PEOPLE: EFFICACY OF SYMPATHOLYTIC THERAPY

    Directory of Open Access Journals (Sweden)

    N. N. Nikitina

    2015-12-01

    Full Text Available Aim. To evaluate the effect of imidasoline agonist, rilmenidine (Albarel, on 24-hour blood pressure (BP profile and autonomic regulation of cardiovascular system in young patients with arterial hypertension (HT and exogenous constitutional obesity (ECO.Material and methods. The study included 80 men aged 18-32 ( average age 20,5 years, including 34 patients with HT and normal body weight, 36 patients with HT and ECO, 10 healthy men as a control group. All hypertensive patients were treated with rilmenidine 1-2 mg daily during 12 weeks. BP 24-hour profile and heart rate variability (HRV were estimated before and after therapy.Results. Rilmenidine monotherapy resulted in significant reduction in average 24-hour, day-time and night-time BP as well as indices of BP loading in both groups. Indices of HRV proved the initial sympathetic overdrive among hypertensive patients especially among those with ECO. This sympathetic overdrive significantly reduced after 12 weeks of therapy.Conclusion. Rilmenidine effectively controls BP and reduces sympathetic system overdrive in young hypertensive patients with ECO.

  9. Epidemiology and prevention of arterial hypertension in Poland.

    Science.gov (United States)

    Zdrojewski, Tomasz; Wyrzykowski, Bogdan; Szczech, Radosław; Wierucki, Lukasz; Naruszewicz, Marek; Narkiewicz, Krzysztof; Zarzeczna-Baran, Marzena

    2005-12-01

    The authors review the present situation in epidemiology and prevention of arterial hypertension in Poland. In 2002, the NATPOL PLUS survey on representative sample of adults (n=3051, age range 18-93) was conducted. Prevalence of hypertension, diagnosed on basis of three separate visits, was 29%, awareness 67% and efficacy of treatment 12.5%. Thus, in Poland, one-third of 8.6 million hypertensives are unaware of their disease. A comparison with data from other countries should be careful due to the different methods (age range, number of readings and visits) used in the studies. The data, in concert with a decrease in awareness of one's own blood pressure (from 71% in 1994 to 59% in 2002), called for urgent preventive measures. Two large interventions were implemented under the National Programme POLKARD in 2003: the Polish 400 Cities Project aimed to increase detection and knowledge of hypertension and other risk factors among small-town and village communities, and the educational project, A Chance for the Young Heart targeted at children aged 11-14 years and using traditional teaching methods and an interactive Internet website. Also, an educational and marketing programme targeted at public opinion leaders and decision makers (trade unions, local governments, healthcare financing authorities, print media and radio, the Polish Parliament) started in 1999 and is still in process. PMID:16429636

  10. Amlodipine induces a flow and pressure-independent vasoactive effect on the brachial artery in hypertension.

    OpenAIRE

    Megnien, J L; Levenson, J.; Del-Pino, M; Simon, A

    1995-01-01

    1. The objectives of this study were to study the flow-dependent arterial reactivity and pressure-independent arterial compliance of the calcium antagonist amlodipine in hypertensive men. 2. Twenty-one hypertensive patients were randomized to receive 2 months treatment with placebo (n = 10) or 5-10 mg amlodipine (n = 11) once a day. Non-invasive measurement of brachial artery mean blood pressure, diameter and flow (pulsed Doppler) and compliance (arterial mechanography and logarithmic elastic...

  11. 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.

  12. Cardiac Autonomic Drive during Arterial Hypertension and Metabolic Disturbances.

    Science.gov (United States)

    Kseneva, S I; Borodulina, E V; Trifonova, O Yu; Udut, V V

    2016-06-01

    ANS support of the cardiac work was assessed with analysis of heart rate variability in representative samples of patients with arterial hypertension and metabolic disturbances manifested by overweight, classes I-II obesity, compromised glucose tolerance, and type II diabetes. Initially enhanced sympathetic effects on the heart rate demonstrated no further increase during the orthostatic test in contrast to suprasegmentary influences enhanced by this test. The pronouncedness of revealed peculiarities in ANS drive to the heart correlated with metabolic disturbances, and these peculiarities attained maximum in patients with type II diabetes. PMID:27383176

  13. Oscillatory contractions in tail arteries from genetically hypertensive rats.

    Science.gov (United States)

    Lamb, F S; Myers, J H; Hamlin, M N; Webb, R C

    1985-01-01

    This study characterizes a cellular mechanism for oscillatory contractions induced by norepinephrine in vascular smooth muscle from spontaneously hypertensive stroke prone rats (SHRSP). Helically cut strips of tail arteries from SHRSP and normotensive Wistar-Kyoto rats (WKY) were mounted in a muscle bath for measurement of isometric force generation. Norepinephrine-induced responses of arteries from SHRSP were characterized by fluctuations in contractile activity, whereas those in arteries from WKY remained constant with time. The magnitude of the oscillatory contractile activity (frequency X mean amplitude) varied directly with norepinephrine concentration (5.9 X 10(-9) to 1.8 X 10(-7) M). The oscillatory contractile activity varied inversely with the potassium concentration (3-20 mM) of the buffer solution and directly with the calcium concentration (0.1-5.0 mM) of the buffer solution. The oscillatory activity was converted to maintained contraction by barium (10(-4) M), quinidine (3 X 10(-6) M), sparteine (10(-3) M), D-600 (10(-7) M), and nifedipine (10(-8) M). Tetraethylammonium and 3,4-diaminopyridine, inhibitors of voltage-dependent potassium channels, did not alter the oscillatory contractile activity induced by norepinephrine. These observations suggest that oscillatory contractile activity in tail arteries from SHRSP is caused by an abnormal variation in potassium efflux during stimulation with norepinephrine. The altered potassium efflux appears to be related to calcium entry, which is sensitive to inhibition by channel blockers. This altered membrane property may contribute to changes in vascular sensitivity in hypertension. PMID:3997233

  14. 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.

  15. Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways

    Science.gov (United States)

    Lee, Mei-Yueh; Tsai, Kun-Bow; Hsu, Jong-Hau; Shin, Shyi-Jang; Wu, Jiunn-Ren; Yeh, Jwu-Lai

    2016-01-01

    Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined. Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factor (PDGF)-BB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase. Liraglutide may have both preventive and therapeutic effects on MCT-induced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling. PMID:27581840

  16. Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case–control study

    OpenAIRE

    Pezzini, A; Caso, V; Zanferrari, C; Del Zotto, E; Paciaroni, M; Bertolino, C; Grassi, M.(INFN Sezione di Roma, Roma, Italy); Agnelli, G.; Padovani, A

    2006-01-01

    Because of the presumed non‐atherosclerotic pathogenesis, the potential link between spontaneous cervical artery dissection (sCAD) and common risk factors for atherosclerosis has never been investigated systematically. Therefore, this prospective, multicentre, case–control study compared the frequency of tobacco use, hypertension, diabetes mellitus, and hypercholesterolaemia among a group of consecutive patients with sCAD (n  =  153), a group of patients with ischaemic stroke, not related to ...

  17. 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. PMID:27468853

  18. 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

  19. Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).

    Science.gov (United States)

    Maron, Bradley A; Waxman, Aaron B; Opotowsky, Alexander R; Gillies, Hunter; Blair, Christiana; Aghamohammadzadeh, Reza; Loscalzo, Joseph; Leopold, Jane A

    2013-09-01

    In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor-mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan + spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings. PMID:23751938

  20. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study.

    Science.gov (United States)

    Khan, Sadiya S; Cuttica, Michael J; Beussink-Nelson, Lauren; Kozyleva, Anastasia; Sanchez, Cynthia; Mkrdichian, Hamorabi; Selvaraj, Senthil; Dematte, Jane E; Lee, Daniel C; Shah, Sanjiv J

    2015-09-01

    Ranolazine, a late inward sodium current and fatty acid oxidation inhibitor, may improve right ventricular (RV) function in pulmonary arterial hypertension (PAH); however, the safety and efficacy of ranolazine in humans with PAH is unknown. Therefore, we sought to (1) determine whether ranolazine is safe and well tolerated in PAH and (2) explore ranolazine's effect on symptoms, exercise capacity, RV structure and function, and hemodynamic characteristics. We therefore conducted a 3-month, prospective, open-label pilot study involving patients with symptomatic PAH (n = 11) and echocardiographic evidence of RV dysfunction. We evaluated the safety and tolerability of ranolazine and compared symptoms, exercise capacity, exercise bicycle echocardiographic parameters, and invasive hemodynamic parameters between baseline and 3 months of ranolazine therapy using paired t tests. Of the 11 patients enrolled, one discontinued ranolazine therapy due to a drug-drug interaction after 3 days of therapy. All 10 of the remaining patients continued therapy for 3 months, and 8 (80%) of 10 completed all study tests. After 3 months, ranolazine administration was safe and associated with improvement in functional class (P = 0.0013), reduction in RV size (P = 0.015), improved RV function (improvement in RV strain during exercise at 3 months; P = 0.037), and a trend toward improved exercise time and exercise watts on bicycle echocardiography (P = 0.06 and 0.01, respectively). Ranolazine was not associated with improvement in invasive hemodynamic parameters. In conclusion, in a pilot study involving PAH, ranolazine therapy was safe and well tolerated, and it resulted in improvement in symptoms and echocardiographic parameters of RV structure and function but did not alter invasive hemodynamic parameters. ClinicalTrials.gov Identifier: NCT01174173. PMID:26401256

  1. Effect of dual pulmonary vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease: a retrospective analysis

    Science.gov (United States)

    Monfredi, Oliver; Heward, Elliot; Griffiths, Linda; Condliffe, Robin; Mahadevan, Vaikom S

    2016-01-01

    Background Patients with pulmonary arterial hypertension (PAH) are managed according to evidence-based treatment guidelines. Methods and results In this single-centre retrospective analysis, we examined outcomes of patients with PAH caused by congenital heart disease (PAH-CHD) with respect to exercise capacity and survival of adults treated with either bosentan or sildenafil monotherapy or bosentan-sildenafil dual therapy between January 2007 and January 2014. Of the 82 patients analysed, 29 had Down syndrome; 54 (65.8%) received bosentan monotherapy, 16 (19.5%) sildenafil monotherapy and 12 (14.6%) dual therapy. Mean treatment duration was 2.5 years for all patients and 4.1 years for 38 patients treated for ≥2 years. Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD). For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy. Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively. Conclusions For the majority of patients, monotherapy with a PAH-specific medication provided improved and sustained exercise benefits. For the small percentage of patients who required it, add-on therapy appeared to prevent further deterioration in exercise capacity but did not improve 6MWD. PMID:27099763

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

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Hi [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1984-09-15

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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Pfarr Nicole

    2013-01-01

    Full Text Available Abstract Background Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic or heritable pulmonary arterial hypertension (I/HPAH with children affected with congenital heart defects associated PAH (CHD-APAH. Methods Prospectively included were 40 consecutive children with invasively diagnosed I/HPAH or CHD-APAH and 117 relatives. Assessment of family members, pedigree analysis and systematic screening for mutations in TGFß genes were performed. Results Five mutations in the bone morphogenetic protein type II receptor (BMPR2 gene, 2 Activin A receptor type II-like kinase-1 (ACVRL1 mutations and one Endoglin (ENG mutation were found in the 29 I/HPAH children. Two mutations in BMPR2 and one mutation in ACVRL1 and ENG, respectively, are described for the first time. In the 11 children with CHD-APAH one BMPR2 gene mutation and one Endoglin gene mutation were found. Clinical assessment of relatives revealed familial aggregation of the disease in 6 children with PAH (HPAH and one CHD-APAH patient. Patients with mutations had a significantly lower PVR. Conclusion Mutations in different TGFß genes occurred in 8/29 (27.6% I/HPAH patients and in 2/11 (18.2% CHD-APAH patients and may influence the clinical status of the disease. Therefore, genetic analysis in children with PAH, especially in those with I/HPAH, may be of clinical relevance and shows the complexity of the genetic background.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue.

    Science.gov (United States)

    Sobolewski, Anastasia; Rudarakanchana, Nung; Upton, Paul D; Yang, Jun; Crilley, Trina K; Trembath, Richard C; Morrell, Nicholas W

    2008-10-15

    Heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II receptor cause familial pulmonary arterial hypertension (PAH). We previously demonstrated that the substitution of cysteine residues in the ligand-binding domain of this receptor prevents receptor trafficking to the cell membrane. Here we demonstrate the potential for chemical chaperones to rescue cell-surface expression of mutant BMPR-II and restore function. HeLa cells were transiently transfected with BMPR-II wild type or mutant (C118W) receptor constructs. Immunolocalization studies confirmed the retention of the cysteine mutant receptor mainly in the endoplasmic reticulum. Co-immunoprecipitation studies of Myc-tagged BMPR-II confirmed that the cysteine-substituted ligand-binding domain mutation, C118W, is able to associate with BMP type I receptors. Furthermore, following treatment with a panel of chemical chaperones (thapsigargin, glycerol or sodium 4-phenylbutyrate), we demonstrated a marked increase in cell-surface expression of mutant C118W BMPR-II by FACS analysis and confocal microscopy. These agents also enhanced the trafficking of wild-type BMPR-II, though to a lesser extent. Increased cell-surface expression of mutant C118W BMPR-II was associated with enhanced Smad1/5 phosphorylation in response to BMPs. These findings demonstrate the potential for rescue of mutant BMPR-II function from the endoplasmic reticulum. For the C118W mutation in the ligand-binding domain of BMPR-II, cell-surface rescue leads to at least partial restoration of BMP signalling. We conclude that enhancement of cell-surface trafficking of mutant and wild-type BMPR-II may have therapeutic potential in familial PAH. PMID:18647753

  7. Current management approaches to portopulmonary hypertension.

    OpenAIRE

    O'Callaghan, Dermot,; Savale, Laurent; Magnier, Romain; LE PAVEC, JEROME; Herve, Philippe; Jais, Xavier; Seferian, Andrei; Humbert, Marc; Simonneau, Gerald; Sitbon, Olivier

    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...

  8. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Saleh, Soundos; Becker, Corina; Frey, Reiner; Mück, Wolfgang

    2016-03-01

    This analysis aimed to characterize the pharmacokinetics (PK) and PK/pharmacodynamic (PK/PD) relationship of riociguat and its metabolite M1 in patients with chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH). Blood samples were collected in two phase 3 studies-PATENT-1 (Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1; 12 weeks; PAH) and CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1; 16 weeks; CTEPH)-and long-term extensions. Patients were initially randomized to receive placebo or riociguat, and they received riociguat in the extensions. Nonlinear mixed-effects modeling was used to develop a population PK model describing riociguat PK. PK/PD relationships were investigated by comparing derived PK parameters with changes in PD parameters. Covariate analyses included smoking status, bosentan comedication, bilirubin levels, and baseline creatinine clearance. The PK of riociguat/M1 was described by a one-compartment model. Mean population estimates for riociguat absorption rate constant, clearance, and volume of distribution were 2.17/h, 1.81 L/h, and 32.3 L, respectively; for M1 they were 0.258/h, 3.16 L/h, and 124 L. Interindividual variability was moderate for riociguat and moderate to high for M1. There was no evidence of time- or dose-dependent changes in riociguat/M1 PK. Riociguat clearance was higher in smokers (120% increase) and bosentan-treated patients (36% increase) than in nonsmokers and those not receiving bosentan. There was an inverse correlation between bilirubin and riociguat clearance. In PK/PD analyses, 6-minute walk distance was related to hemodynamic parameters, particularly pulmonary vascular resistance. Riociguat PK were described by a one-compartment model. Effects of covariates on riociguat and M1 PK were established, and a PK/PD relationship was demonstrated. (ClinicalTrials.gov identifiers: PATENT-1, NCT00810693

  9. 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 and...... significant increase of systemic arterial vascular tone in patients with essential hypertension during the first half of the night compared to normotensive control subjects....... was significantly higher in 31 patients with essential hypertension compared to 30 normotensive control subjects (30.0+/-0.2 vs 28.8+/-0.2; P=0.001). In patients with essential hypertension, the reflective index significantly increased from 30.0+/-0.2 in the first half (from 2301 to 0230) to 30...

  10. Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment epithelium diastasis in heritable pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Li, Xiao Qiang; Pryds, Anders; Carlsen, Jørn;

    2015-01-01

    PURPOSE: To report atypical central serous chorioretinopathy and choroidal thickening in a patient with heritable pulmonary arterial hypertension. METHODS: A 40-year-old man with heritable pulmonary arterial hypertension presented with blurred vision in his left eye and was followed up for 1 year...... chorioretinopathy and choroidal thickening that responded to treatment of pulmonary arterial hypertension suggest a pathophysiological link between pulmonary arterial hypertension and central serous chorioretinopathy, perhaps mediated by choroidal venous stasis....... choroidal vessels were seen in the patient's symptomatic left eye. After treatment for pulmonary hypertension, the serous detachments disappeared and choroidal thickness gradually decreased over a period of 4 weeks and remained unchanged at 13 months of follow-up. CONCLUSION: Central serous...

  11. A low resting heart rate at diagnosis predicts favourable long-term outcome in pulmonary arterial and chronic thromboembolic pulmonary hypertension. A prospective observational study

    Directory of Open Access Journals (Sweden)

    Hildenbrand Florian F

    2012-09-01

    Full Text Available Abstract Background A low resting heart rate (HR is prognostically favourable in healthy individuals and in patients with left heart disease. In this study we investigated the impact of HR at diagnosis on long-term outcome in patients with differently classified precapillary pulmonary hypertension (pPH. Methods pPH patients diagnosed as pulmonary arterial (PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH were registered and regularly followed at our centre Baseline characteristics and events defined as either death or lung transplantation were noted. The prognostic value of HR was analysed using Kaplan Meier estimates, live tables and Cox regression. Results 206 patients with PAH (148 and inoperable CTEPH (58 were included. The median HR was 82 bpm. pPH with a HR below 82 bpm had a significantly longer overall event-free survival (2409 vs.1332 days, p = .000. This advantage was similarly found if PAH and CTEPH were analysed separately. Although a lower HR was associated with a better hemodynamic and functional class, HR was a strong and independent prognostic marker for transplant free survival even if corrected for age, sex, hemodynamics and functional status. Conclusion We show that resting HR at diagnosis is a strong and independent long-term prognostic marker in PAH and CTEPH. Whether reducing HR by pharmacological agents would improve outcome in pPH has to be assessed by future trials with high attention to safety.

  12. Enhanced vasodilator responses to calcitonin gene-related peptide (CGRP) in subcutaneous arteries in human hypertension

    DEFF Research Database (Denmark)

    Lind, H; Edvinsson, L

    2002-01-01

    Isolated segments (1-2 mm) of small subcutaneous arteries (diameter 0.1-0.9 mm) and veins (0.1-1.0 mm) from patients with hypertension (essential n = 13, renovascular n = 6) and controls (n = 17) were examined. The relaxant responses to the sensory transmitters calcitonin gene-related peptide (CGRP......) and substance P, and the contractile responses to potassium and noradrenaline were studied. Enhanced dilatory responses (E(max)) but no change in sensitivity (pEC50) were demonstrated in the arteries but not in the veins to CGRP in hypertensives (P < 0.01) as compared with normotensives, and in the...... hypertensive subgroups (essential hypertension, P < 0.05; renovascular hypertension, P< 0.05). The relaxant responses to substance P were not altered either in arteries or in veins of hypertensives. Furthermore, there were no differences in the contractile responses to 60 mM potassium or to 10 micro...

  13. Gender, sex hormones and pulmonary hypertension

    OpenAIRE

    Austin, Eric D.; Johansen, Anne Katrine; Alzoubi, Abdallah; Lahm, Tim; West, James; Tofovic, Stevan P.; MacLean, Margaret R.; Oka, Masahiko

    2013-01-01

    Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging ...

  14. 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

  15. Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

    Directory of Open Access Journals (Sweden)

    Rushi V Parikh

    Full Text Available HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.We measured ET-1 and estimated pulmonary artery systolic pressure (PASP with transthoracic echocardiography (TTE in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65 underwent right heart catheterization (RHC to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively in the multivariable analyses.Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH.

  16. Evaluation of the grading and disorder assessment of congenital heart disease with pulmonary arterial hypertension

    International Nuclear Information System (INIS)

    Pulmonary arterial hypertension is one of the most common and serious complications in congenital heart disease. Identification of whether the pulmonary, arterial hypertension is dynamic or resistance remains as the great importance for deciding to transfer for surgery, intervention or conservative therapy and directly concerning with the prognosis and choice of treatment. This review mainly deals with the problems such as grading, staging, pathophysiology and the correlative mechanism with clinical assessment of pulmonary. arterial hypertension in congenital heart disease and furthermore providing comprehensive informations for clinical diagnosis and treatment. (authors)

  17. Pulmonary Vascular Pressure Profiles in Broilers Selected for Susceptibility to Pulmonary Hypertension Syndrome: Age and Gender Comparisons

    OpenAIRE

    Wideman, R. F.; Eanes, M. L.; Hamal, K. R.; Anthony, N. B.

    2010-01-01

    Broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) have an elevated pulmonary arterial pressure (PAP) when compared with PHS-resistant broilers. Two distinctly different syndromes, pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH), both are associated with increases in PAP. Pulmonary arterial hypertension occurs when the right ventricle must elevate the PAP to overcome increased resistance to flow through restrictive pulmonary arteriole...

  18. Severe Hypertension Secondary to Renal Artery Stenosis and Cushing's Syndrome

    International Nuclear Information System (INIS)

    We present an unusual patient who simultaneously had severe renal artery stenosis RAS and Cushings syndrome. The case highlights the difficulty of reaching a specific diagnosis of Cushings syndrome and the possible interaction between Cushings syndrome and some other concurrent illnesses that this patient had. A 37-year old man presented with severe hypertension HTN and uncontrolled diabetes mellitus DM without clear physical signs of Cushings syndrome. He was found to have severe osteoporosis, proximal myopathy, several cutaneous warts, tinea versicolor, and chronic viral hepatitis. Captopril-stimulated renal scan and renal artery angiogram revealed severe RAS. Partial balloon dilatation of RAS led to improvement in HTN. Unexpectedly, urine free cortisol 24 hour was found extremely high. Serum adrenocorticotropic hormone ACTH was also elevated and high dose dexamethasone suppression tests were inconclusive. Several imaging studies failed to localize the source of ACTH. Despite normal MRI of the pituitary gland, bilateral inferior petrosal sinus sampling IPSS localized the source of ACTH secretion to the right side of the pituitary gland and right anterior hemihypophysectomy resulted in cure of Cushings disease, HTN, DM, and tinea versicolor with significant improvement in cutaneous warts, osteoporosis, and chronic hepatitis. In conclusion, RAS and Cushings syndrome may occur together. Significant hypercortisolemia can occur without clear signs of Cushings syndrome. Controlling hypercortisolemia is of paramount importance when treating chronic infections in patients with Cushing's syndrome. (author)

  19. Symptom Prevalence, Symptom Severity, and Health-Related Quality of Life Among Young, Middle, and Older Adults With Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Matura, Lea Ann; McDonough, Annette; Carroll, Diane L

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a chronic, life threatening illness that affects primarily women. The purpose of this study was to describe the prevalence of PAH symptoms and to determine whether there are differences in symptom severity and HRQOL in PAH symptoms among young, middle, and older adults with PAH. A cross sectional design was utilized. For all the age groups, shortness of breath (SOB) on exertion and fatigue were the two most prevalent symptoms. SOB on exertion had the highest symptom severity scores followed by fatigue for all groups. Symptom severity was significantly different among the groups for palpitations, abdominal swelling and nausea. For components of HRQOL, physical functioning worsened with age. All groups had diminished general health, role physical and vitality levels. There are some differences in symptom prevalence, symptom severity and HRQOL among young, middle and older adults. Awareness of these differences is important for healthcare providers to know and assess overtime. Palliative care should be an integral part of caring for patients with PAH. PMID:25294227

  20. Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

    OpenAIRE

    Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M.; Andrew H. Baker; MacLean, Margaret R.

    2012-01-01

    Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmo...

  1. Treatment of hypertension in patients with renal artery stenosis due to fibromuscular dysplasia of the renal arteries

    OpenAIRE

    Chrysant, Steven G; Chrysant, George S.

    2014-01-01

    Renal artery stenosis (RAS) from fibromuscular dysplasia (FMD) is an uncommon cause of hypertension that affects mostly women. FMD is a noninflammatory vascular disease that predominantly affects mainly the renal arteries, but can also affect arteries in other vascular territories. The most common type of FMD is the media fibroplasia with the characteristic “string of beads” appearance (80-90%), whereas the two other types, the “intimal” and “adventitial” FMD are much less common accounting f...

  2. 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.

  3. 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.

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

    International Nuclear Information System (INIS)

    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

  5. Non-invasive stroke volume assessment in patients with pulmonary arterial hypertension: left-sided data mandatory

    Directory of Open Access Journals (Sweden)

    Westerhof Nico

    2008-11-01

    Full Text Available Abstract Background Cardiovascular Magnetic Resonance (CMR is an emerging modality in the diagnosis and follow-up of patients with Pulmonary Arterial Hypertension (PAH. Derivation of stroke volume (SV from the pulmonary flow curves is considered as a standard in this respect. Our aim was to investigate the accuracy of pulmonary artery (PA flow for measuring SV. Methods Thirty-four PAH patients underwent both CMR and right-sided heart catheterisation. CMR-derived SV was measured by PA flow, left (LV and right ventricular (RV volumes, and, in a subset of nine patients also by aortic flow. These SV values were compared to the SV obtained by invasive Fick method. Results For SV by PA flow versus Fick, r = 0.71, mean difference was -4.2 ml with limits of agreement 26.8 and -18.3 ml. For SV by LV volumes versus Fick, r = 0.95, mean difference was -0.8 ml with limits of agreement of 8.7 and -10.4 ml. For SV by RV volumes versus Fick, r = 0.73, mean difference -0.75 ml with limits of agreement 21.8 and -23.3 ml. In the subset of nine patients, SV by aorta flow versus Fick yielded r = 0.95, while in this subset SV by pulmonary flow versus Fick yielded r = 0.76. For all regression analyses, p Conclusion In conclusion, SV from PA flow has limited accuracy in PAH patients. LV volumes and aorta flow are to be preferred for the measurement of SV.

  6. Relationship of sonographic wall components of the brachial artery to hypertension and coronary atherosclerosis

    OpenAIRE

    Frick, Matthias; Alber, Hannes F; Rinner, Alexander; Suessenbacher, Alois; Ulmer, Hanno; Schwarzacher, Severin P; Pachinger, Otmar; Weidinger, Franz

    2005-01-01

    Abstract The aim of this study was to determine whether sonographically assessed intimal (echodense, ED) or medial (echolucent, EL) thickening of the brachial artery is associated with coronary artery disease (CAD) and/or arterial hypertension (HT). In 201 patients the ED and EL wall components, as well as the total wall thickness of the brachial artery, were measured with high-resolution ultrasound (13 MHz). According to the presence or absence of CAD and HT, the patients were div...

  7. In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat

    OpenAIRE

    Morgan, Eric E.; Casabianca, Andrew B; Khouri, Samer J; Kalinoski, Andrea L. Nestor

    2014-01-01

    Background Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive r...

  8. 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.

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

    Science.gov (United States)

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

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

  10. Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

    DEFF Research Database (Denmark)

    Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning;

    2006-01-01

    Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys......; epithelial Na channel-alpha; 11beta-hydroxysteroid dehydrogenase type 2) were increased. These data suggest enhanced volume conservation by the kidney. Our data define ISIAH as an attractive model for the renal components determining salt and water homeostasis in hypertension. The specific condition of a...

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

    International Nuclear Information System (INIS)

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

  12. PHARMACOECONOMIC ANALYSIS OF OUTPATIENT COMBINED THERAPY OF ARTERIAL HYPERTENSION AND HYPERCHOLESTEROLEMIA

    OpenAIRE

    Egorova, E.; Okonenko, L.; Bondarenko, O.

    2011-01-01

    Pharmacoeconomic analysis of outpatient therapy for patients with diagnosis of arterial hypertension (AH) and hypercholesterolemia has been carried out. Result of treatment is estimated by reducing risk of cardiovascular death.

  13. Factors Affecting the Response to Exercise in Patients with Severe Pulmonary Arterial Hypertension

    OpenAIRE

    Flox-Camacho, Ángela; Escribano Subías, Pilar; Jiménez-Lépez Guarch, Carmen; Fernández Vaquero, Almudena; Martín Ríos, María Dolores; Saenz de la Calzada-Campo, Carlos

    2011-01-01

    Introduction: Ergospirometry objectively quantifies exercise capacity. Up until now, the response to exercise evaluated by ergospirometry in patients with pulmonary arterial hypertension has only been described in recently diagnosed.patients. Our aim is to describe the response to exercise in patients with severe pulmonary arterial hypertension under specific treatment and define which parameters determine their exercise capacity. Patients and method: A cross-sectional study was performed on ...

  14. Evaluation of the pharmacological treatment of arterial hypertension associated to heart failure in Camarones town.

    OpenAIRE

    Pedro Miguel Milián Vázquez; Idalmis Pérez Alemán; Carlos Martín Álvarez; Maira Quirós Enríquez.; Lidia Vázquez Montero

    2006-01-01

    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’ Communita...

  15. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    OpenAIRE

    M. V. Leonova

    2015-01-01

    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. 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

  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. Bleeding Esophageal Varices and Portal Hypertension Caused by Arteriovenous Fistula of Splenic Artery

    OpenAIRE

    Moshe Shleapnik; Baruch Shpitz; Annette Siegal; Alex Dinbar

    1990-01-01

    Splenic arteriovenous fistula is a rare but curable cause of portal hypertension. This report describes a patient with such a disorder, presenting with bleeding esophageal varices and ascites. It emphasises the importance of performing selective catheterization of the celiac and superior mesenteric artery in all patients with signs of portal hypertension without evidence of chronic liver disease. Etiopathology and management are discussed.

  19. 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...... potential canonical (TRPC) channels, in the present study we tested the hypothesis that increased vasomotion in hypertension is directly linked to increased TRPC expression. Using a small vessel myograph we observed significantly increased norepinephrine-induced vasomotion in mesenteric arterioles from SHR...... vasomotion in hypertension....

  20. 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.

  1. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. HEMODYNAMIC EFFECTS OF CARVEDILOL IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    L. I. Markova

    2016-01-01

    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.

  5. Pharmacoeconomic evidence of bosentan for pulmonary arterial hypertension.

    Science.gov (United States)

    Strange, Geoff; Keogh, Anne; Dalton, Brad; Gabbay, Eli

    2011-06-01

    In this article, we review randomized controlled trials, open-label trials and pharmacoeconomic models of bosentan for the management of patients with pulmonary arterial hypertension. Bosentan consistently improves WHO functional class and quality of life, slows clinical worsening and is associated with improved survival compared with historical treatment. Although head-to-head trials are scarce, data directly comparing bosentan with sildenafil indicate no clinically significant differences between treatments as measured by the 6-min walk distance alone. Compared with historical care, bosentan treatment, over a 15-30-year period, increases the number of quality-adjusted life years (3.49 years). Economic modeling suggests that the cost-effectiveness of bosentan is similar to that of ambrisentan (US$43,725-57,778 per quality-adjusted life year), not as cost effective as sildenafil (at 20 mg three-times daily) and more cost effective than iloprost. More randomized controlled trials of longer duration are required to confirm the results from these economic models. PMID:21671693

  6. REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

    OpenAIRE

    Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

    2012-01-01

    Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair...

  7. Nitrite Signaling in Pulmonary Hypertension: Mechanisms of Bioactivation, Signaling, and Therapeutics

    OpenAIRE

    Bueno, Marta; Wang, Jun; Mora, Ana L.; Gladwin, Mark T.

    2013-01-01

    Significance: Pulmonary arterial hypertension (PAH) is a disorder characterized by increased pulmonary vascular resistance and mean pulmonary artery pressure leading to impaired function of the right ventricle, reduced cardiac output, and death. An imbalance between vasoconstrictors and vasodilators plays an important role in the pathobiology of PAH. Recent Advances: Nitric oxide (NO) is a potent vasodilator in the lung, whose bioavailability and signaling pathway are impaired in PAH. It is n...

  8. Hypertrophy and hyperplasia of smooth muscle cells of small intramyocardial arteries in spontaneously hypertensive rats.

    Science.gov (United States)

    Amann, K; Gharehbaghi, H; Stephen, S; Mall, G

    1995-01-01

    Hearts of stroke-prone spontaneously hypertensive rats (SHR) were investigated by means of stereology and were compared with those of normotensive. Wistar-Kyoto controls. At the age of 9 months, hypertensive rats showed cardiac hypertrophy, marked myocardial fibrosis, activation of nonvascular interstitium, focal myocytial degeneration, reduction of capillarization, and microarteriopathy of small intramyocardial arteries. Stereologically, a significant increase in the total left ventricular arterial wall volume (+180% versus controls) was found in SHR hearts. By using new stereological techniques, the orientator and the nucleator, we investigated whether this significant increase in total left ventricular arterial wall volume was due to hyperplasia of smooth muscle cells in addition to the process of vascular smooth muscle cell hypertrophy that is common in SHR. Additionally, the nuclear size and ratio of cell volume to nuclear volume were determined using another new stereological technique, the selector. The stereological data indicate a significant increase in mean cell and nuclear volumes as well as in the total number of left ventricular arterial smooth muscle cells of SHR. Additionally, the total length of intramyocardial arteries was also significantly increased in hypertensive rats. The volume and number of arterial smooth muscle cells per arterial length were significantly (P < .001 and P < .05, respectively) higher in SHR than in normotensive controls. Thus, we conclude that hypertrophy and hyperplasia of smooth muscle cells are involved in intramyocardial arterial growth processes in hypertensive heart remodeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843743

  9. 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 the...

  10. Renal artery aneurysm in a hypertensive child treated by percutaneous coil embolization

    International Nuclear Information System (INIS)

    A 16-year-old boy was admitted to our hospital with uncontrolled hypertension. A left renal artery aneurysm was detected on colour Doppler US and CT. Renal arteriography demonstrated the aneurysm and focal renal parenchymal areas of decreased perfusion. The renal artery aneurysm was successfully treated by transcatheter coil embolization. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2005-09-01

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

  12. 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......). Conclusion Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk. J Hypertens 25:1021-1026 Q 2007 Lippincott Williams & Wilkins. Journal of Hypertension 2007, 25:1021-1026...... uncomplicated essential hypertensive patients. Recently, high M: L was demonstrated as a prognostic marker in patients at high cardiovascular risk, including normotensive type 2 diabetic patients. Since diabetes is associated with pressure-independent changes in M: L, the relevance of this finding to essential...

  13. Doppler sonographic evaluation of ophthalmic arterial flow pattern in hypertensive patients

    International Nuclear Information System (INIS)

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

  14. 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.

  15. Idiopathic Pulmonary Arterial Hypertension: An Avian Model for Plexogenic Arteriopathy and Serotonergic Vasoconstriction

    OpenAIRE

    Wideman, Robert F.; Hamal, Krishna R.

    2011-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance attributable to vasoconstriction and vascular remodeling of small pulmonary arteries. Vascular remodeling includes hypertrophy and hyperplasia of smooth muscle (medial hypertrophy) accompanied in up to 80% of the cases by the formation of occlusive plexiform lesions (plexogenic arteriopathy). Patients tend to be unrespo...

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

    Science.gov (United States)

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

    2016-01-01

    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression. PMID:26733189

  17. 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.

  18. [The role of the team of family physician in prevention of changing risk factors important in development of arterial hypertension].

    Science.gov (United States)

    Beganlić, Azijada; Batić-Mujanović, Olivera; Tulumović, Ajsa; Zilzić, Muharem

    2005-01-01

    Arterial hypertension (AH) is one of the commonest noninfective chronic disease according to its important and the role in the morbidity and mortality, which is the reason for patients coming to the family phisician. Detection and treatment of high blood pressure are the major responsibility of physician in the primary care. If the family physician team (physician and nurse) make a good assessment of the risk factors which is important in development of arterial hypertension, the appearance of disease and its complications can be prevented or delayed. The most important for prevention of arterial hypertension is adoption a healthy lifestyle and it is nonseparate part of arterial hypertension treatment. PMID:16268072

  19. Acute Response of Right Ventricular Function to Iloprost Inhalations in Patients with Pulmonary Arterial Hypertension: Preliminary Evaluation 
with Cardiac Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Qingqing LU

    2015-03-01

    Full Text Available Background and objective Pulmonary arterial hypertension (PAH is a progressive disorder characterized by abnormally elevated blood pressure of the pulmonary circulation. Without treatment, PAH progresses rapidly to right ventricular (RV failure and even death. Cardiac magnetic resonance imaging (CMRI has been an accurate and reproducible tool to assessment of RV morphology and function, which are important factors in the prognosis of patients with PAH. The aim of this study is to investigate acute RV response to inhalation of aerosolized iloprost in patients with PAH using CMRI. Method From March 2012 to March 2014, 48 patients with PAH underwent CMRI before and immediately after inhalation of iloprost with a single dose of 20 μg over 15 min-20 min. RV function parameters derived from CMRI images were analyzed before and after iloprost inhalation, including end-diastolic volume (EDV, end-diastolic area (EDA, end-systolic volume (ESV, end-systolic area (ESA, stroke volume (SV, ejection fraction (EF and cardiac output (CO. Percentage of RV area change was also calculated [%RVAC=(EDA-ESA/EDA×100%]. Wilcoxon's Sign Rank Test or Paired Samples t-Test was used to compare the differences of RV function parameters before and after inhalation. Results After iloprost inhalation, all patients showed significant decrease in RV EDV and RV ESV (P=0.007, P<0.001 respectively. Whereas, there were significant increase in RV SV (P=0.014, RV EF (P=0.009 and %RVAC (P=0.006. RV CO had no significant difference before and after inhalation (P=0.851. Conclusions Inhalation of iloprost can immediately improve RV function in patients with PAH, and noninvasive evaluation of the acute response with CMRI is feasibility.

  20. Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

    International Nuclear Information System (INIS)

    Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 ± 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n = 53), and group II - men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter (β), augmentation index (AI) and one-point pulse wave velocity (PWV-β) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness. - Highlights: → Amongst persons with AH exposed to Pb higher ZnPP represent independent risk factor of increased local arterial stiffness. → Higher Pb

  1. MANAGEMENT OF PULMONARY HYPERTENSION AT CHILDREN AND ADOLESCENTS

    OpenAIRE

    Alina-Costina LUCA; Mariana PAGUTE; Constantin IORDACHE

    2016-01-01

    Pulmonary arterial hypertension (PAH) is considered a rare disease in the pediatric population, is idiopathic or associated with congenital heart disease, it is rarely associated with connective tissue disease, it represents an important cause of morbidity and mortality. According to data from the Netherlands, the incidence and prevalence is 0.7 and 4.4 for idiopathic PAH and 2.2 and 15.6 for PAH associated with congenital heart disease, cases per one million children. Selective vasodilator t...

  2. The Relationship between the Breast Arterial Calcification Detected by Mammography and the Hypertensive Retinopathy in Hypertensive Women

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the relationship between the breast arterial calcification (BAC) detected by mammograms and the hypertensive retinopathy (HR) in hypertensive women who underwent ophthalmologic examination. Screening mammography was performed in 99 hypertensive women and these women also underwent an ophthalmologic examination. The presence of arterial calcification and the number of calcified blood vessels in each breast were evaluated. The grade of HR was determined. The presence of BAC and the number of blood vessels involved was compared according to the presence of HR and the grade of HR. Among the 99 patients, HR was detected in 70 patients, and of these 70 patients, 42 patients had grade I HR and 28 had grade II HR. BAC was detected in 54 cases. Forty-six patients with HR (66%) and eight patients without HR (27%) were diagnosed with BAC after they underwent mammographic examination. The prevalence of BAC in the subjects who had HR was statistically higher than that in those subjects who did not have HR (p 0.05). The positive predictive value of the BAC detected on mammography for HR was 0.80 in those subjects who were 60 years old. The detection of BAC by mammography is associated with an increased risk of HR, and particularly for patients after the age of 60. The findings of BAC may be related to hypertensive end-organ damage, and performing mammograms might contribute to predicting the presence of ophthalmologic hypertensive complications in these patients

  3. 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

    )-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP......)/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...... was increased (Ø: 385±13 to 463±14 μm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 × 10(3)±1 × 10(3) μm(2)). The diameter of the HF arteries of normotensive rats increased (Ø: 463±22 μm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471±16 μm). MrA from SOL...

  4. Calcium antagonist verapamil prevented pulmonary arterial hypertension in broilers with ascites by arresting pulmonary vascular remodeling.

    Science.gov (United States)

    Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming

    2007-04-30

    Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers. PMID:17320074

  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. MDCTA diagnosis of cerebral vessel disease among patients with arterial hypertension

    International Nuclear Information System (INIS)

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

  7. Altered endothelin receptor expression and affinity in spontaneously hypertensive rat cerebral and coronary arteries

    DEFF Research Database (Denmark)

    Cao, Lei; Cao, Yong-Xiao; Xu, Cang-Bao;

    2013-01-01

    BACKGROUND: Hypertension is associated with arterial hyperreactivity, and endothelin (ET) receptors are involved in vascular pathogenesis. The present study was performed to examine the hypothesis that ET receptors were altered in cerebral and coronary arteries of spontaneously hypertensive rats...... (SHR). METHODOLOGY/PRINCIPAL FINDINGS: Cerebral and coronary arteries were removed from SHR. Vascular contraction was recorded using a sensitive myograph system. Real-time PCR and Western blotting were used to quantify mRNA and protein expression of receptors and essential MAPK pathway molecules. The...... results demonstrated that both ETA and ETB receptor-mediated contractile responses in SHR cerebral arteries were shifted to the left in a nonparallel manner with increased maximum contraction compared with Wistar-Kyoto (WKY) rats. In SHR coronary arteries, the ETA receptor-mediated contraction curve was...

  8. Cerebral Perfusion Measurements in Elderly with Hypertension Using Arterial Spin Labeling

    DEFF Research Database (Denmark)

    Mutsaerts, H J M M; van Dalen, J W; Heijtel, D F R;

    2015-01-01

    PURPOSE: The current study assesses the feasibility and value of crushed cerebral blood flow (CBFcrushed) and arterial transit time (ATT) estimations for large clinical imaging studies in elderly with hypertension. MATERIAL AND METHODS: Two pseudo-continuous arterial spin labeling (ASL) scans with...... (CBFcrushed) and without flow crushers (CBFnon-crushed) were performed in 186 elderly with hypertension, from which CBF and ATT maps were calculated. Standard flow territory maps were subdivided into proximal, intermediate and distal flow territories, based on the measured ATT. The coefficient of variation...... group analyses in elderly with hypertension. The obtained flow territories provide knowledge on vascular anatomy of elderly with hypertension and can be used in future studies to investigate regional vascular effects....

  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. 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

  11. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep

    OpenAIRE

    Dodson, R. Blair; Morgan, Matthew R.; Galambos, Csaba; Hunter, Kendall S.; Abman, Steven H.

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characteriz...

  12. Modeled PFOA Exposure and Coronary Artery Disease, Hypertension, and High Cholesterol in Community and Worker Cohorts

    OpenAIRE

    Winquist, Andrea; Steenland, Kyle

    2014-01-01

    Background: Several previous studies, mostly cross-sectional, have found associations between perfluorooctanoic acid (PFOA) and high cholesterol levels, but studies of hypertension and heart disease have had inconsistent findings. Objectives: In this study we examined the association between modeled PFOA exposure and incident hypertension, hypercholesterolemia, and coronary artery disease among workers at a Mid-Ohio Valley chemical plant that used PFOA, and residents of the surrounding commun...

  13. Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofilariasis.

    Science.gov (United States)

    Kitagawa, H; Sasaki, Y; Ishihara, K; Hirano, Y

    1990-12-01

    To investigate whether adult heartworms harboring in the pulmonary arteries contribute to pulmonary hypertension, we determined the cardio-pulmonary values immediately before and after removal of heartworms from the pulmonary arteries and before and after insertion of live worms in their place. In 10 heartworm-infected dogs, 8 to 46 worms were removed. The mean pulmonary arterial pressure fell significantly from 24.5 +/- 7.9 mmHg to 16.3 +/- 4.9 mmHg (p less than 0.01) immediately after removal. The right cardiac output decreased in 7 of the 10 cases. The total pulmonary resistance and right ventricular stroke work index also decreased. At 24 hours after removal, live heartworms were put back into the pulmonary arteries of their host dog. The mean pulmonary arterial pressure elevated significantly (p less than 0.01) immediately after insertion. The right cardiac output further decreased in 7 of the 10 dogs, and the total pulmonary resistance and right ventricular stroke work index increased. Separate from this, 12 to 42 heartworms were transplanted into the pulmonary arteries of 5 heartworm-free dogs. Immediately after transplantation, the pulmonary arterial pressure did not show any significant change. However, the stroke volume decreased, and the total pulmonary resistance increased. These facts suggest a contribution of live heartworms to the pulmonary hypertension, although there is a complicated interaction among the presence of heartworms, the pulmonary lesions and the pulmonary hypertension. PMID:2287128

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

    OpenAIRE

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

    2013-01-01

    Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption...

  15. Hemodynamics, function and perfusion of the myocardium in arterial hypertensive with varying left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Seventy eight patients with arterial hypertension were examined by echo-, radiocardiography and scintigraphy of the myocardium, using 99mTc pyrophosphate and 201Tl. A relationship was found between the development of hypertrophy of the left ventricle and the impairment of it perfusion and function. At the same time there was a correlation benween the decrease in cardiac output and the deterioration of myocardial blood supply. It was demonstrated that 99mTc pyrophosphate or 201Tl myocardial scintigraphy yielded the coincident results when relative heart failure was evaluated in patients with arterial hypertension and left ventricular hypertropy

  16. [Innovative instruction for assisting patients with arterial hypertension].

    Science.gov (United States)

    Bontemps, S; Pechère-Bertschi, A

    2015-09-01

    The MOOC In The Heart of Hypertension is an innovative online training for students and health providers. Its aim is to strengthen skills for professionals caring people suffering from hypertension. A MOOC is a free online training aiming unlimited participation. It widely promotes a high quality education. Medical and paramedical training recently seized upon this powerful tool, for initial and continuing training. Indeed, MOOC responds to several pedagogic challenges, particularly through educational strategies focused on the learner's skills: mastery of pedagogy, retrieval practice and peer grading. This MOOC about hypertension aims at responding to the needs of caregivers to enhance their therapeutic support skills. PMID:26540996

  17. 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

    International Nuclear Information System (INIS)

    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

  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

    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.

  19. Hipertensão arterial pulmonar associada à anemia falciforme Sickle cell anemia-associated pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. Relationship Between Carotid Artery Calcification Detected in Dental Panoramic Images and Hypertension and Myocardial Infarction

    OpenAIRE

    Moshfeghi, Mahkameh; Taheri, Jamileh Beigom; Bahemmat, Nika; Evazzadeh, Mohammad Ebrahim; Hadian, Hoora

    2014-01-01

    Background: Carotid artery calcification may be related to cerebrovascular accident, which may result in death or physical and mental disabilities in survivors. Objectives: Our purpose is to study the association of carotid artery calcification (CAC) on dental panoramic radiographs and two risk factors of cerebrovascular accident (CVA) including hypertension and myocardial infarction (MI). Patients and Methods: Panoramic images of 200 patients that were all women above 50 years of age (a popu...

  3. Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension

    OpenAIRE

    Li, Zhuangjie; Huang, Wei; Jiang, Zong Lai; Gregersen, Hans; Fung, Yuan-Cheng

    2004-01-01

    The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thickness...

  4. Portopulmonary hypertension.

    Science.gov (United States)

    Lv, Yong; Han, Guohong; Fan, Daiming

    2016-07-01

    Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non-specific, patients should be actively screened for the presence of PoPH. Two-dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. PMID:27002212

  5. Renovascular hypertension

    Science.gov (United States)

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... blood pressure to rise. Risk factors for atherosclerosis: High blood pressure Smoking Diabetes High cholesterol Heavy alcohol use Cocaine ...

  6. Arterial Hypertension in a Child with Williams-Beuren Syndrome (7q11.23 Chromosomal Deletion

    Directory of Open Access Journals (Sweden)

    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.

  7. Simultaneous microdetermination of bosentan, ambrisentan, sildenafil, and tadalafil in plasma using liquid chromatography/tandem mass spectrometry for pediatric patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Yokoyama, Yoshinari; Tomatsuri, Miho; Hayashi, Hideki; Hirai, Keita; Ono, Yasuo; Yamada, Yuto; Todoroki, Kenichiro; Toyo'oka, Toshimasa; Yamada, Hiroshi; Itoh, Kunihiko

    2014-02-01

    A simultaneous, selective, sensitive, and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of bosentan, ambrisentan, sildenafil, and tadalafil in 50μL of human blood plasma. Diluted plasma samples were extracted using a solid-phase extraction procedure with 2% formic acid and methanol. The four drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2mL/min for 5min. The drugs were detected by a tandem mass spectrometer with electrospray ionization using deuterated compounds as internal standards. Calibration curves were generated over the linear concentration range of 2-1000ng/mL in plasma with a lower limit of quantification of 2ng/mL for all compounds. Finally, this validated method was applied to a clinical pharmacokinetic study in pediatric patients with pulmonary arterial hypertension (PAH) following the oral administration of PAH drugs. These results indicate that this method is suitable for assessing the risk/benefit of combination therapy in the pediatric population and useful for therapeutic drug monitoring for PAH treatment. PMID:24309556

  8. A history of arterial hypertension does not affect mortality in patients hospitalised with congestive heart failure

    DEFF Research Database (Denmark)

    Gustafsson, F; Torp-Pedersen, C; Seibaek, M;

    2006-01-01

    OBJECTIVES: To evaluate the importance of a history of hypertension on long-term mortality in a large cohort of patients hospitalised with congestive heart failure (CHF). DESIGN: Retrospective analysis of 5491 consecutive patients, of whom 24% had a history of hypertension. 60% of the patients ha...... studies, could not be confirmed. CONCLUSION: A history of arterial hypertension did not affect mortality in patients hospitalised with CHF.......OBJECTIVES: To evaluate the importance of a history of hypertension on long-term mortality in a large cohort of patients hospitalised with congestive heart failure (CHF). DESIGN: Retrospective analysis of 5491 consecutive patients, of whom 24% had a history of hypertension. 60% of the patients had...... with a history of hypertension. 72% of the patients died during follow up. A hypertension history did not affect mortality risk (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.92 to 1.07). Correction for differences between the normotensive and hypertensive groups at baseline in a multivariate...

  9. Application of A Microstructural Constitutive Model of the Pulmonary Artery to Patient-Specific Studies: Validation and Effect of Orthotropy

    OpenAIRE

    Zhang, Yanhang; Dunn, Martin L.; Hunter, Kendall S.; Lanning, Craig; Ivy, D. Dunbar; Claussen, Lori; Chen, S. James; Shandas, Robin

    2007-01-01

    We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying...

  10. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    Directory of Open Access Journals (Sweden)

    Aditya Bhat

    2015-01-01

    Full Text Available Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials.

  11. 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

  12. Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

    International Nuclear Information System (INIS)

    A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient

  13. Smooth Muscle Proliferation and Role of the Prostacyclin (IP) Receptor in Idiopathic Pulmonary Arterial Hypertension

    OpenAIRE

    Falcetti, Emilia; Hall, Susan M.; Phillips, Peter G.; Patel, Jigisha; Morrell, Nicholas W.; Haworth, Sheila G; Clapp, Lucie H.

    2010-01-01

    Rationale: Prostacyclin analogs, used to treat idiopathic pulmonary arterial hypertension (IPAH), are assumed to work through prostacyclin (IP) receptors linked to cyclic AMP (cAMP) generation, although the potential to signal through peroxisome proliferator-activated receptor-γ (PPARγ) exists.

  14. Autoregulation of brain circulation in severe arterial hypertension

    DEFF Research Database (Denmark)

    Strandgaard, S; Olesen, Jes; Skinhoj, E;

    1973-01-01

    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 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....

  15. Basic human needs affected for arterial hypertension and Lifestyle

    OpenAIRE

    Gleudson Alves Xavier; Maysa Oliveira Rolim; Vera Maria da Conceição Lopes de Sousa; Maria Euridéa de Castro

    2003-01-01

    Knowing that hypertension is a chronic disease, in which the individual may have his basic needs changed, resulting in having to learn to deal with a new life-style, we considered it appropriate to study this theme. It was designed to identify the affected basic needs and to discover the influence of life-style and of hypertension in alteration of those needs. The study is a descriptive-exploratory, accomplished at the Campus of a State Public University in Fortaleza – Ceará, Brazil. This stu...

  16. 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

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

    International Nuclear Information System (INIS)

    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

  18. Long-term prognosis after acute myocardial infarction in patients with a history of arterial hypertension. TRACE study group

    DEFF Research Database (Denmark)

    Gustafsson, F; Køber, L; Torp-Pedersen, C;

    1998-01-01

    AIMS: The objective of the study was to investigate the influence of a history of arterial hypertension on long-term prognosis after an acute myocardial infarction in a representative population, and secondly to assess the impact on prognosis of left ventricular systolic function in hypertensives...... patients had a history of arterial hypertension. During the time of observation 763 (50.6%) hypertensives and 2253 (43.7%) normotensives died, corresponding to a risk ratio for death in hypertensives of 1.23 (1.13-1.33, P < 0.0001). In a multivariate analysis considering 12 other major risk factors after....... CONCLUSION: A history of arterial hypertension is a moderate risk factor for mortality after an acute myocardial infarction in patients aged 65 years or less. This excess risk is present at all levels of left ventricular systolic function....

  19. Contribution of arterial hypertension to vascular risk in diabetic patients

    OpenAIRE

    Marre, M.; Bouhanick, B.; Hadjadj, S.; Weekers, Laurent

    1999-01-01

    Hypertension is a major cardiovascular risk factor in diabetic subjects. Recent trials have suggested that blood pressure objectives should be < or = 140/80 mmHg. However, there is currently no evidence supporting any particular preferential drug strategy for this treatment objective. Peer reviewed

  20. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension.

    Science.gov (United States)

    Krasińska, Beata; Miazga, Angelika; Cofta, Szczepan; Szczepaniak-Chicheł, Ludwina; Trafas, Tomasz; Krasiński, Zbigniew; Pawlaczyk-Gabriel, Katarzyna; Tykarski, Andrzej

    2016-05-27

    INTRODUCTION    Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH). Apnea episodes cause hypoxia, which triggers the activation of the renin-angiotensin-aldosterone system. This leads to water retention and swelling in the neck region, exacerbating OSA symptoms. It is assumed that the use of eplerenone may reduce the swelling and thus alleviate the severity of OSA. OBJECTIVES    We aimed to prospectively assess the impact of eplerenone on the severity of OSA and arterial stiffness in patients with RAH. PATIENTS AND METHODS    The study included 31 patients with RAH and OSA. The exclusion criteria were as follows: secondary hypertension, myocardial infarction, stroke 6 months prior to the study, congestive heart failure, chronic kidney failure, alcohol or drug addiction, and active cancer. In all patients, the following tests were performed: blood pressure (BP) measurement (traditionally and using ambulatory BP measuring [ABPM]), applanation tonometry, polysomnography, and the apnea-hypopnea index (AHI) calculation. The tests were done before and after 3 months of eplerenone therapy. Patients received 50 mg of oral eplerenone daily, along with other hypertensive drugs. RESULTS    The mean age of participants was 57.76 ±6.16 years. After 3 months of eplerenone therapy, we observed a significant reduction in the AHI, neck circumference, BP, aortic pulse wave, and arterial wall stiffness. There were significant correlations between the AHI and mean BP measured by ABPM and between the AHI and arterial stiffness parameters. CONCLUSIONS    Our results provide evidence for the clinical significance of eplerenone, not only as an antihypertensive medication but also as a drug that may reduce the severity of OSA and arterial stiffness in patients with RAH and OSA. PMID:27230560

  1. Age dependent dynamics of intima-media complex thickness in elderly patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Sadjaya L.A.

    2011-09-01

    Full Text Available Aim: To estimate the dynamics of intima-media complex in elderly patients with arterial hypertension. Materials: 179 elderly patients with arterial hypertension were involved in the study. Mean intima-media wall thickness (IMT of common carotid arteries in plaque-free sites and prevalence of plaques were evaluated by B-mode ultrasound investigation (Philips Envisor HD, USA. Results: IMT changing was of nonlinear character, remained stable up to 74 years. Mean rate of the following IMT augmentation was 0.157 mm per year. Frequency of atherosclerotic plaque revealing was significantly increased since the 7th decade. Significant correlation between IMT and systolic, diastolic, mean blood pressure levels or medication spectrum was not revealed. Conclusion: Received data proved significant influence of aging upon IMT enlargement

  2. 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, and...... evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed...... uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P<0.001) on both univariate and...

  3. Dried Blood Spot Technique for the Monitoring of Ambrisentan, Bosentan, Sildenafil, and Tadalafil in Patients with Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Enderle, Yeliz; Meid, Andreas D; Friedrich, Jörg; Grünig, Ekkehard; Wilkens, Heinrike; Haefeli, Walter E; Burhenne, Jürgen

    2015-12-15

    Endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5I) are long-term therapeutics for the treatment of pulmonary arterial hypertension (PAH). Their interindividual pharmacokinetic variability is remarkably large, and despite the seriousness of the disease, nonadherence is occurring. Therefore, methods to monitor sufficient circulating drug levels are essential. The objectives of this study were to develop and validate dried blood spot (DBS) assays for the quantification of ambrisentan, bosentan, sildenafil, tadalafil, and their main metabolites. We also quantified the influence of different hematocrit levels and assessed the correlation of simultaneously taken capillary whole blood (DBS) and venous plasma samples. The aliquot punches were extracted by liquid/liquid extraction followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) quantification methods. All assays fulfilled the requirements of the FDA and EMA guidelines for assay validation with a lower limit of quantification of 2.5 ng/mL for the ERAs, 5 ng/mL for sildenafil, and 10 ng/mL for tadalafil. All analytes were stable for at least 147 days when stored on DBS filter paper cards at room temperature in the dark. Due to poor distribution into erythrocytes, drug concentrations in DBS were always lower than in plasma, resulting in conversion factors of 1.58 for ambrisentan and sildenafil and 1.52 for bosentan and tadalafil. PMID:26583764

  4. Cerebral White Matter and Retinal Arterial Health in Hypertension and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    P. L. Yau

    2013-01-01

    Full Text Available We examined 33 hypertensive (22 with comorbid type 2 diabetes mellitus (T2DM and 29 normotensive (8 with T2DM middle-aged and elderly adults, comparable in age and education. Relative to normotensive participants, those with hypertension, in addition to a higher prevalence of periventricular white matter (WM lesions, had significantly lower WM microstructural integrity of major fiber tracts as seen with MRI-based diffusion tensor imaging. Among participants with hypertension, those with co-morbid T2DM (n=22 had more widespread WM pathology than those without T2DM (n=11. Furthermore and consistent with previous research, both hypertension and T2DM were related to decreased retinal arterial diameter. Further exploratory analysis demonstrated that the observed retinal arteriolar narrowing among individual with hypertension was associated with widespread subclinical losses in WM microstructural integrity and these associations were present predominantly in the frontal lobe. We found that T2DM adds to the damaging effects of hypertension on cerebral WM, and notably these effects were independent of age and body mass index. Given that the decrease in retinal arteriolar diameter may be a biomarker for parallel pathology in cerebral arterioles, our data suggest that the frontal lobe may be particularly vulnerable to microvascular damage in the presence of hypertension and T2DM.

  5. 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

  6. 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. PMID:26979941

  7. Intratracheal Gene Transfer of Adrenomedullin Using Polyplex Nanomicelles Attenuates Monocrotaline-induced Pulmonary Hypertension in Rats

    OpenAIRE

    Harada-Shiba, Mariko; Takamisawa, Itaru; Miyata, Kanjiro; Ishii, Takehiko; Nishiyama, Nobuhiro; Itaka, Keiji; Kangawa, Kenji; Yoshihara, Fumiki; Asada, Yujiro; Hatakeyama, Kinta; Nagaya, Noriya; Kataoka, Kazunori

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive PAH and right ventricular failure. Despite recent advances in therapeutic approaches using prostanoids, endothelin antagonists, and so on, PAH remains a challenging condition. To develop a novel therapeutic approach, we have established a nonviral gene delivery system of poly(ethylene glycol) (PEG)-based block catiomers, which form a polyplex nanomicelle with a nanoscaled core–shell structure in t...

  8. Variability in hemodynamic evaluation of pulmonary hypertension at large referral centers

    OpenAIRE

    Pugh, Meredith E.; Hemnes, Anna R.; Trammell, Aaron; Newman, John H.; Robbins, Ivan M.

    2014-01-01

    Despite consensus guidelines for right heart catheterization (RHC) in the diagnosis of pulmonary arterial hypertension (PAH), considerable differences exist in the performance of RHC, interpretation of hemodynamic data, and frequency of RHC performance in patients with established disease. These differences may lead to variability in diagnosis or treatment of PAH. We sought to gather information on the standard practice of RHC for the diagnosis and management of PAH from experienced pulmonary...

  9. Variability of arterial blood pressure in normal and hypertensive pregnancy.

    Science.gov (United States)

    Oney, T; Meyer-Sabellek, W

    1990-12-01

    In normal pregnancy the circadian blood pressure rhythm is similar to that in the non-pregnant state, with the highest blood pressure values in the morning and the lowest at midnight. This rhythm is lost in patients with pre-eclampsia. Women with severe pre-eclampsia show a reversed circadian rhythm, with a nocturnal increase in blood pressure during the sleeping phase. Although the reasons for this nocturnal hypertension in severe pre-eclampsia are poorly understood, the results suggest that pre-eclamptic women are endangered by hypertensive emergencies, mostly at night. Therefore blood pressure measurement should be extended to the night, and antihypertensive treatment must be adapted to the demands of a reversed circadian rhythm in relevant subgroups of patients. PMID:2082002

  10. Pharmacodynamic and pharmacoeconomic aspects of application of antihypertensive preparations of various groups in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Kurkina T.V.

    2010-09-01

    Full Text Available At the background of the therapy for 3 months with Perindopril, Telmisartan and Bisoprolol, the patients with arterial hypertension were noted to decrease systolic and diastolic arterial pressure. The preparations under investigation had different effects on electrolyte metabolism. Therapy with Telmisartan turned out to have the least effect on electrolyte metabolism. Microalbuminuria is a risk factor in patients with arterial hypertension and may influence on the basic blood electrolyte balance. Bisoprolol should be recommended as the most preferable therapy for arterial hypertension from the pharmacoeconomic point of view. In order to control morning systolic arterial pressure the preference should be given to Perindopril, while for controlling evening systolic arterial pressure the preference should be given to Telmisartan

  11. From arterial hypertension complications to von Hippel-Lindau syndrome diagnosis.

    Science.gov (United States)

    Kozaczuk, Sylwia; Ben-Skowronek, Iwona

    2015-01-01

    Von Hippel-Lindau syndrome is a rare, genetically based, autosomal dominant disorder. Its course is accompanied by the development of multiple neoplasms with the following tumours diagnosed most commonly in the central nervous system haemangioblastoma, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, and endolymphatic sac tumours. Additionally, renal and pancreatic cystadenomas and epididymal cystadenomas have been diagnosed in males and cystadenomas of the broad ligament of the uterus have been diagnosed in females.The following paper presents the diagnostic way in a boy with vision disorders as the first symptom. Hypertension retinopathy and extremely elevated blood pressure were observed during ophthalmologic consultation. Complications of arterial hypertension were confirmed by echocardiography, which diagnosed hypertension cardiomyopathy. Hypertension retinopathy was confirmed by optical coherence tomography. Examinations performed in the neurology, cardiology, and finally endocrinology indicated a bilateral phaeochromocytoma as the cause of arterial hypertension. Moreover, some genetic investigations showed a mutation in the VHL ex.1 p.Y112 C gene responsible for the hereditary form of phaeochromocytoma which confirmed von Hippel-Lindau syndrome. After surgical treatment of phaeochromocytoma the patient needed careful management according to the surveillance protocol for von Hippel-Lindau disease. PMID:26268347

  12. 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. PMID:26953075

  13. 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.

  14. Effects of CPAP on "vascular" risk factors in patients with obstructive sleep apnea and arterial hypertension

    Directory of Open Access Journals (Sweden)

    Litvin AY

    2013-05-01

    Full Text Available AY Litvin,1 ZN Sukmarova,1 EM Elfimova,1 AV Aksenova,1 PV Galitsin,1 AN Rogoza,2 IE Chazova11Department of Systemic Hypertension, 2Department of New Methods of Diagnostics, Russian Cardiology Research and Production Complex, Ministry of Health, Moscow, Russian FederationBackground: The aim of this study was to assess the effects of continuous positive airway pressure (CPAP on arterial stiffness, central blood pressure, and reflected pulse wave characteristics in patients with severe obstructive sleep apnea (OSA and stage 2–3 arterial hypertension.Methods: Forty-four patients with hypertension and severe OSA (apnea/hypopnea index > 30 received stepped dose titration of antihypertensive treatment, consisting of valsartan 160 mg + amlodipine 5–10 mg + hydrochlorothiazide 25 mg. CPAP therapy was added after 3 weeks of continuous antihypertensive treatment with BP 12 msec persisted in 35% of patients on antihypertensive treatment and effective CPAP, in 56% of patients on antihypertensive treatment alone, and in 53% of patients on placebo CPAP. Only the combination of antihypertensive treatment with effective CPAP achieved a significant reduction in augmentation index and AASI, along with a further reduction in aortic and brachial BP.Conclusion: Effective CPAP for 3 weeks resulted in a significant additional decrease in office BP, ambulatory BP monitoring, central BP, and augmentation index, together with an improvement in arterial stiffness parameters, ie, cfPWV and AASI, in a group of hypertensive patients with OSA.Keywords: antihypertensive therapy, hypertension, obstructive sleep apnea, continuous positive airway pressure, blood pressure, arterial stiffness, pulse wave velocity

  15. Arterial wall stiffness in patients with essential hypertension at young age

    Directory of Open Access Journals (Sweden)

    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.

  16. Pathological observation of brain arteries and spontaneous aneurysms in hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate the role of hypertension in the pathogenesis of cerebral aneurysms in rats.Methods Twenty spontaneous hypertensive rats (SHR) and 10 Wistar-Kyoto rats (WKY) were included in this observational study. Animals were fed with normal diet and drinking water. No experimental modifications were undertaken in either group. They were sacrificed at one year of age, the bifurcations of the circle of Willis were dissected and longitudinal serial sections were prepared for light microscopic and transmission electron microscopic study.Results In the SHR group, 2 of the 20 rats formed an aneurysm respectively at the bifurcations of the basilar artery. As revealed by electron microscopy, injury at the bifurcation of the artery first occurred on the steeper side of the intimal pad. Furthermore, loss of endothelial cells, small depressions on the intima, disruptive internal elastic lamina and lymphocytes or red blood cells infiltration were noted at the steeper side of the intimal pad. No significant changes were observed in WKY group.Conclusions Cerebral aneurysms can form spontaneously in SHR without ligation of the common carotid artery and without a diet containing β-aminoproprionitrile. Long-standing systemic arterial hypertension is one of the etiological factors that contributes to aneurysm formation in SHR rats.

  17. Impact of Intra-Extracranial Hemodynamics on Cerebral Ischemia by Arterial Hypertension (Part 2

    Directory of Open Access Journals (Sweden)

    Alexander G. Kruglov, PhD, ScD

    2012-06-01

    Full Text Available The association between hemodynamic and biochemical parameters of cerebral blood flow have been studied in man, using mathematical methods of statistics. The values have been obtained through catheterization using a probe jammed at the level of the bulb of the superior jugular vein. Relationships with central hemodynamic parameters have been evaluated, including the right atrium, the right ventricle, and the left ventricle, as well as with pressure and biochemical values of the arterial bed. Data have been acquired in patients with stable arterial hypertension. Analysis of all relationship between hemodynamic and biochemical parameters has shown that the uniform hemodynamic zone: Sin.P. – SJV – SEV – the right atrium, normally participates in regulation of gaseous exchange in the human brain depending on the minimum pressure on the way of outflow from the brain. In stable arterial hypertension, this type of regulation is lost. On the basis of the results of this study, it has been concluded that blood viscosity is normally a primary controlled parameter of homeostasis. In stable arterial hypertension, homeostatic control of factors determining rheological and thrombogenic properties of blood, as well as participating in the development of brain ischemic conditions is lost. This increases risk of disturbances in central hemodynamics.

  18. Impact of Intra-Extracranial Hemodynamics on Cerebral Ischemia by Arterial Hypertension (Part 1

    Directory of Open Access Journals (Sweden)

    Alexander G. Kruglov, PhD, ScD

    2012-06-01

    Full Text Available The present study was conducted to examine the interaction of biochemical parameters within the blood flow, their effect on the cerebral blood flow, as well as the mechanisms of cerebral ischemia by stable arterial hypertension. The hemodynamics and biochemical indicators of cerebral blood flow without the additives of the extracranial blood were obtained by the catheterization method via a probe wedged at the level of the bulb of the superior jugular vein. Sampling of the arterial blood was done in the thoracic aorta. Correlation and factor analysis of the relationship of the biochemical substances within the blood flow, and of the hemodynamic indicators of the cerebral inflow and outflow of blood were conducted by stable arterial hypertension compared with similar data of the control group. The differences thus identified led to the conclusion that by stable arterial hypertension, there is a loss of the homeostatic control of the factors determining the rheological and thrombogenic properties of the blood involved in the formation of cerebral ischemic events.

  19. Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

    Science.gov (United States)

    Jimenez, Sergio A; Piera-Velazquez, Sonsoles

    2016-04-01

    Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed. PMID:26807760

  20. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Kjel [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: kjel_andersen@web.de; Hennersdorf, Marcus [Department of Cardiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: hennersdorf@med.uni-duesseldorf.de; Cohnen, Mathias [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: cohnen@med.uni-duesseldorf.de; Blondin, Dirk [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: blondin@med.uni-duesseldorf.de; Moedder, Ulrich [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: moedder@uni-duesseldorf.de; Poll, Ludger W. [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: poll@gmx.de

    2009-07-15

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  1. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    International Nuclear Information System (INIS)

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  2. Transforming growth factor-β inhibition attenuates pulmonary arterial hypertension in rats

    OpenAIRE

    Megalou, Aikaterini J; Glava, Chryssoula; Oikonomidis, Dimitrios L.; Vilaeti, Agapi; Agelaki, Maria G; Baltogiannis, Giannis G.; Papalois, Apostolos; Vlahos, Antonios P.; Kolettis, Theofilos M

    2010-01-01

    The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the effects of T9429, an antibody against transforming growth factor-β receptors, on hemodynamic, histological and functional parameters in the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats (268±10g) via an osmotic mini-pump ...

  3. Risk factors related to systemic arterial hypertension in victims of cerebral vascular accident

    OpenAIRE

    Joselany Áfio Caetano; Verineida Lima; Enedina Soares; Zélia Maria de Sousa Araújo Santos

    2006-01-01

    The Cerebrovascular accident (AVC)is the third cause of death in the world.Apart systemic arterial hypertension (HAS),many other preventable factors are related to its appearance and evolution.This study aimed at identifying the risk factors for AVC in interned hypertensive patients.It was a descriptive study held at a philanthropic hospital in Sobral-Ceará,with fourteen patients taken ill with AVC.Among those,85.7%(n=12)were above 65 years old and the same quantitative were retired;71,4%(n=1...

  4. COMPARATIVE EVALUATION OF HEMODYNAMIC CHARACTERISTICS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Y. E. Teregulov

    2015-09-01

    Full Text Available Aim. To study the peculiarities of hemodynamic disorders in patients with rheumatoid arthritis (RA and arterial hypertension (HT, and in patients with hypertension but without RA using the integral indicators of arterial stiffness.Material and methods. The study included 106 RA patients (group 1, among them 83 (78% women and 23 (22% men, mean age 45.3±10.3 years. The group of comparison (group 2 included 63 patients (22 (35% women and 41 (65% men, mean age 47.9±12.8 years with HT stages 1-3. The control group (group 3 consisted of 32 healthy volunteers: 19 women and 13 men, mean age 24.7±5.34 years. All patients underwent ECG and echocardiography. The model of cardiovascular system was used to calculate the modulus of volume elasticity (MVE, mean arterial blood pressure (BP and total peripheral vascular resistance (TPR; stroke volume and cardiac output were measured using echocardiography.Results. Significant differences in the parameters of BP, arterial stiffness and TPR were identified in patients with RA and HT as compared with the patients of the control group. Arterial stiffness in RA patients with HT, as well as without it, was significantly higher and TPR was lower than in hypertensive patients. RA patients with HT were older and had significantly higher values of cardiac output than those without HT. In RA patients hyperkinetic type of hemodynamics was observed in 53.8% of the cases, eukinetic - in 34.9%, hypokinetic - in 11.3%. Hypertensive patients had same types of hemodynamics in 3.2%, 61.9%, and 34.9%, respectively. In healthy people hyperkinetic type was observed in 22.9% of the cases, eukinetic - in 65.6%, hypokinetic - in 12.5%.Conclusions. RA patients as compared with healthy people had significantly higher arterial stiffness indices regardless of BP. At that, hyperkinetic type of hemodynamics prevailed in RA patients, while in hypertensive patients and healthy people - the eukinetic one. Increased stroke volume and cardiac

  5. [Pathophysiology of left ventricular hypertrophy in arterial hypertension].

    Science.gov (United States)

    Vallotton, M B; Braconi-Quintaje, S; Lang, U

    1997-02-11

    The role of left ventricular hypertrophy as an independent risk factor for subsequent cardio-vascular events is well established, therefore the authors, in this brief review, describe the endocrine function of the heart and the role played by various factors, including hormones, in the development of cardiac remodeling during the course of hypertension. They then outline the present state of our knowledge concerning transmembrane signaling in the cardiomyocyte in response to an activation of specific receptors for vasoactive hormones of the renin-angiotensin II-aldosterone system. PMID:9139339

  6. Cambios en el pronóstico a largo plazo de la hipertensión arterial pulmonar Changes long term prognosis of 17 patients with pulmonary artery hypertension

    Directory of Open Access Journals (Sweden)

    Andrés Enríquez

    2011-03-01

    Full Text Available Background: Pulmonary artery hypertension (PAH is a progressive disease with high mortality. Major advances had been made in the treatment of this condition during the last decade. Aim: To characterize the clinical evolution and mortality of a cohort of Chilean patients. Material and Methods: Seventeen patients with PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled. Measurements at diagnosis included hemodynamic variables and 6-minute walk test. The patients were followed clinically for 3 years and the observed mortality was compared with that predicted by the prognostic equation proposed by the historic registry of the National Institutes of Health (NIH. Results: The mean age of patients was 45 years and 80% had an idiopathic PAH. The mean median pulmonary artery pressure was 57 ± 15 mmHg, the cardiac index was 2.4 ± 0.7 l/min/m² and the right atrial pressure was 12 ± 8 mmHg. The 6-minute walk distance was 348 ± 98 m. All patients received anticoagulants. Eighty two percent received ambrisentan, 12% received bosentan, 29% received iloprost and 24% sildenafil. At the end of follow-up only 3 patients had died, with an observed survival rate of88, 82 and 82% at 1, 2 and 3 years, respectively. In contrast, the survival calculated according to the predictive formula of the NIH was 67, 56 and 45%, respectively. Among surviving patients, an improvement in exercise capacity was observed after one year (p < 0.05. Conclusions: The observed survival rate was significantly better than that estimated according to historical data. Furthermore, therapy was associated with an improvement in functional capacity after one year. This prognostic improvement is consistent with data of other contemporary registries published after the NIH Registry.

  7. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    Science.gov (United States)

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, PFMD; control: r=-0.735, PFMD: 5.92±1.43% versus 7.73±1.31%, PFMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID:26202692

  8. Renal dysfunction and state of metabolic and hemodynamic factors in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Klochkov V.A.

    2011-12-01

    Full Text Available The aim of the investigation is to carry out comparative evaluation of metabolic and hemodynamic indices in patients with arterial hypertension (AH and renal dysfunction; to study the interrelation between arterial blood pressure level normalization and the presence or lack of microalbuminuria (MAU in the morning urine portion of patients with AH after therapy with antihypertensive preparations (APs of various groups. Methods. 121 persons have been investigated, 91 out — patients of both sexes, aged 33-55, with the diagnosis of arterial hypertension of stage II risk III, who have been taking Perindopril, Telmisartan and Bisoprolol for3 months. The control of arterial pressure level, biochemical analysis of metabolic indices and morning urine portion test for microalbuminuria has been carried out. Results. MAU has been revealed in 17,6% patients, occurring more frequently in men than in women. Microalbuminuria is accompanied by reliable decrease of total and ionized calcium and magnesium concentrations, an increase of potassium level in blood plasma, increase of cholesterol, triglycerides, glucose and levels. Patients with AH and renal dysfunction reliably demonstrate higher levels of systolic and diastolic arterial pressure in the morning and evening hours, their normalization effect after APs intake is significantly interconnected with MAU presence. Conclusion. In patients with AH and MAU the main risk factors of cardio-vascular diseases development are more expressed. Microalbuminuria is a risk factor in patients with arterial hypertension and may influence on the basic blood electrolyte balance. While carrying out antihypertensive therapy the presence of MAU should be taken into consideration

  9. Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

    OpenAIRE

    Lee Dongwon; Wu Dongmei; Sung Yong

    2011-01-01

    Abstract There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biolo...

  10. Effect of Cardio-Metabolic Risk Factors Clustering with or without Arterial Hypertension on Arterial Stiffness: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Vasilios G. Athyros

    2013-11-01

    Full Text Available The clustering of cardio-metabolic risk factors, either when called metabolic syndrome (MetS or not, substantially increases the risk of cardiovascular disease (CVD and causes mortality. One of the possible mechanisms for this clustering's adverse effect is an increase in arterial stiffness (AS, and in high central aortic blood pressure (CABP, which are significant and independent CVD risk factors. Arterial hypertension was connected to AS long ago; however, other MetS components (obesity, dyslipidaemia, dysglycaemia or MetS associated abnormalities not included in MetS diagnostic criteria (renal dysfunction, hyperuricaemia, hypercoaglutability, menopause, non alcoholic fatty liver disease, and obstructive sleep apnea have been implicated too. We discuss the evidence connecting these cardio-metabolic risk factors, which negatively affect AS and finally increase CVD risk. Furthermore, we discuss the impact of possible lifestyle and pharmacological interventions on all these cardio-metabolic risk factors, in an effort to reduce CVD risk and identify features that should be taken into consideration when treating MetS patients with or without arterial hypertension.

  11. Pathogenesis of Focal Cytoplasmic Necrosis of the Smooth Muscle Cells in Hypertensive Rat Arterial Media

    International Nuclear Information System (INIS)

    Hypertensive rat arteries exhibited severe medial smooth muscle cell injury and necrosis. Electron microscopic observations showed the smooth muscle cells of these arteries exhibited characteristics of focal cytoplasmic necrosis forming new cytodemarcating membrane between the healthy cytoplasm and necrotic cytoplasm. When the focal necrotic cytoplasm disappeared from the injured smooth muscle cells, it left it with a moth-eaten leaf-like appearance (moth-eaten necrosis). At an advanced stage of injury, smooth muscle cells changed to islet-like cell bodies with newly formed basement membranes around them, and further islet-like cell bodies and cell debris disappeared leaving lamellar and reticular basement membranes. In hypertensive rats injected with nitroblue tetrazolium (NBT), formazan deposits were observed in the medial cells and nitrotyrosine, a biomarker of peroxynitrite, were immunohistochemically observed in the arterial media. Nick-end positive extranuclear small granular bodies, which might have derived from focal necrotic cytoplasm and nucleus, were detected in the arterial media using DNA nick-end labeling method. Based on electron microscopical and histochemical findings, we conjectured that the focal cytoplasmic necrosis of the smooth muscle cells in the arterial media depended on injury arising from mitochondria-derived oxidants

  12. 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......, the capillaries in the germinal matrix are not supported by firm glial structures. Arterial pressure rises are therefore likely to be responsible for germinal matrix haemorrhage in the premature neonate, and the risk of haemorrhage probably diminishes as autoregulation of cerebral blood-flow is...

  13. IMPLEMENTATION OF BIOFEEDBACK IN A CLOSED LOOP OF HEART RATE VARIABILITY AND PACED BREATHING IN PATIENTS WITH ARTERIAL HYPERTENSION

    OpenAIRE

    Kulik, O.; Schmidt, O; BELAL S. A. S.; Rank, I.

    2014-01-01

    The effectiveness of biofeedback in a closed loop of heart rate variability (HRV) and paced breathing in patients with arterial hypertension was studied. 61 subjects with arterial hypertension (31 females and 30 males, mean age 56.8 ± 6.2 years) were examined. In accordance with the objective of the study all subjects were divided into 2 groups: 1 biofeedback group (34 subjects) and 2 the comparison group (27 subjects). 5 biofeedback sessions were performed in biofeedback group. In the compar...

  14. Self-care practice of patients with arterial hypertension in primary health care

    Directory of Open Access Journals (Sweden)

    Cláudia Rayanna Silva Mendes

    2016-02-01

    Full Text Available Objective: to evaluate the practice of self-care performed by patients with systemic arterial hypertension in primary health care. Methods: this is a descriptive and cross-sectional study, conducted with 92 individuals with arterial hypertension in a primary care unit. The data collection occurred through script and data analyzed using descriptive statistics (frequency, mean and standard deviation and through the understanding of the adaption between capacity and self-care demand. Results: it was identified as a practice of self-care: adequate water intake, salt intake and restricted coffee, satisfactory sleep period, abstinence from smoking and alcoholism, continuing pharmacological treatment and attending medical appointments. As the demands: inadequate feeding, sedentary lifestyle, had no leisure activities, self-reported stress, and limited knowledge. Conclusion: although patients performed treatment a few years ago, still showed up self-care deficits, highlighting the need for nurses to advise and sensitize about the importance of self-care practice.

  15. Prevalence of renal artery stenosis in subjects with moderate hypertension. A population-based study

    DEFF Research Database (Denmark)

    Andersen, Ulrik B; Borglykke, Anders; Jørgensen, Torben

    2011-01-01

    Abstract Aim. To examine the prevalence of significant renal artery stenosis (RAS) in subjects with moderate to severe hypertension. Materials and methods. Subjects aged 50-66 years with blood pressure >160/100 mmHg or receiving antihypertensive treatment were selected from the population study...... balloon angioplasty. Two patients had reduced size and function of the affected kidney. Among the non-invasively treated patients, one showed stenosis progression at the 2-year follow-up examination. Conclusion. In subjects aged 50-66 years with hypertension grade II-III, RAS is rare among men, but not...... among women. These women may suffer from fibromuscular dysplasia. They are at risk of losing kidney function and developing severe hypertension, but they would not have been considered for screening according to present criteria....

  16. METABOLIC DISTURBANCES IN THE FUTURE DEVELOPMENT AND PROGRESSION OF ARTERIAL HYPERTENSION IN YOUNG MEN

    Directory of Open Access Journals (Sweden)

    A. V. Gordienko

    2015-01-01

    Full Text Available Objective: to reveal carbohydrate and lipid metabolic disturbances and their possible importance in examined young men with early arterial hypertension (AH. Subjects and methods. A total of 130 men aged 40.3 ± 4.3 years were examined. There were 3 patient groups: stage I hypertensive disease with a history of AH (n = 61; primarily diagnosed hypertensive disease without evidence of long-term AH (n = 39; a control group noncardiovascular diseases (n = 30. Results. The patients with long-term AH were more commonly found to have a compromised history of cardiovascular diseases and type 2 diabetes mellitus, signs of insulin resistance and subclinical atherosclerosis than those with the primarily diagnosed disease and the control group. Conclusion. Carbohydrate and lipid metabolic disturbances are latent in young men with long-term AH. Both 2and 1-hour oral glucose tolerance tests are recommended for the early diagnosis of glycemic disorders in the above patient cohort. 

  17. Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.

    OpenAIRE

    Morelli, S.; Ferri, C; Di Francesco, L; Baldoncini, R; Carlesimo, M; Bottoni, U; Properzi, G; Santucci, A.

    1995-01-01

    OBJECTIVES--To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS--Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 w...

  18. Pulmonary artery denervation for treatment of a patient with pulmonary hypertension secondary to left heart disease

    OpenAIRE

    Zhang, Hang; Zhang, Juan; Xie, Du-Jiang; Jiang, Xiaoming; Zhang, Feng-Fu; Chen, Shao-Liang

    2016-01-01

    Pulmonary hypertension (PH) predicts poor outcome in patients with left heart disease. A 62-year-old man was referred for heart failure associated with ischemic cardiomyopathy. He received a diagnosis of combined postcapillary and precapillary PH secondary to left heart disease on the basis of hemodynamic parameters. After the pulmonary artery denervation procedure was performed, hemodynamic parameters were markedly improved, which resulted in a significant increase in functional capacity.

  19. Significance of Microcirculation Abnormalities as Counter-hypotension Mechanism in Essential Arterial Hypertension

    OpenAIRE

    Vl V Shkarin; М.V. Lozhakova

    2011-01-01

    The aim of the investigation is to study the contribution of microcirculation abnormalities to “escape effect” development in drug antihypertensive therapy in patients with essential arterial hypertension (AH). Materials and Methods. There were examined 107 patients with essential AH of the I–II severity degree (49 males, 58 females; their mean age being 48.9±9.9 years). In all patients before and after 8 weeks of drug antihypertensive therapy there was carried out ambulatory blood pressu...

  20. Computational Simulation of the Pulmonary Arteries and its Role in the Study of Pediatric Pulmonary Hypertension

    OpenAIRE

    Hunter, Kendall S.; Feinstein, Jeffrey A.; Ivy, D. Dunbar; Shandas, Robin

    2010-01-01

    The hemodynamic state of the pulmonary arteries is challenging to routinely measure in children due to the vascular circuit's position in the lungs. The resulting relative scarcity of quantitative clinical diagnostic and prognostic information impairs management of diseases such as pulmonary hypertension, or high blood pressure of the pulmonary circuit, and invites new techniques of measurement. Here we examine recent applications of macro-scale computational mechanics methods for fluids and ...

  1. Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension

    OpenAIRE

    Dubin, Ruth; Owens, Christopher; Gasper, Warren; Ganz, Peter; Johansen, Kirsten

    2011-01-01

    Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothe...

  2. A case of malignant catatonia with idiopathic pulmonary arterial hypertension treated by electroconvulsive therapy

    OpenAIRE

    Hobo, Mizue; Uezato, Akihito; Nishiyama, Mitsunori; Suzuki, Mayumi; Kurata, Jiro; Makita, Koshi; Yamamoto, Naoki; Nishikawa, Toru

    2016-01-01

    Background Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal cardiovascular disease if left untreated. In patients with IPAH with psychiatric illness or other complications, careful attention is required when administering medical therapies that may affect their hemodynamics. Patients suffering from IPAH who undergo anesthesia and surgery have a high mortality and morbidity rate. We describe the treatment of intractable psychiatric symptoms with electroconvulsive th...

  3. Relationship Between Carotid Artery Calcification Detected in Dental Panoramic Images and Hypertension and Myocardial Infarction

    International Nuclear Information System (INIS)

    Carotid artery calcification may be related to cerebrovascular accident, which may result in death or physical and mental disabilities in survivors. Our purpose is to study the association of carotid artery calcification (CAC) on dental panoramic radiographs and two risk factors of cerebrovascular accident (CVA) including hypertension and myocardial infarction (MI). Panoramic images of 200 patients that were all women above 50 years of age (a population suffering from vascular diseases) were investigated. All panoramic images were provided under similar conditions in terms of the type of panoramic radiograph equipment, type of applied films and the automatic film processor. Then, the patients answered questions about MI history and taking antihypertensive drugs. We also measured the blood pressure of patients in two separate surveys. Data analysis was performed by SPSS statistical program. We used Exact Fisher test and Chi-Square test at a significant level of less than 0.05 to study the effect of these variables on the occurrence of carotid artery calcification. Among 200 studied samples, 22 of the patients (11%) had carotid artery calcification on the dental panoramic radiograph. In total, 52 patients (26%) had hypertension and four people (2%) had a history of MI. Eleven individuals among patients suffering from hypertension (21.2%) and three individuals among patients with a history of MI (75%) demonstrated CAC on dental panoramic images . The relationship between CAC found on dental panoramic radiographs and two CVA risk factors--hypertension and MI-- was significant. Therefore, it seems that detection of CAC on panoramic images of dental patients must be considered by dentists

  4. Hemodynamic and Histologic Characterization of a Swine (Sus scrofa domestica) Model of Chronic Pulmonary Arterial Hypertension

    OpenAIRE

    Rothman, Abraham; Wiencek, Robert G; Davidson, Stephanie; William N. Evans; Restrepo, Humberto; Sarukhanov, Valeri; Rivera-Begeman, Amanda; Mann, David

    2011-01-01

    The purpose of this work was to develop and characterize an aortopulmonary shunt model of chronic pulmonary hypertension in swine and provide sequential hemodynamic, angiographic, and histologic data by using an experimental endoarterial biopsy catheter. Nine Yucatan female microswine (Sus scrofa domestica) underwent surgical anastomosis of the left pulmonary artery to the descending aorta. Sequential hemodynamic, angiographic, and pulmonary vascular samples were obtained. Six pigs (mean weig...

  5. Pulmonary Vascular Capacitance as a Predictor of Vasoreactivity in Idiopathic Pulmonary Arterial Hypertension Tested by Adenosine

    OpenAIRE

    Shafie, Davood; Dohaei, Abolfazl; AMIN, Ahmad; Taghavi, Sepideh; Naderi, Nasim

    2015-01-01

    Background: Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH). Pulmonary arteriolar capacitance (Cp) approximated by stroke volume divided by pulmonary pulse pressure (SV/PP) is considered as an independent predictor of mortality in patients with IPAH. Objectives: We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested...

  6. Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension

    OpenAIRE

    Valerio, Christopher J; Peter Kabunga; Coghlan, John G.

    2009-01-01

    Three different classes of specific therapy exist for pulmonary arterial hypertension. Ambrisentan belongs to the endothelin receptor antagonist (ERA) class of drugs, which inhibit the action of Endothelin-1; a potent vasoconstrictor and mitogen. Unlike bosentan and sitaxentan, it has a propanoic-acid based structure and like sitaxentan it has selective affinity for type A Endothelin receptors. Two large randomized controlled trials (ARIES-1 and ARIES-2) have demonstrated clinical benefit wit...

  7. The relationship between occupational exposure to lead and manifestation of cardiovascular complications in persons with arterial hypertension

    International Nuclear Information System (INIS)

    The chronic exposure to lead represents a risk factor of arterial hypertension development. Ambulatory blood pressure monitoring is the most prognostically reliable method of measuring of arterial blood pressure. The study is aimed at evaluating the relationship between occupational exposure to lead and manifestation of cardiovascular complications in patients with arterial hypertension. The studies included 73 men (mean age, 54.26 ± 8.17 years) with arterial hypertension, treated with hypotensive drugs: group I-persons occupationally exposed to lead (n = 35) and group II-individuals not exposed to lead (n = 38). An analysis of results obtained during ambulatory blood pressure monitoring disclosed significantly higher values of mean systolic blood pressure, mean blood pressure, pulse pressure, and variability of systolic blood pressure in the group of hypertensive patients occupationally exposed to lead as compared to patients with arterial hypertension but not exposed to lead. The logistic regression showed that a more advanced age, higher concentration of blood zinc protoporphyrin, and a higher mean value of pulse pressure represented independent risk factors of left ventricular hypertrophy in the group of persons with arterial hypertension and chronically exposed to lead (ORage = 1.11; ORZnPP = 1.32; ORPP = 1,43; p < 0.05). In view of the above data demonstration that occupational exposure to lead represents an independent risk factor of increased pulse pressure may be of key importance in the process of shaping general social awareness as to harmful effects of lead compounds on human health.

  8. Arterial pulmonary hypertension in noncardiac intensive care unit

    OpenAIRE

    Tsapenko, Mykola

    2008-01-01

    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 elev...

  9. Home-made fenestrated amplatzer occluder for atrial septal defect and pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Fabio Dell'Avvocata; Gianluca Rigatelli; Paolo Cardaioli; Massimo Giordan

    2011-01-01

    We report the management of a patient with secundum atrial septal defect (ASD)and severe pulmonary hypertension.A 65-year-old male with recently diagnosed atrial serital defect was referred to our centre for decompensated right heart failure with rest and exercise induced dispnea and severe pulmonary hypertension.Right heart catheterization confirmed a mean pulmonary pressure of about 55 mmHg and a Qp/Qs of 2.7.An occlusion test with a compliant large balloon demonstrated partial fall of pulmonary arterial pressure.The implantation of a home-made fenestrated Amplatzer ASD Occluder (ASO) was planned in order to decrease lefttoright shunt and promote further decrease of pulmonary arterial pressure in the long-term.Thus,by means of mechanical intracardiac echocardiography study with a 9F 9 MHz Ultralce catheter(Boston Scientific Corp.),we selected a 34 mm ASO for implantation.Four millimeter fenestration was made inflating a 4 ntm non-compliant coronary balloon throughout the waist of the ASO,which was successfully implanted under intracardiac echocardiography.After six months,a decrease of pulmonary arterial pressure to 24 mmHg and full compensated right heart failure was observed on transthoracic echocardiography and clinical examination.This case suggests that transcatheter closure with home-made fenestrated ASD in elderly patients with severe pulmonary hypertension is feasible.

  10. Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

    Directory of Open Access Journals (Sweden)

    K.L. Bessa

    2011-08-01

    Full Text Available This study was designed to evaluate the effect of drag reducer polymers (DRP on arteries from normotensive (Wistar and spontaneously hypertensive rats (SHR. Polyethylene glycol (PEG 4000 at 5000 ppm was perfused in the tail arterial bed with (E+ and without endothelium (E- from male, adult Wistar (N = 14 and SHR (N = 13 animals under basal conditions (constant flow at 2.5 mL/min. In these preparations, flow-pressure curves (1.5 to 10 mL/min were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7%, WSS (Wistar/E+: 36; SHR/E+: 40% and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

  11. [Clinical guidelines for detection, prevention, diagnosis and treatment of systemic arterial hypertension in Mexico (2008)].

    Science.gov (United States)

    Rosas, Martín; Pastelín, Gustavo; Vargas-Alarcón, Gilberto; Martínez-Reding, Jesús; Lomelí, Catalina; Mendoza-González, Celso; Lorenzo, José Antonio; Méndez, Arturo; Franco, Martha; Sánchez-Lozada, Laura Gabriela; Verdejo, Juan; Sánchez, Noé; Ruiz, Rocío; Férez-Santander, Sergio Mario; Attie, Fause

    2008-01-01

    The multidisciplinary Institutional Committee of experts in Systemic Arterial Hypertension from the National Institute of Cardiology "Ignacio Chávez" presents its update (2008) of "Guidelines and Recommendations" for the early detection, control, treatment and prevention of Hypertension. The boarding tries to be simple and realistic for all that physicians whom have to face the hypertensive population in their clinical practice. The information is based in the most recent scientific evidence. These guides are principally directed to hypertensive population of emergent countries like Mexico. It is emphasized preventive health measures, the importance of the no pharmacological actions, such as good nutrition, exercise and changes in life style, (which ideally it must begin from very early ages). "We suggest that the changes in the style of life must be vigorous, continuous and systematized, with a real reinforcing by part of all the organisms related to the health education for all population (federal and private social organisms). It is the most important way to confront and prevent this pandemic of chronic diseases". In this new edition the authors amplifies the information and importance on the matter. The preventive cardiology must contribute in multidisciplinary entailment. Based mainly on national data and the international scientific publications, we developed our own system of classification and risk stratification for the carrying people with hypertension, Called HTM (Arterial Hypertension in Mexico) index. Its principal of purpose this index is to keep in mind that the current approach of hypertension must be always multidisciplinary. The institutional committee of experts reviewed with rigorous methodology under the principles of the evidence-based medicine, both, national and international medical literature, with the purpose of adapting the concepts and guidelines for a better control and treatment of hypertension in Mexico. This work group recognizes

  12. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial

    OpenAIRE

    Ehlken, Nicola; Lichtblau, Mona; Klose, Hans; Weidenhammer, Johannes; Fischer, Christine; Nechwatal, Robert; Uiker, Sören; Halank, Michael; Olsson, Karen; Seeger, Werner; Gall, Henning; Rosenkranz, Stephan; Wilkens, Heinrike; Mertens, Dirk; Seyfarth, Hans-Jürgen

    2016-01-01

    AIMS: The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. METHODS AND RESULTS: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (...

  13. Prevalence of hypertension among obese and non-obese patients with coronary artery disease

    International Nuclear Information System (INIS)

    Background: Globally, obesity is now recognised as an epidemic. The degree of obesity is proportional to the rate of development of cardiovascular diseases, hence, resulting in a dramatic increase in morbidity and mortality. Apart from obesity, hypertension is another well recognised risk factor contributing to coronary artery disease (CAD). The precise prevalence of obesity-related hypertension varies with age, race and gender; and is yet unknown in our population. The objective of this study was to determine the prevalence of hypertension in obese and non-obese patients with diagnosed CAD. Methods: This hospital based descriptive study was conducted in Cardiology Department of Postgraduate Medical Institute, Lady Reading Hospital, Peshawar from March 15, 2007 to May 30, 2008. A total of 200 patients with diagnosed CAD were enrolled, 100 were found obese and 100 non-obese. Results: Among these, a total of 111 (55.5%) were found to be hypertensive, 66 (59.46%) of these were obese and 45 (40.54%) non-obese (p=0.003). Conclusion: Obese patients with CAD had significantly more frequent hypertension. (author)

  14. Cognitive disorders in patients with arterial hypertension in real medical practice

    Directory of Open Access Journals (Sweden)

    Khomazyuk T.A.

    2015-06-01

    Full Text Available There was analyzed the extent and structure of cognitive disorders in outpatient conditions by the data of examination of 118 hypertension patients stage II with arterial hypertension of 1-2 degrees, which were under the supervision of General Practitioners. Neuropsychological examination was carried out by MMSE (Mini-Mental State Examination and FAB (Frontal Assessment Battery scales, verbal memory was studied by the method of Luria, concentration and speed of sensorimotor reactions - by techniques of Schulte and Rybakov. It was found that 28.8% of patients had cognitive disorders, mainly of neurodynamic nature, in particular, the ability of concentration and speed of psychomotor reactions was reduced. The presence of verbal memory disorders of varying severity associated with hypertension was revealed. Analysis of medical records testifies to the absence of attention to this issue in rehabilitation programs of hypertensive patients at the primary stage of care. The importance of timely diagnosis of cognitive disorders as a marker of early disorders of cerebral circulation and the functional state of the brain, the target organ in hypertension of 1-2 degrees was demonstrated.

  15. Correlation of arterial stiffness index with carotid atherosclerosis in patients with primary hypertension

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Cai; Li-Min Li; Xue-Min Wang; Cui-Qing Sun; Hai-Wei Zhao; Hui Wang; Rui-Chao Liu

    2016-01-01

    Objective:To explore the correlation of arterial stiffness index with carotid atherosclerosis in patients with primary hypertension.Methods:A total of 86 patients with primary hypertension who were admitted in our hospital from January, 2013 to September, 2015 were included in the study, and divided into the carotid atherosclerosis group (IMT≥0.9 mm, with plaque being detected) and the pure hypertension group (normal IMT) according to the carotid artery color Doppler ultrasound results. According to the ambulatory blood pressure monitoring results, the carotid atherosclerosis group was divided into the low BPV (7.02-9.57) group and the high BPV (>9.57-14.29) group. The non-invasive ambulatory blood pressure monitoring apparatus was used for 24 h blood pressure monitoring, measuring time in the daytime: 6:00-21:59, measuring one time every 30 min; measuring time in the nighttime: 22:00-5:59, measuring one time every 60 min. The dSBP, dDBP, nSBP, nDBP, 24 h SBP, and 24 h DBP were recorded. BPV was expressed as 24 h SCV and 24 h DCV.Results:The dSBP, nSBP, 24 h SBP, 24 h DBP, and 24 h SCV in the carotid atherosclerosis group were significantly higher than those in the pure hypertension group, while the comparison of dDBP, nDBP, and 24 h DCV between the two groups was not statistically significant. The common carotid artery and external carotid artery IMT, and the mean IMT in the high BPV group were significantly higher than those in the low BPV group, and the number of carotid plaques being detected was significantly greater than that in the low BPV group.Conclusions:BPV is involved in the arterial functional and structural changes, resulting in the target organ damage. Detection of carotid IMT is of great significance in evaluating the early vascular damage and predicting the cardiovascular events; therefore, BPV monitoring should be strengthened during the diagnosis and treatment of hypertension.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    by the presence and severity of pulmonary hypertension (PH) assessed by right-heart catheterization in 3 hemodynamically distinct groups: (1) non-PH (mean pulmonary arterial pressure [mPAP]50 mm Hg; median HE Grade 4 (range 3-6), with generalized arterial dilatation and plexiform lesions. CONCLUSIONS...

  17. Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus-infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor

    Directory of Open Access Journals (Sweden)

    Pierangelo Chinello

    2015-03-01

    Full Text Available Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI. We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI.

  18. Acute hemodynamic effects of single-dose sildenafil when added to established bosentan therapy in patients with pulmonary arterial hypertension: results of the COMPASS-1 study.

    Science.gov (United States)

    Gruenig, Ekkehard; Michelakis, Evangelos; Vachiéry, Jean-Luc; Vizza, Carmine Dario; Meyer, F Joachim; Doelberg, Martin; Bach, Doris; Dingemanse, Jasper; Galiè, Nazzareno

    2009-11-01

    This study investigated the acute pharmacodynamic effects of sildenafil in patients with pulmonary arterial hypertension (PAH) and concomitant bosentan treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs. This prospective, open-label, noncomparative, multicenter, phase II study enrolled 45 patients (>or=18 years) with stable PAH (idiopathic, familial, or related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins) and on bosentan treatment for at least 3 months. Patients underwent right heart catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric oxide (iNO) and (b) a single oral dose of sildenafil (25 mg). Mean pulmonary vascular resistance (PVR) decreased from baseline following iNO (-15%; 95% confidence limits: -21%, -8%; P = .0001). A statistically significant decrease from baseline in mean PVR was also observed 60 minutes following sildenafil administration (-15%; 95% confidence limits: -21%, -10%; P < .0001). The reduction in PVR following sildenafil was comparable to that resulting from iNO. There were no unexpected safety findings. The pharmacodynamic effect suggests that addition of sildenafil to bosentan treatment can elicit additional hemodynamic benefits. These data represent a rationale for long-term combination studies with the 2 compounds. PMID:19755415

  19. A Huge Thrombosed Pulmonary Artery Aneurysm without Pulmonary Hypertension in a Patient with Hepatosplenic Schistosomiasis

    Science.gov (United States)

    Abo-Salem, Elsayed S.; Ramadan, Mahmoud M.

    2015-01-01

    Patient: Male, 55 Final Diagnosis: Thrombosed pulmonary artery aneurysm Symptoms: Cough productive • fever • shortness of breath Medication: — Clinical Procedure: Pericardiocentesis Specialty: Cardiology Objective: Rare disease Background: We herein report a case of huge pulmonary artery aneurysm in a 55-year-old male farmer from the Nile delta (Lower-Egypt), mostly due to infestation with Schistosoma mansoni, which is the parasite causing hepatosplenic schistosomiasis. Case Report: This male patient was admitted with a month-long history of progressive shortness of breath, 2-month history of fever, and a cough with mucoid sputum for 10 days. On examination, he had normal temperature and blood pressure, but he had tachypnea, tachycardia, and congested neck veins. Electrocardiography showed multifocal atrial tachycardia and right bundle branch block. Conclusions: The present case is unique in that it shows the presence of a huge pulmonary artery aneurysm despite the absence of pulmonary hypertension. PMID:25746428

  20. Selective increase of the contractile response to endothelin-1 in subcutaneous arteries from patients with essential hypertension

    DEFF Research Database (Denmark)

    Lind, H; Adner, M; Erlinge, D;

    1999-01-01

    arteries from subjects with established essential hypertension with matched controls. Furthermore, with RT-PCR, the occurrence of mRNA for the ETA and ET(B) receptors was shown in the tunica media layer of subcutaneous arteries in controls and hypertensives. The maximum contractile response to endothelin-1...... was significantly higher in the subcutaneous arteries of the hypertensives (by 88% with no change in potency) as compared to controls. The responses to noradrenaline, acetylcholine and potassium chloride did not differ between the groups. This selective increase in the contractile response to......Endothelin-1 has been shown to contribute to basal vascular tone in man. Since endothelin-1 is a potent vasoconstrictor putatively involved in hypertension, we have compared the contractile responses of endothelin-1 and noradrenaline in relation to potassium chloride in subcutaneous resistance...

  1. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael;

    2004-01-01

    In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value...... no CV disease, while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk...... is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass...

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

    Directory of Open Access Journals (Sweden)

    Bernardo RJ

    2014-08-01

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

  3. Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by increased arterial resistance in broilers.

    Science.gov (United States)

    Lorenzoni, A G; Anthony, N B; Wideman, R F

    2008-01-01

    Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance. PMID:18079461

  4. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    Directory of Open Access Journals (Sweden)

    Salvatore Rosanio

    2014-01-01

    Full Text Available This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

  5. [Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia].

    Science.gov (United States)

    Danilov, N M; Matchin, Iu G; Chazova, I E

    2012-01-01

    Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant

  6. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center.

    Science.gov (United States)

    Chin, Kelly Marie; Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando

    2015-09-01

    Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = -0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose. PMID:26401252

  7. Elevated radial arterial augmentation index in hypertensive patients with diastolic dysfunction

    Institute of Scientific and Technical Information of China (English)

    Qiang Zeng; Xiaonan Sun; Li Fan; Xinming Wang; Ping Ye

    2008-01-01

    Objective To investigate the correlation between augmentation index (AI) of the radial artery and diastolic heart function in patients with hypertension.Methods Echocardiographs were obtained for 305 patients with hypertension.AI,pulse wave velocity (PWV) of peripheral arteries and serum pro-brain natriuretic peptide (proBNP) levels were determined.Correlations and receiver operating characteristic (ROC) curves were drawn between AI values and impaired diastolic function.Results AI levels were significantly increased in patients with impaired diastolic function diagnosed by ultrasound.Assessment of diastolic heart function based on proBNP levels revealed that AI and aortic pulse wave velocity were significantly elevated in patients with impaired diastolic function.The operating curve indicated that AI may be a more accurate and efficient index for the evaluation of impaired diastolic function compared to pWV.Correlation analysis also showed that proBNP levels had altered in parallel with changes in AI and PWV.After adjusting for various factors including age,gender,blood pressure and blood lipid,a positive correlation was observed between proBNP and AI with a correlation coefficient of 0.3697 (P =0.003).However,no correlation between proBNP and aortic PWV was seen after adjustment.Conclusions Changes in radial AI levels may reflect parallel changes in diastolic cardiac function in patients with hypertension,suggesting that AI may be utilized as a non-invasive clinical indicator of diastolic heart function.

  8. The importance of echocardiography in diagnostics of idiopathic pulmonary arterial hypertension: A case report

    Directory of Open Access Journals (Sweden)

    Stojković Gabrijela

    2011-01-01

    Full Text Available Introduction. Idiopathic pulmonary arterial hypertension (IPAH is rare and difficult progressive disease with prevalence of approximately 15 cases per million residents, with predominant female cases. Case Outline. A 47-year-old female presented with symptoms and signs of the right heart chambers failure. Over prior seven years the patient had the feeling of suffocation and fatigue when walking, and received treatment for bronchial asthma. Physical examination revealed a marked loud second heart sound over the pulmonary artery. Electrocardiogram: right ventricular hypertrophy. Spirometric (pulmonary capacity test, cardiac perfusion scan and spiral CT scanning excluded secondary pulmonary arterial hypertension. Blood testing for connective tissue diseases and HIV were within normal reference limits. Transthoracic colour Doppler echocardiography demonstrated a mild tricuspid regurgitation with high values of estimated maximal and middle systolic pressure of the right ventricle (135/110 mm Hg, and excluded previous heart disease. Cardiac catheterization confirmed IPAH diagnosis, with systolic right ventricular pressure of 101/47/66 mm Hg and pulmonary capillary pressure of 30/13/10 mm Hg. Basic therapy with sildenafil, nevertheless, considerable limitations of strain tolerance was still present. Conclusion. IPAH is a severe heart disease with non-specific signs and symptoms. Screening for IPAH is transthoracic colour Doppler echocardiography shows high correlation with cardiac catheterization.

  9. Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

    Directory of Open Access Journals (Sweden)

    Ninet Gérard

    2009-09-01

    Full Text Available Abstract A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up.

  10. Renal artery stenosis detection by combined Gates' technique and captopril test in hypertensive patients

    International Nuclear Information System (INIS)

    We studied 11 hypertensive patients by a radionuclide technique using Gates' method with [/sup 99m/Tc]DTPA to investigate the acute effects of captopril on glomerular filtration rate (GFR). Five patients had hypertension with unilateral renal artery stenosis (RAS) angiographically documented and six patients had essential hypertension (EH). Total and split GFR were determined under control conditions and after oral administration of captopril (50 mg). In the patients with RAS, captopril induced a significant decrease of GFR in the stenotic kidneys (from 42.4 +/- 4 to 29.6 +/- 3 ml/min, p less than 0.01), while no changes were observed in the nonstenotic kidneys (from 61.2 +/- 3 to 61.6 +/- 5 ml/min, NS). Total GFR was 103.6 +/- 5 ml/min under control conditions and decreased to 91.8 +/- 6 ml/min after captopril (p less than 0.05). No significant changes of GFR were detected after captopril administration in patients with EH. In a separate group of ten patients with EH, good correlation between 24-hr creatinine clearance and fractional uptake of [/sup 99m/Tc]DTPA was obtained. Good reproducibility of this radionuclide technique was also shown. This study demonstrates that the computed radionuclide GFR determination coupled with the captopril test allows one to unmask angiotensin II-dependent renal function and hemodynamic changes. This technique can be useful in clinical practice for identifying patients with renovascular hypertension

  11. COMBINED ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION AFTER THE STROKE

    Directory of Open Access Journals (Sweden)

    O. A. Ageenkova

    2010-01-01

    Full Text Available Aim. To evaluate influence of the combined therapy with ACE inhibitor (perindopril, diuretic (indapamide and dihydropyridine calcium channel blocker (amlodipine on ambulatory blood pressure (BP monitoring indices and heart rate variability in hypertensive patients during early recovery period of stroke.Material and methods. 39 patients (28 men, 11 women with arterial hypertension of 1-3 degrees during early recovery period after stroke were examined. They received perindopril 10 mg QD, indapamide — 1.5 mg QD. Calcium channel blocker amlodipine (5 mg QD was added in case of insufficient effect of the ACE inhibitor plus diuretic combination.Results. The combined antihypertensive therapy in hypertensive patients after the stroke led to significant decrease of systolic and diastolic BP (by 23.5% and 18.9%, respectively, normalization of BP daily profile (a number of «dippers» enlarged by 42.2%, improvement of the wall vessel rigidity (decrease in pulse wave velocity by 12.9% and heart rhythm variability (increase in SDNN, PNN50 and RMSSD by 7%, 20% and 25%, respectively.Conclusion. Advantages of the combined antihypertensive therapy (ACE inhibitor, diuretic, calcium channel blocker in treatment of hypertensive patients after the stroke are shown.

  12. Individual differences as predictors of dietary patterns among menopausal women with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Maria Gacek

    2014-05-01

    Full Text Available Introduction: The aim of this study was to analyze selected individual determinants of dietary choices, important for etiology and prevention of degenerative cardiovascular disorders, in a group of menopausal women diagnosed with arterial hypertension. Material and methods: The study included a group of 160 women from the Małopolska region, aged between 45 and 60 years and diagnosed with arterial hypertension. A questionnaire assessing the frequency of food product consumption was used, along with standardized psychological tests (GSES, LOT-R, and SWLS. Spearman’s coefficients of rank correlation and the Kruskal-Wallis and Dunn tests were used for statistical analysis. Results: We revealed that higher levels of self-efficacy were associated with more frequent consumption of whole grains, oatmeal, raw vegetables, fruit, semi-skimmed milk, natural yoghurt, marine fish, legume seeds, soy products, nuts, plant oils, and fruit and vegetable juices, as well as with less frequent consumption of whole milk, high-fat cottage cheese, and sweetened carbonated beverages and alcoholic beverages. The levels of optimism and satisfaction with life correlated positively with the consumption frequency of brown rice, whole grains, oatmeal, fruit, marine fish, legumes, soy products, nuts, butter, and fruit juices, and were inversely correlated with the consumption of white bread, high-fat cottage cheese, pork meat and sausages, and sweets and pastries. Conclusions : Postmenopausal women with arterial hypertension who were characterized by lower levels of self-efficacy, optimism, and satisfaction with life made less rational dietary choices which could negatively affect the efficacy of the secondary prevention of cardiovascular degenerative disorders.

  13. Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bessa, Luiz Gustavo Pignataro, E-mail: lgpignataro@ig.com.br; Junqueira, Flávia Pegado; Bandeira, Marcelo Luiz da Silva; Garcia, Marcelo Iorio; Xavier, Sérgio Salles; Lavall, Guilherme; Torres, Diego; Waetge, Daniel [Hospital Universitário Clementino Fraga Filho, Ilha do Fundão, RJ (Brazil)

    2013-10-15

    Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m{sup 2}, and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m{sup 2}, there was a relevant association with the increased percentage of myocardial fibrosis. The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension.

  14. Impact of Whole Body Cryotherapy at -110 °C on Subjects with Arterial Hypertension.

    Science.gov (United States)

    Missmann, M; Himsl, M; Mur, E; Ulmer, H; Marschang, P

    2016-02-01

    Whole body cryotherapy (WBC) in a cryo-chamber as a medical treatment was first established in Japan in the 1980s, later in Central Europe, and is now becoming more popular also in the United States. The exposure to extreme, non-physiological environmental conditions in a cryo-chamber at -110 °C may exceed the normal adaption capacity. The aim of this study was to investigate the effects of WBC on blood pressure (BP) readings in adult subjects with rheumatic disorders and normal or moderately elevated BP. A sample of 23 subjects (8 female, 15 male) which were recruited according to their pathology between the age of 35 and 69 years undergoing 21 WBC applications was divided into three groups: a group of subjects with anti-hypertensive therapy, a group of subjects with mild arterial hypertension without medical treatment, and a normotensive control-group. A total of 483 BP readings were taken immediately before and after each WBC application. The systolic and diastolic BP were recorded, and the mean arterial pressure, and the amplitude of BP were calculated. A statistically significant rise of BP after WBC was found in the whole sample and in the normotensive group. Over the course of time, no significant change of BP behavior was observed, except for normotensive subjects, who showed a wider range in their systolic BP values. Generally accepted exclusion criteria were applied, and in our sample group WBC was safe with respect to unwanted BP alterations for adult subjects under 70 years-regardless of a pre-existing untreated mild or pharmacologically treated arterial hypertension. Greater changes of BP values might infrequently occur, so an individual monitoring of subjects is necessary. PMID:26408646

  15. Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

    International Nuclear Information System (INIS)

    Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m2, and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m2, there was a relevant association with the increased percentage of myocardial fibrosis. The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension

  16. β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension

    OpenAIRE

    Heerkens, Egidius H.J; Quinn, Lisa; Withers, Sarah B.; Heagerty, Anthony M

    2014-01-01

    Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVβ3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, thi...

  17. Optimization of regular medical examination of patients with arterial hypertension and metabolic disorders

    Directory of Open Access Journals (Sweden)

    V.V. Blinova

    2010-06-01

    Full Text Available The scientific work is devoted to examination of 180 patients with arterial hypertension in case of metabolic syndrome during the period of 12 months. By the end of initial examination patients were divided into 3 groups. The first group (72 men and women was regularly checked by cardiologist once in 3 months, the second one (60 patients -once in 6 months, the third group (48 patients was observed once a year. Accordingly regular clinical examination provides more effective conditions for observation and treatment, improvement of health state and hemodynamic indices allowing to cosider the given way of clinical examination as a rational and effective method

  18. COMPARISON OF ENALAPRIL AND PERINDOPRIL IN PATIENTS WITH ARTERIAL HYPERTENSION AND LEFT VENTRICLE SYSTOLIC DYSFUNCTION

    OpenAIRE

    Yu. I. Grinshtein; O. L. Barbarash; D. A. Yakhontov; A. E. Popelysheva; V. V. Shabalin; N. B. Osetrova

    2016-01-01

    Aim. To compare efficacy of enalapril and perindopril in patients with arterial hypertension (HT) and left ventricle systolic dysfunction.Material and methods. Patients (n=51) with HT and left ventricle systolic dysfunction (ejection fraction<45%) were included in the prospective open randomized comparative study. Patients were randomized into 2 groups of therapy with enalapril 10-20 mg BID (n=25) or with perindopril 4-8 mg OD (n=26). Hydrochlorothiazide (12,5-25 mg OD) was added in case o...

  19. Use of a 10-Channel Linear Scanner in the Differential Diagnosis of Arterial Hypertension

    International Nuclear Information System (INIS)

    The need for a simple clinical test for singling out patients suffering from arterial hypertension due to renovascular causes has long been recognized. Over the past year, the authors have been using a linear scintillation scanner with ten detectors in parallel for delineating lesions within the kidney and estimating the rate of renal accumulation of 203Hg-labelled chlormerodrin. With this apparatus one can obtain very satisfactory renal images within two or three minutes after intravenous administration of 100 - 250 mCi of a radioactive drug. Scintigraphic images of both kidneys were obtained at 5, 10, 20, 30, 40, 50 and 60 min after administration of the radioactive compound without supression of the background radioactivity. All data were recorded on magnetic tape to permit subsequent selection of the technical parameters required for the reproduction of an image of optimum contrast and intensity. The pulse integrator included in the instrument was used to assess radioactivity in both kidneys during each scanning. Results were expressed as the ratio of renal radioactivity at a given time (Ct) to renal radioactivity after five minutes (C5); this value was called the renal concentration index (RCI). To distinguish bilateral renal ischaemia from essential arterial hypertension, the RCI of the right kidney (RK) was divided by the RCI of the left kidney (LK), which gave a comparative index for the two kidneys (Icomp.). The authors conclude that the procedure as described could be used as a selective test for arterial hypertension of renovascular origin, since it furnishes an index directly correlated with the individual renal plasma flow and a series of images representative of the regional blood flow in each of the kidneys. As renal concentration of chlormerodrin requires both good renal blood flow and tubular cell efficiency, in cases of unilateral tubular necrosis results will be obtained similar to those for cases of unilateral renal ischaemia. The authors

  20. SHIFTWORK AS ONE OF RISK FACTORS OF ARTERIAL HYPERTENSION AND METABOLIC DISORDERS

    OpenAIRE

    2015-01-01

    Background. Shiftwork is considered as one of risk factors of arterial hypertension (HT) and metabolic disorders. Aim. To study effects of different types of shift plan on HT and the metabolic disorders development. Material and Methods. 1091 men were included in the study. Patients were split into subgroups according to age (20–29, 30–39, 40–49, 50–59 years old) and shift plan (steady or shiftable work schedule). HT (blood pressure >130/85 mm Hg), abdominal obesity (waist circumference &g...